The ION+EMI Study: Intermittent Oral Naltrexone Enhanced With an Ecological Momentary Intervention for Methamphetamine-using MSM
Phase: PHASE2
Conditions: Methamphetamine Use Disorder
Sponsor: Glenn-Milo Santos

Official Title of the study:  
 
 
 
Intermittent Oral Naltrexone Enhanced With an Ecological Momentary Intervention for 
Methamphetamine-using MSM 
 
 
 
 
 
 
NCT number:  
 
NCT04791969 
 
 
Document Type:  
 
Study Protocol 
 
 
 
Date of the document:  
 
09/30/2024 
 
 

Study Application (Version 1.21)
1.0
General Information
*Enter the full title of your study:
The ION+EMI Study: Intermittent Oral Naltrexone enhanced with an Ecological Momentary 
Intervention for Methamphetamine-using MSM
 
 
*Enter the study alias:
HiNT Study
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this 
study.
 
 
2.0
Add departments
2.1 and Specify Research Location:
Is 
Primary? Department Name
UCSF - 
 - N_CHS-Administration
318006
UCSF - 
 - E_Human Rsch Protection Prog
469026
 
3.0
List the key study personnel: (Note: external and affiliated collaborators who 
are not in the UCSF directory can be identified later in the Qualifications of 
Key Study Personnel section at the end of the form)
3.1 *Please add a Principal Investigator for the study:
 
Santos, Glenn-Milo
Select if applicable
Department Chair
Resident
Fellow
If the Principal Investigator is a Fellow, the name of the Faculty Advisor must be supplied below.
 
3.2 If applicable, please select the Research Staff personnel
 
A) Additional Investigators
Coffin, Phillip O, MD 
 Other Investigator
Matheson, Tim 
 Other Investigator
Vittinghoff, Eric PhD 
 Other Investigator
N

B) Research Support Staff
Balcazar, Andrew L 
 Study Recruiter
Dunham, Alexandrea 
 Clinical Research Associate
Farley, John 
 Study Recruiter
Hoffmann, Thomas, PhD 
 Biostatistician
Ikeda, Janet 
 Study Coordinator
Jan, Fareshta 
 Clinical Research Associate
Parker, Ella 
 Clinical Research Associate
POPE, EMILY R 
 Clinical Research Associate
Tavasieff, Sophia R 
 Study Recruiter
Walker, John 
 Study Nurse
Yuhas, Trent W 
 Clinical Research Associate
3.3 *Please add a Study Contact
 
Ikeda, Janet 
Santos, Glenn-Milo 
The Study Contact(s) will receive all important system notifications along with the Principal 
Investigator. (e.g. The project contact(s) are typically either the Study Coordinator or the Principal 
Investigator themselves).
3.4 If applicable, please add a Faculty Advisor/Mentor:
 
3.5 If applicable, please select the Designated Department Approval(s)
 
Add the name of the individual authorized to approve and sign off on this protocol from your 
Department (e.g. the Department Chair or Dean).
4.0
 
Initial Screening Questions 
Updated April 2020 - Revised Common Rule (January 2018) Compliant / COVID-19 - 
v94
4.1  * 
:
PROJECT SUMMARY  (REQUIRED) Give a brief overview of this project (250 words or less). Tell us 
what this study is about, who is being studied, and what it aims to achieve. If you have an NIH 
Abstract, paste it here (Click on the orange question mark to the right for more detailed instructions):

Methamphetamine (meth) use is very common among men who have sex with men (MSM), 
particularly MSM living with HIV. Meth use among HIV-negative and HIV-positive MSM is up to 13 
and 34 times more prevalent than in the general U.S. adult population, respectively. Meth use is 
independently associated with HIV-related sexual risk behaviors among MSM and can function as 
a barrier to antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) adherence. Thus, 
effective interventions to reduce meth use may also function as an important HIV prevention and 
care intervention by reducing meth-related HIV risk behavior, and optimizing ART and PrEP 
adherence. MSM comprise two-thirds of the new infections in the United States. Despite this 
continued domestic HIV epidemic and the high prevalence of meth use among MSM, few 
interventions have proven efficacious for MSM who use meth. We seek to address this gap by 
evaluating the efficacy of intermittent oral naltrexone enhanced with an ecological momentary 
intervention (ION+EMI) for meth use treatment. Naltrexone, a µ-opioid receptor antagonist, is a 
promising agent for MSM who use meth. Meth is rapidly metabolized to amphetamine in the 
bloodstream and daily naltrexone has shown efficacy in reducing amphetamine urine-positivity 
. Oral naltrexone is inexpensive and has few toxicities, but the standard daily regimen 
and relapse
for naltrexone hampers compliance as patients frequently neglect to take the medication. 
Alternate regimen schedules have been proposed to increase efficacy and expand the population 
that may benefit from this pharmacologic agent. One alternative approach is the targeted 
administration of intermittent oral naltrexone (ION), whereby individuals are instructed to take 
the medication 
 in anticipation of substance use, after exposure to triggers of substance 
as needed
use, or during periods of craving. Administration of naltrexone prior to exposure to amphetamines 
significantly attenuated amphetamine craving in 4 trials. Additionally, emerging evidence 
suggests that ecological momentary interventions (EMI) that respond to in-the-moment contexts 
can lead to positive health behaviors, such as increasing medication dosing. EMI are particularly 
well-suited to enhancing as-needed dosing of naltrexone because anticipation of meth use and 
meth craving in a natural setting changes within a person from moment to moment, and the 
detection of these momentary fluctuations can support the delivery of just-in-time messages to 
encourage medication use to prevent participants from proceeding from craving to meth use. A 
pilot study led by our research team on ION found that meth-using MSM who use at least 1 day 
per week had significantly greater reductions in meth-using days when treated with as-needed 
naltrexone, compared to placebo. Moreover, naltrexone participants had greater reductions in 
serodiscordant receptive anal intercourse and serodiscordant condomless receptive anal 
intercourse, compared to placebo. In the pilot, participants reported taking study drug 64% of the 
days that they craved or anticipated meth use. Participants also completed ecological momentary 
assessments (EMA) with a 74% response rate, indicating that real-time assessments are feasible 
and acceptable. To build on the results of this study and 4 other naltrexone trials, we propose to 
evaluate intermittent naltrexone to treat meth in a phase 2b efficacy trial supplemented by an 
EMA-informed EMI that responds to a participant’s real-time craving levels or anticipated meth 
use to provide in-the-moment medication reminders when participants would most benefit from 
naltrexone. We hypothesize that pairing ION with EMI will further amplify reductions in meth use 
by providing just-in-time reminders for naltrexone to optimize adherence, thereby interrupting 
the progression from craving to meth use.
4.2  
 
* 
:
HUD DEVICE (REQUIRED) 
 
Does this application involve a Humanitarian Use Device (HUD):
No 
Yes, and it includes a research component 
Yes, and it involves clinical care ONLY 
4.3  * 
: 
TYPE OF RESEARCH (REQUIRED) 
(
Select the option that best fits your project Click the orange 
question mark to the right for definitions and guidance):
Biomedical research (including medical records review, biospecimen collection and/or use, 
other healthcare or health outcomes related activities, research database, biospecimen bank, 
or recruitment registry) 
Social, behavioral, educational, and/or public policy research 
Hybrid - includes aspects of BOTH types of research (check this option if your research is 
mainly social/behavioral but also involves specimen collection or blood draws to look at 
biological measures) 
4.4  * 
 
SUBJECT CONTACT: (REQUIRED) Does this study involve 
 contact or interactions with 
ANY
participants:
Yes (including phone, email or web contact) 

No (limited to medical records review, biological specimen analysis, and/or data analysis) 
4.5  
 
* RISK LEVEL: (REQUIRED) What is your estimation of the risk level, including all screening 
:
procedures and study activities
Minimal risk 
Greater than minimal risk 
4.6  * REVIEW LEVEL: (REQUIRED) Requested review level (Click on the orange question mark to the 
right for definitions and guidance):
Full Committee 
Expedited 
Exempt 
4.9  
 
* DATA/SPECIMEN ANALYSIS ONLY: (REQUIRED) Does this study 
 involve records review and
ONLY
/or biospecimen analysis (do not check 'Yes' if this is a registry, research or recruitment database, or 
biospecimen repository):
  Yes  
  No
4.10  
 
* CLINICAL TRIAL: (REQUIRED)
Is this a clinical trial:
According to The World Health Organization (WHO) and the 
International Committee of Medical Journal Editors (ICMJE) a 
clinical trial is:
Any research study that prospectively assigns human participants or 
groups of humans to one or more health-related interventions to 
evaluate the effects on health outcomes.
ICMJE requires 
 of a clinical trial in a public database (such as 
registration
ClinicalTrials.gov) prior to enrollment, for eventual publication of results in 
member biomedical journals.
Public Law 110-85 requires that all investigators who perform 
Guidance: 
an 
 must ensure that the trial is registered on a 
applicable clinical trial
 
.
government web site called ClinicalTrials.gov
 
The FDA requires registration for 'applicable clinical trials,' defined 
as follows:
For any trials of drugs and biologics: controlled clinical investigations, 
other than Phase 1 investigations, of a product subject to FDA 
regulation.
For trials of biomedical devices: controlled trials with health outcomes 
of devices subject to FDA regulation, other than small feasibility 
studies, and pediatric post-market surveillance.
 
 
For additional information on the ClinicalTrials.gov registration process at 
UCSF and the definition of a clinical trial for purposes of registration, visit 
 
the ClinicalTrials.gov section of the UCSF Clinical Research Resource 
HUB.
 

 
 Yes  
 No
 - 'NCT' number for this trial:
Clinical Trial Registration
NCT04791969
4.11  * 
: 
CLINICAL TRIAL PHASE (REQUIRED) Check the applicable phase(s):
Phase 0
Phase 1
Phase 1/2
Phase 2
Phase 2/3
Phase 3
Phase 4
Not Applicable
4.12  
: 
* INVESTIGATOR-INITIATED (REQUIRED) Is this an investigator-initiated study:
 Yes  
 No
 of the 
 to 
The UCSF IRB recommends use
Virtual Regulatory Binder
manage your study.
4.13  * 
 
CORONAVIRUS RESEARCH: (REQUIRED) Does this study involve research on coronaviruses (COVID-
19, SARS, MERS or other):
  Yes  
  No
4.15  
 
*
 
CANCER: (REQUIRED) Does this study involve cancer (e.g., the study involves patients with cancer 
or at risk for cancer, including behavioral research, epidemiological research, public policy research, 
specimen analysis, and chart reviews):
  Yes  
  No
4.16  * 
 
RADIATION EXPOSURE: (REQUIRED) Does your protocol involve any radiation exposure to patients
/subjects 
 from 
 
for 
 purposes (e.g., x-rays, CT-scans, DEXA, CT-
EITHER
standard care OR 
research
guided biopsy, radiation therapy, or nuclear medicine including PET, MUGA or bone scans):
  Yes  
  No
4.17  SCIENTIFIC REVIEW: If this study has undergone scientific or scholarly review, please indicate 
which entity performed the review (check all that apply):
Cancer Center Protocol Review Committee (PRC) (Full approval is required prior to final IRB 
approval for cancer-related protocols.)
CTSI Clinical Research Services (CRS) Advisory Committee
CTSI Consultation Services
Departmental scientific review
Other:
 
* Specify Other: (REQUIRED)

NIDA
4.18  
 
* STEM CELLS: (REQUIRED) 
 
Does this study involve
 
human stem cells (including iPS cells and adult 
stem cells), gametes or embryos:
No 
Yes, and requires IRB and GESCR review 
Yes, and requires GESCR review, but NOT IRB review 
4.19  
 
 
*
 
FINANCIAL INTERESTS: (REQUIRED) Do you or any other responsible personnel (or the spouse, 
 
 
registered domestic partner and/or dependent children thereof) have financial interests related to 
 
this study:
  Yes  
  No
5.0
 Funding
5.1  
 
* FEDERAL FUNDING: (REQUIRED) Is this study currently supported in whole or in part by Federal 
funding, 
, OR has it received 
 Federal funding in the past:
even by a subcontract
ANY
 Yes  
 No
5.2  
 
* 
Is this project linked in any way to the Department of Defense (DoD):
DoD INVOLVEMENT: 
(REQUIRED)
  Yes  
  No
5.3  
 
SPONSORS: Identify all sponsors and provide the funding details. If funding comes from a 
 
Subcontract, please list only the Prime Sponsor:
External Sponsors:
 
View 
Details
Sponsor Name
Sponsor Type
Awardee 
Institution:
Contract 
Type:
Project 
Number 
UCSF 
RAS 
System 
Award 
Number 
("A" + 
6 
digits) 
NIH Natl Institute 
on Drug Abuse 
01 
UCSF 
Grant 
PO549101  
Sponsor Name:
NIH Natl Institute on Drug Abuse 
Sponsor Type:
01 
Sponsor Role:
Funding
CFDA Number:
 
Grant/Contract Number:
DA053171-01A1 
Awardee Institution::
UCSF 
Is Institution the Primary 
Grant Holder:
Yes 
Contract Type:
Grant 
Project Number:
PO549101 

UCSF RAS System Award 
Number ("A" + 6 digits):
 
Grant Number for Studies Not 
Funded thru UCSF:
 
Grant Title:
The ION+EMI Study: Intermittent Oral Naltrexone 
enhanced with an Ecological Momentary Intervention for 
Methamphetamine-using MSM 
PI Name:
(If PI is not the same as 
identified on the study.)
Glenn-Milo Santos 
Explain Any Significant 
Discrepancy:
 
Other Funding Sources and Unfunded Research - Gift, Program, 
Departmental or other Internal Funding (check all that apply):
Funded by gift (specify source below)
Funded by UCSF or UC-wide program (specify source below)
Specific departmental funding (specify source below)
Unfunded (miscellaneous departmental funding)
Unfunded student project
6.0
 Sites, Programs, Resources, and External IRB Review
6.1    
  
 (check all that apply): 
 UCSF AND AFFILIATED SITES
*
(REQUIRED)  
UCSF Benioff Children's Hospital Oakland (BCHO)
UCSF Cancer Center Berkeley
UCSF Cancer Center San Mateo
UCSF China Basin clinics and facilities
UCSF Helen Diller Family Comprehensive Cancer Center
UCSF Langley Porter Psychiatric Institute (LPPI)
UCSF Medical Center at Mission Bay (Benioff Children's Hospital, the Betty Irene Moore 
Women's Hospital, Bakar Cancer Hospital, or outpatient clinics)
UCSF Mount Zion
UCSF Parnassus (Moffitt-Long hospital, dental clinics or other outpatient clinics)
UCSF Other Sites (including Laurel Heights and all the other sites outside the main hospitals 
and clinics)
Fresno - UCSF Fresno OR Community Medical Center (CMC)
Gladstone Institutes
Institute on Aging (IOA)
Jewish Home
SF Dept of Public Health (DPH)
SF VA Medical Center (SF VAMC)
Vitalant (formerly Blood Centers of the Pacific and Blood Systems Research Institute)
Zuckerberg San Francisco General (ZSFG)
Research involving the SFDPH: SFDPH sites and clinics has some 
special requirements, including adherence to the SFDPH HIPAA 
, involvement of an
Policy
 SFDPH-approved investigator, 
and inclusion of a signed 
. Your 
SFDPH Research Proposal Approval
submission will be returned to you if it does not include this form.
6.2  
At what locations will study visits and activities occur:
LOCATIONS: 

Study visits will occur at 25 Van Ness Ave., Suite #500, San Francisco, CA. 94102
6.3  
Will any study procedures or tests be conducted off-site by non-UCSF 
OFF-SITE PROCEDURES: 
personnel:
 Yes  
 No
Please identify which procedures may be done off-site:
Study activities will take place at 25 Van Ness Ave., Suite #500.  These activities include 
screening, enrollment, and follow-up visits that include survey administration, urine tests, safety 
labs, sweat patches and HIV tests.
6.4  RESEARCH PROGRAMS: Check any UCSF research programs this study is associated with:
Cancer Center
Center for AIDS Prevention Sciences (CAPS)
Global Health Sciences
Immune Tolerance Network (ITN)
Neurosciences Clinical Research Unit (NCRU)
Osher Center
Positive Health Program
6.5  * CTSI CRS SERVICES: (REQUIRED) Will this study be carried out at one of the UCSF Clinical Research 
 units or utilize 
:
Services (CRS)
CRS services
  Yes  
  No
6.6  * MULTI-CENTER TRIAL: (REQUIRED) Is this a multi-center or multi-site research trial:
By 
' we mean a study where the protocol is developed 
'multi-center trial
by an lead investigator, an industry sponsor, consortium, a disease-group, 
etc.,and multiple sites across the nation or in different countries participate 
in the trial. The local sites do not have any control over the design of the 
protocol.
  Yes  
  No
6.8  OTHER SITE TYPES: Check all the other types of sites not affiliated with UCSF with which you are 
cooperating or collaborating on this project:
Do NOT check any boxes below if this is a multi-center clinical 
trial, UCSF is just one of the sites, and neither UCSF nor one of its 
faculty-linked affiliates (SF VAMC, Gladstone, ZSFG) are the 
coordinating center.
Other UC Campus
Other institution
Other community-based site
Foreign Country
Sovereign Native American nation (e.g. Navajo Nation, Oglala Sioux Tribe, Havasupai, etc.)

6.11  * OUTSIDE RELIANCES: (REQUIRED) Are any of the collaborating sites requesting to rely on UCSF's 
IRB:
  Yes  
  No
6.14  * RELYING ON AN EXTERNAL IRB: (REQUIRED) Does this application include a request to rely on an 
external IRB (a central IRB (other than the NCI CIRB) or an external IRB (other UC campus, 
commercial, or institutional):
  Yes  
  No
7.0
 Outside Site Information
7.1  
 
Outside Site Information
If you have more than 10 sites to add, list the outside sites in the 
Outside Sites List document and upload it in the Other Study 
Documents section of the Initial Review Submission Packet form. 
Any sites requesting to rely on UCSF's IRB must be listed below. 
Click "Add a new row" to enter information for a site. Click it again to add a second site again to 
add a third site, a fourth site, etc.
Outside Site Information
Non-UCSF affiliated site information:
Site name:
University of Texas, Health Science Center
Contact name:
Diane Santa Maria
Email:
Diane.M.Santa Maria@uth.tmc.edu
Phone:
713.500.2002
For Federally-funded studies only, corresponding FWA#:
#00000667
 research at this site will be reviewed by:
* The
The non-affiliated site's IRB or a private IRB 
The non-affiliated site is requesting UCSF to be the IRB of 

record for this study 
The non-affiliated site is not engaged in the human subjects 
research and has provided a letter of support 
If the other site's IRB approval letter is available now, attach it to 
the application.  If the IRB approval letter is not yet available, 
submit it once you receive it. 
  
  Or, if the other site is 
 in human subjects 
 
not engaged
research, attach the letter of support to your application.
Outside Site Information
Non-UCSF affiliated site information:
Site name:
Universty of Oklahoma, Health Science Center
Contact name:
Michael Businelle
Email:
Michael-Businelle@OUHSC.edu
Phone:
405-271-8001 x50460
For Federally-funded studies only, corresponding FWA#:
#00007961
 research at this site will be reviewed by:
* The
The non-affiliated site's IRB or a private IRB 
The non-affiliated site is requesting UCSF to be the IRB of 
record for this study 
The non-affiliated site is not engaged in the human subjects 
research and has provided a letter of support 
If the other site's IRB approval letter is available now, attach it to 
the application.  If the IRB approval letter is not yet available, 
submit it once you receive it. 
  
  Or, if the other site is 
 in human subjects 
 
not engaged
research, attach the letter of support to your application.
8.0
 Research Plan and Procedures

1.  
2.  
3.  
1.  
2.  
3.  
8.1  
Describe the hypothesis or what the study hopes to prove:
HYPOTHESIS: 
Our Hypotheses are:
Targeted Intermittent Oral Naltrexone (ION) will significantly reduce meth use, as 
determined by the proportion of meth-positive urine tests, compared to placebo.
Targeted ION will significantly reduce meth-associated sexual risk behavior, as determined 
by the audio computer assisted self-interview (ACASI) data and sexual risk behavior data, 
compared to placebo.
Targeted ION will significantly increase PrEP adherence among HIV-negative participants 
and ART adherence among participants living with HIV, as determined by drug levels and 
viral load testing; and sexual risk behavior data accounting for PrEP use and viral 
suppression, compared to placebo.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.2  
List the specific aims:
AIMS: 
Our Aims are:
To determine the efficacy of ION vs. placebo in reducing meth use, as determined by the 
proportion of meth-positive urine tests
To determine the efficacy of ION vs. placebo in reducing meth-associated sexual risk 
behaviors
To determine the efficacy of ION vs. placebo in increasing PrEP adherence among HIV-
negative participants and ART adherence among participants living with HIV
8.3  
Briefly describe the study design (e.g., observational, interventional, randomized, placebo-
DESIGN: 
controlled, blinded, cross-over, cross-sectional, longitudinal, pharmacokinetic, etc.):  
This is a double-blind, placebo-controlled phase 2b trial in which 60 MSM who 
 
Research Design:
use meth will be randomly assigned (2:1) to receive 12 weeks of as-needed intermittent oral 
naltrexone 50 mg enhanced with an EMA-informed EMI platform, or receive as-needed placebo 
with EMA-informed EMI. The 12-week treatment period is consistent with other pharmacotherapy 

trials for substance use disorders.
 The proposed sample size is also consistent 
66,85,124,125,142,143
with other phase 2b trials for substance use treatment.
 Upon enrollment, participants 
66,125,144
will complete daily EMA assessments and weekly visits for behavioral surveys and urine testing 
for meth metabolites, study drug dispensing and counseling for substance use. Safety laboratory 
assessments and vital signs will be completed monthly. Efficacy (Specific Aims 1-3) will be 
assessed upon trial completion as measured by proportion meth-positive urine samples; PrEP and 
ART adherence by drug levels and viral load testing; and sexual risk behavior data accounting for 
PrEP use and viral suppression. 
8.4  
 Briefly provide the background and significance of this study (e.g. 
BACKGROUND AND SIGNIFICANCE:
 
why is this study needed) (space limit: one half page):
If this is a first in humans study, please summarize the safety data from 
the animal studies. For pediatric drug or device studies, please identify if 
this is the first study in pediatric populations.  
Meth use is a major public health issue among cisgender men who have sex 
with men (MSM). National HIV Behavioral Surveillance (NHBS) data indicate that among HIV-
negative and HIV-positive MSM, meth use is up to 13 and 34 times more prevalent than in the 
general adult population.
 Meth use is associated with significant morbidity and mortality.
 
1,2
3,4
Meth is a highly addictive drug with serious medical, societal, and economic consequences.
 In 
5-16
San Francisco, there has been a steady increase across all meth indicators (treatment 
admissions, emergency department visits, inpatient hospitalizations, and deaths) since 2009.17
Cisgender MSM are disproportionately impacted by HIV, accounting for 66% and 
74% of new infections in the US and San Francisco, respectively.
 The rate of new infections 
18,19
in cisgender MSM in San Francisco is estimated at 369 infections per 100,000, compared to 36 
per 100,000 overall.
 It is imperative to develop more evidence-based HIV-prevention 
19
interventions for MSM, including MSM who use meth.
Meth use is independently associated with HIV risk behaviors. NHBS data show 
that meth use before or during sex are common for MSM. In NHBS, 66% of meth users reported 
having sex while under the influence of meth.
 The acute effects of meth (e.g., altered 
20
cognition, impairment of judgment, and increased sexual desire and confidence) are postulated to 
contribute to risk-taking behaviors.
 A myriad of psychosocial factors (e.g., cognitive escape, 
21-23
impulsivity, expectancies) are believed to mediate the association between meth use and sexual 
risk behaviors.
 Additionally, for racial and ethnic minority MSM, co-occurring psychosocial 
24,25
and clinical morbidities, as well as the intersection of stigmas, are also associated with greater 
meth use and sexual risk.
 Furthermore, the late-night bar, club, and circuit-party (weekend-
26-29
long dance events) settings frequented by MSM are environments conducive to both meth use 
and meeting sex partners.30-32
In systematic reviews of studies among MSM, 
 analyses of meth use 
event-level
immediately before or during sexual episodes 
 indicate that it is 
consistently
independently associated with increased likelihood of having condomless sex in that 
event.33,34 
 assessments of meth use provide a precise temporal link between these 
Event-level
substances and HIV risk, and provide stronger evidence for causality.
 Meth use is 
33,34
independently associated with condomless anal intercourse, multiple partners, increased duration 
of sex, anonymous partners, sex in a public sex venue, and exchanging money or drugs for sex.35
-40
Meth use has been independently associated with new HIV infections.
 In a 
40-42
longitudinal study of 4,295 HIV-negative MSM from six metropolitan areas, 16% of incident HIV 
infections were attributable to meth use.
 Moreover, meth use is associated with syphilis 
43
infection and other sexually transmitted diseases, which in turn increase HIV risk.
 Injection 
44-46
of meth has been documented across 60 countries globally and people who inject meth may be at 
heightened risk for HIV because of the potential for HIV transmission from sexual and injecting 
risk behaviors.
 
47 Among people living with HIV, meth use is associated with poor health 
.
 
  Meth may function as a 
outcomes due to lower antiretroviral therapy adherence 48,49 50
barrier to the ability of HIV-positive MSM to adhere to ART by increasing their forgetfulness, or 
reducing their ability to maintain routine.
 Frequent meth use is also associated with two-fold 
46
increased odds for primary drug resistance to any class of HIV drugs.
 
51 Among HIV-negative 

individuals using pre-exposure prophylaxis (PrEP) to prevent HIV infection, meth use 
Moreover, meth use was 
has also been reported as a barrier to PrEP adherence.52 
associated with sub-optimal (less than 4 doses per week) PrEP adherence based on drug level 
testing data.
 Because meth use is associated with high-risk sexual behavior, lower PrEP and 
53
ART use, HIV seroconversion, STD incidence, and drug-resistant HIV, data strongly support that 
meth use plays an important role in perpetuating the U.S. HIV epidemic. ADDIN EN.CITE.DATA 5,3
 Therefore, effective interventions that reduce meth use will also likely have 
2,40,44,46,51,54-63
profound effects in reducing HIV risk via reductions of meth-associated sexual risk behaviors.
Pharmacotherapy for substance use disorders treatment can play an important 
role in addressing HIV. For example, efficacious, FDA-approved pharmacologic interventions 
that treat opioid use disorders have also been demonstrated to reduce HIV transmission.
 
64,65 Res
earch conducted by our group among MSM with severe meth use disorders has also demonstrated 
that reductions in meth use from pharmacologic treatment can lead to successful reductions in 
meth-associated sexual behaviors.66
         There are no FDA-approved medications for meth use disorders. Furthermore, 
there are no effective pharmacologic strategies for meth-using MSM without severe use 
disorders.67,68 Although a sizable proportion of meth users are episodic users who do not have 
severe use disorders,
 pharmacologic studies have focused on individuals with severe use 
69,70
disorders.
 While some behavioral interventions for MSM reduce substance use and HIV risk 
70,71
behaviors,
 they may benefit from adjuvant pharmacologic agents.
68,72,73
74,75
            Naltrexone is a promising agent for meth use that blocks the rewarding effects 
of meth. Administration of meth enhances release of mRNA precursors for endogenous opioids 
that bind to μ-opioid receptors and increase extracellular dopamine levels.
 Naltrexone 
76-78
competitively blocks endogenous opioids from activating μ-opioid receptors
 in the nucleus 
79
accumbens and ventral tegmental area, which mediate dopamine release. Thus, the opioid 
antagonism by naltrexone decreases the activity of the dopamine reward pathways, tempering 
the positive neurobiological effects of meth.78-81
Naltrexone is effective in attenuating the positive subjective effects of meth 
intoxication—including quality of “high”, craving, and euphoria, supporting efficacy 
among current meth users.82-87 Meth is rapidly metabolized to amphetamine in the 
 and administration of oral naltrexone prior to amphetamine exposure significantly 
bloodstream
reduced both the subjective effects of amphetamine and craving for amphetamine among healthy 
and amphetamine-dependent humans in laboratory studies.
 Additionally, oral naltrexone was 
87,88
associated with reductions in both craving and subjective response to meth, and also significantly 
reduced the association 
 craving and subjective response to meth after meth 
between
administration.
 Four double-blind, placebo-controlled naltrexone trials have observed efficacy 
89,90
on subjective effects and craving.87-89,91
Daily 
 
oral naltrexone has significantly reduced amphetamine-positive urine 
Naltrexon
samples and craving in a randomized controlled trial with a 12 week follow-up. 
e significantly reduced relapse measured via urinalyses for amphetamine use and resulted in a 
“reasonably strong” to “strong” effect size (d=0.5) in a trial among 80 amphetamine-dependent 
heterosexual adults.
 The study reported that naltrexone produced reductions in both craving 
91
and reward sufficient to counteract the reinforcing effect of amphetamine, even in the setting of 
modest adherence (63% had naltrexone adherence of at least 66% during follow-up).91 Given 
naltrexone’s efficacy in blocking the rewarding effects of meth/amphetamine and relapse to use,92
 naltrexone may be a promising option to attenuate craving and reduce episodic meth use on an 
 Naltrexone is well-tolerated and has no known significant drug interactions 
“as-needed” basis.
with meth.
 Naltrexone has few serious side effects and no known abuse potential or 
79,91,93-96
sexual side effects.94,95,97-100
            Oral naltrexone’s pharmacokinetic properties support its promise for 
intermittent targeted administration (i.e., during craving). Naltrexone’s activity is believed to 
be due to both the parent compound and the 6-β-naltrexol metabolite.
 Naltrexone reaches peak 
97
plasma levels within 1 hour of oral administration. The mean elimination half-life for naltrexone 
and 6-β-naltrexol are 5 and 13 hours, respectively.
 Naltrexone also has high affinity for 
97,101,102
the μ-opioid receptor (Ki = 2.5 ± 0.21 nM) and a single 50mg dose can block μ-opioid receptors 
 raising the possibility that dosing 1-2 days prior to anticipated meth use 
for up to 72 hours,103
may be effective. With its rapid onset and long duration of action, naltrexone is well-suited for 
intermittent dosing.

            Targeted administration of intermittent oral naltrexone (ION) on an “as-
needed” basis has shown promise in treating substance use and reducing sexual risk 
behaviors.104-108  A pilot study of targeted ION conducted by our group found that meth-using 
MSM who used at least 1 day per week had significantly greater reductions in meth-using days 
when treated with as-needed naltrexone, compared to placebo (RR = 0.78).
 In the same 
109
study, we found that targeted ION participants had greater reductions in serodiscordant receptive 
anal intercourse (RR = 0.15) and serodiscordant condomless receptive anal intercourse (RR = 
0.11), compared to placebo.
 In other substance using populations, ION dosing has also been 
109
shown to be feasible, acceptable and efficacious.
 For example, ION administered after a 
106,110
period of daily dosing significantly reduced heavy-drinking relapse.
 
108 In another trial by 
Kranzler, et al. (n=163), men assigned to 
 showed significantly greater reductions in mean 
ION
drinks per day, and in number of drinks during drinking days, compared to those assigned to daily
 Therefore, there is mounting 
naltrexone administration, 
 placebo, or intermittent placebo.
daily
106
evidence that ION is a promising dosing strategy to treat substance use and sexual risk 
behaviors.  
          Meth use is associated with factors that fluctuate from day to day—such as 
craving, stress, and mood—antecedents which have all been shown to have high 
 
predictive validity for meth use.111 Day-level antecedent fluctuations detected in ecological 
 Santa Maria (Co-I) and 
momentary assessments (EMA) strongly predict subsequent drug use.
Santos (PI) observed that days with high drug craving were significantly associated with a 47.2 
increased odds of using drugs within the same day.
 Meta-analysis of EMA data on drug craving 
112
also observed consistent linkages between drug craving and drug use.
 Furthermore, using EMA 
113
to monitor these antecedents is ideal because the predictive validity of these antecedents on 
meth use decreases as the time of assessment becomes more distant (i.e., as the assessments of 
antecedents happen further away from real-time).
 Therefore, monitoring these antecedents 
111
with EMA in real time would enable more precise identification of moments when the risk of meth 
use is high.  Monitoring daily variations of these antecedents in EMA decreases recall bias and 
(i.
increases data validity because the measurements occur near real-time, and in natural settings 
e., environments outside research laboratories or clinics).
 Furthermore, we have 
112,114-116
demonstrated the feasibility, acceptability and validity of EMA approaches among MSM who use 
meth in pharmacotherapy,
 diverse samples of substance-using MSM
 and other 
116,117
118
marginalized populations.112,115
Targeted administration of ION could be enhanced by just-in-time reminders 
that leverage EMA monitoring for craving or perceived likelihood of using meth. Ecologica
l momentary approaches can be extended to dynamically send (“push”) information based on 
EMA responses that indicate heightened risk for meth use, with what is referred to as EMA-
informed ecological momentary interventions (EMI). Specifically, EMA detection of meth use 
antecedents such as craving can be used to trigger just-in-time EMI adherence reminders to 
encourage naltrexone use during these moments when individuals are at heightened risk for meth 
use and when they could most benefit from the effect of this pharmacologic intervention via its 
. The use of EMA-informed EMI to increase adherence is 
effects on reducing meth craving
supported by the Health Belief Model (HBM), which posits that individuals are more likely to 
engage behavior change when they are made aware of their perceived susceptibility to a health 
issue (e.g., high susceptibility for meth use when antecedents identified by EMA), perceive benefit 
from a behavior (e.g., efficacy of taking ION during moments when antecedents are identified); 
and when they receive prompts or cues to act/engage in behaviors (e.g., prompts from EMI to 
take ION cued at moments of susceptibility).
 In systematic reviews, the majority of 
119,120
adherence interventions (78%) informed by HBM have significantly increased medication 
adherence across multiple health conditions.121
EMA-informed EMI procedures are feasible and acceptable among marginalized 
populations. Dr. Santa Maria (Co-I) and Dr. Businelle (consultant) have successfully enrolled 
and completed EMA-informed EMI studies, with high EMA completion rates and high EMI receipt 
rates (>80% across the MY-RID and Smart-T studies), among homeless youth and 
socioeconomically disadvantaged adults from urban safety-net hospitals. 
 Furthermore, 
122,123
participants in Drs. Santa Maria and Businelle’s studies consistently report liking EMA-informed 
EMI and report high study satisfaction rates, indicating high acceptability.122,123
             MSM who use meth in pharmacotherapy trials will likely benefit from just-in-
time adherence reminders because this population often cite forgetfulness as a primary 
reason they have difficulty taking their medications for meth treatment. The most 
common reason for non-adherence reported by participants in three pharmacologic studies of oral 
medications among MSM who use meth conducted by our group (cumulative sample n=180) was f
 People living with HIV also cite forgetfulness because of their meth use as 
orgetfulness.66,124,125

TABLE 1: RELEVANT STUDIES BY RESEARCH TEAM
PHARMACOTHERAPY FOR MSM WHO 
USE SUBSTANCES
(n)
Duration
Retention
# 
Screened
(Enroll. ra
tio)
Harness Study (Intermittent Oral Kudzu)
120
12 weeks
Ongoing
Ongoing
a barrier to HIV treatment.
 Adherence text reminders are efficacious in increasing medication 
50
adherence; data from the EPIC study by Vittinghoff (Co-I) and colleagues, for example, observed 
that text message reminders on PrEP adherence significantly increase PrEP use.
 Similarly, a 
126
meta-analysis of text messaging adherence reminders demonstrated efficacy in increasing 
medication adherence across chronic diseases.
 Given the fact that antecedents that predict 
127
meth use such as craving vary daily and can be reduced by naltrexone, but meth users often 
forget to take their oral medications, utilizing EMA-informed EMI adherence reminders is a 
promising approach to enhance naltrexone treatment of meth use. EMI can provide just-in-time 
reminders to facilitate adherence during moments when individuals would most benefit from the 
pharmacologic intervention. Despite the potential of EMI to support adherence to targeted 
pharmacotherapy, to our knowledge, there have been no trials that have evaluated the efficacy of 
treating meth use with targeted intermittent oral naltrexone enhanced with EMI adherence 
reminders.
8.5  
Briefly summarize any preliminary studies relevant to your proposed 
PRELIMINARY STUDIES: 
research 
:
(space limit: one half page)
  
Preliminary Studies: Numerous studies published by Dr. Santos and the collaborating research 
team involving MSM have informed the proposed research.
 The study team 
58,66,70,71,124,149-156
has successfully enrolled multiple cohorts of non-treatment seeking MSM in non-abstinence–
based pharmacologic and behavioral trials with excellent participation in study visits, procedures, 
and retention rates.
 Our previous research has also demonstrated that reductions in 
66,124,125,150
substance use can result in parallel reductions in HIV sexual risk behaviors.
 
 lists 
66,71 Table 1
relevant studies conducted by our group.
 The 
 Project iN (intermittent naltrexone) study:
current proposal logically builds on this pilot study establishing the feasibility, acceptability and 
 of ION among 30 meth-using MSM without severe use disorders
ClinicalTrials.gov 
tolerability
 (
Identifier: NCT01723384). Preliminary data were extremely promising with a 61% screen to 
enroll rate, 95% retention rate and 93% study completion rate, suggesting that conducting a 
larger efficacy study on ION is 
 among meth-using MSM without severe use disorders. In 
feasible
addition, MSM in the trial reported high 
: most were satisfied
acceptability for the study procedures
/highly satisfied with the study (76%), were very likely to participate in a future study (71%), 
and were very likely to recommend the study to a friend (71%). No one in the study had stopped 
medications because of adverse events, suggesting that this intervention is 
 in this 
tolerable
population. This pilot was not powered to detect efficacy. We recognize the need for caution when 
interpreting results of pilot studies for hypothesis testing, as well as the controversy on 
estimating treatment effects from pilot studies.
 Nevertheless, specifying and testing 
157,158
analyses on meth use and sexual behaviors in the context of our pilot work is an important step 
in determining the applicability of our measures and analyses for a larger formal efficacy trial. In e
, we noted a point estimate consistent with a 
xploratory, intention-to-treat (ITT) analyses
protective 
 in favor of naltrexone, compared to placebo, on meth use (RR = 0.82).
 While 
signal
109
this was not statistically significant, we recognize that in small trials such as ours, type II error (i.
e., false negatives) is a bigger concern due to small samples sizes, as opposed to type I error (i.
e., false positives).
 Hence, we interpret this result with caution. The study also found that 
158
meth-using MSM who used at least 1 day per week had significantly greater reductions in meth-
using days when treated with ION, compared to placebo in a sub-group analysis (RR = 0.78).
 
109
Finally, we also found that ION participants had greater reductions in serodiscordant receptive 
anal intercourse (RR = 0.15) and serodiscordant condomless receptive anal intercourse (RR = 
0.11), compared to placebo.
 Participants also reported taking study drug 64% of the days that 
109
they craved meth or anticipated meth use. While this study drug compliance rate is better relative 
to our other pharmacotherapy trials with daily dosing, it still indicates a gap in compliance that 
can be enhanced with an adherence intervention, such as EMI. Hence, these findings support the 
 
f
 of ION to treat MSM who use meth and 
easibility, acceptability, tolerability, and potential utility
reduce HIV-related risks.
 

Curb the Line (Lorcaserin)
22
12 weeks
86%
56 (40%)
Say When (Intermittent Oral Naltrexone) 
120
12 weeks
89%
269 (45%)
Trex Study (Intramuscular Naltrexone) 144
100
12 weeks
90%
194 (52%)
Project iN (Intermittent Oral Naltrexone
) 
109
30
8 weeks
95%
49 (61%)*
BUMP Study 1 (Bupropion
)
124
30
12 weeks
90%
54 (56%)
BUMP Study 2 (Mirtazapine
)
66
60
12 weeks
95%
212 (56%)
BUMP Study 3 (Aripiprazole
)
125
90
12 weeks
83%
375 (24%)
M 2.0 Study (Mirtazapine)
120
48 weeks
94%
241 (50%)
Observational/Ecologic Momentary Studies on Substan
ce Use
(n)
Duration
SUPreMe Study ( ubstance se and 
EP among 
SM)
S
U
Pr
M
250
1 year
Digital Divide Ecological Momentary Study118
45
7 days
SAMBA: timulants lcohol 
omentary ehavioral ssessmen
S
A
M
B
A
ts
263
14 days
Project Youth HIV Risk Estimator Development
66
21 days
Smart-T EMI Study
59
3 weeks
 
8.6  
Is this a treatment study, i.e. does this study intend to provide treatment 
* TREATMENT PROTOCOL: 
to individuals with a medical or psychological condition: (REQUIRED)
 Yes  
 No
8.7  
 Does this study involve any procedures, lab tests or imaging studies that 
* BILLABLE PROCEDURES:
have a CPT code and could be billable to patients, their insurance, Medi-Cal, Medicare, or any other 
entity (answer 'Yes' even if the study is going to pay for all the procedures): (REQUIRED)
  Yes  
  No
, send 
If you are not sure if your study involves billable procedures
an email to the 
 for help 
UCSF Office of Clinical Research (OCR)
answering this question.
8.8  
Types of research activities that will be carried out. Check all that 
 COMMON RESEARCH ACTIVITIES: 
*
apply and describe in more detail in the 'Procedures / Methods' section: (REQUIRED)

Interviews, questionnaires, surveys
Educational or cognitive tests
Focus groups
Social media-based research activities
Observation
Fitness tests or other exertion activities
Use of mobile health apps or other apps
Collection of data from wearable tech such as Fitbit, Apple Watch, Garmin, motion actigraphs, 
etc.)
Non-invasive imaging or testing (MRI, EEG, pulse oximetry, etc.)
Imaging procedures or treatment procedures that involve radiation (x-rays, CT scans, CT-
guided biopsies, DEXA scans, MUGA or PET scan)
Administration of contrast agent
Randomization to one intervention versus another
Use of placebo
Biopsy conducted solely for research purposes
Sham surgical procedure
None of the above
8.9  
PROCEDURES / METHODS: 
* 
(REQUIRED)
For clinical research, list all study procedures, tests and treatments 
required for this study, including when and how often they will be 
performed. If there are no clinical procedures, describe the research 
activities.
 
If some of the activities would occur even if the person were not in the 
study, as in the case of treatment or tests performed for diagnostic 
purposes, clearly differentiate between those activities that will be 
done solely for research purposes and those that are happening as 
part of routine care.
 
Examples may include:
additional scans outside standard clinical diagnosis or monitoring
additional biopsies to collect tissue for research
extra clinic visits
extra lab tests not required for clinical care
If you have a procedure table, attach it to the submission with your 
other study documents.
               Study Procedures:  Potential participants will be asked brief eligibility screening 
questions in person or over the phone after providing verbal consent. Potential participants will 
provide informed consent and be screened for eligibility during the pre-enrollment screening visit. 
The schedule for the study procedures is shown in 
.
Table 3
 
Participants will be compensated for their time at each visit and in responding to daily ecological 
momentary messages (up to a total of $421). Participants will receive $50 for the 2 in-office 
screening visits ($20 at Screen 1 and $30 at Screen 2), $15 each for in-office run-in visits 1 and 
2, $40 for in-office enrollment, $15 for remote weekly visits (1-3, 5-7, and 9-11), $15 for in-
office weekly visits (4, 8, 12), $40 for in-office week 4 (month 1) and week 8 (month 2) visits, 
and $50 for week 12 (month 3). In addition, they will receive $0.40 for each day that they 
complete the daily EMA series throughout the 12-week treatment period (up to $36).  Participants 
will be paid by cash, visa gift cards, or by paypal.  
 
Participants could receive a gift card ($10) for partial screening visits. For any snowball referral 
that has completed a screening visit, the participant who referred the new participant will receive 

$10. If the new participant enrolls in the study, the participant who referred the new participant 
will receive $40.
 
We will follow the UCSF’s COVID-19 policy for clinical 
 
COVID-19 Precautions:
research, which prioritizes the health and safety of UCSF's patients, participants, staff, trainees, 
and community. It also aligns with State of California laws, local public health directives, NIH 
policies, and other institutional guidance on COVID-19.
 Additionally, as a precaution prior to 
163
each study visit, participants will be asked whether they have any of the current symptoms 
 
indicated by the Centers for Disease Control and Prevention for COVID-19 in the past two weeks 
for screening visits, or since the last visit for active participants.
 Those experiencing symptoms 
164
regardless of severity will be referred to free public testing sites by staff
 and visits will be 
165
rescheduled as appropriate (i.e., until receipt of COVID-19 test result to rule out infection). 
Temperature checks to screen for fevers will also be used among participants upon arrival at our 
research site. Additionally, we will require staff and patients to wear personal protective 
equipment (PPE) during study visits and promote six-feet social distancing. The Center on 
Substance Use and Health (CSUH) at 25 Van Ness Ave is implementing a COVID-19 safety 
standard operating procedures (SOP) that includes infection control such as using EPA List N: 
Disinfectants for Use Against SARS-CoV-2 and 30-minutes of fluorescent lights to kill air-borne 
viruses
1-3, 5- 7 and 9-11) for the 
.  We will also conduct the following weekly visits remotely (
safety of our participants and staff. We will incorporate additional guidelines as policies and 
precautions for COVID-19 evolves or COVID-19 diminishes. 
 
Recruitment Procedures: Potential participants will be recruited through multiple 
sources. Our recruitment team has a long record of successful recruitment of individuals with 
meth use. We will recruit from bars and clubs, needle exchanges, street corners, HIV and other 
clinics, and social service programs. We will post advertisements, including website (www.
hintstudy.org), local newspapers, billboards, and public transit posters. We will also recruit 
participants that screen ineligible for our other ongoing studies.
Study Site: Study activities will take place at the Center on Substance Use and Health 
(CSUH) of the San Francisco Department of Public Health (SFDPH), a well-established clinical trial 
site located at 25 Van Ness Avenue. Dr. Santos has a joint appointment as a Senior Research 
Scientist at SFDPH. He has conducted research at this field site since 2008. The site is centrally 
located near multiple transit lines with convenient access for residents of multiple neighborhoods 
with high rates of alcohol use. As noted above, we have had remarkable success recruiting and 
retaining meth users at this location. Study staff have access to both SFDPH resources (see LOS 
from SFDPH Director Colfax) and UCSF resources as described in the Facilities section. The paired 
effort of these institutions has proven highly effective in both research and clinical care in San 
Francisco.
Randomization: Randomization (2:1 for ION versus placebo) will occur using double-
blind, block randomization. Assignment of two-thirds of participants to the ION arm was chosen 
to improve our ability to 1) examine whether EMI leads to greater ION adherence, and reductions 
Thi
in meth use, and 2) enhance our ability to  detect adverse events in the active treatment arm. 
s ratio was also selected with the knowledge that it has a negligible impact on the study’s 
minimum detectable treatment effects, compared to a 1:1 allocation (i.e., the difference in the 
detectable treatment effects between the 1:1 and 2:1 allocation ratios were minor across all 
primary outcomes), while retaining a stable size for placebo, in the event that some participants 
are lost to follow-up. The study biostatistician will generate a random allocation sequence list with 
treatment assignments associated with order of enrollment, using randomly permuted blocks with 
randomly selected block sizes 3 and 6. To ensure balance by HIV-status, allocation will also be 
stratified by HIV serostatus. To mask the randomized allocation sequence, the statistician will 
provide this stratified list to the study pharmacist.
Study medication: The Safeway Compounding Pharmacy, which currently prepares our 
study drug for our ongoing clinical trials, will provide the study drug kits for the proposed trial. 
Drugs are over-capsuled in a locking capsule to ensure the same appearance across all study 
arms and maintain double-blind. Study medications will be dispensed by the study clinician in 
MEMS
 capped bottles with dosing instructions, date of dispensing, prescribing clinician, a 24-
®
hour telephone study phone number for medical emergencies (415-356-8980), and advisements 
against drug combinations. 
Participants will be trained on targeted 
Training on targeted dosing:  
medication dosing during enrollment and be provided an instructional leaflet for reference. They 
will be instructed to take 1 tablet when they believe that meth use risk is high or when meth use 
is imminent.
 Participants will be given seven 50mg tablets per week and will be instructed to 
109
not exceed 1 tablet every 24 hours.
 Based on concordance in adherence measures (self-
109
report, pill count, and electronic monitoring) in our 
 trials, we are confident that very 
double-blind
little, if any, sharing of study medications is occurring between 
 participants.
 As a 
blinded
168,169
precaution, participants will be briefed about the importance of not sharing medications.

 
                
 
EMA and EMI Cognitive Interviewing Methodology:  The study team will 
 
beta test
the EMI and then conduct cognitive interviews with 10 MSM who use meth in individual sessions 
using a semi-structured interview guide with open-ended questions to explore their perceived 
understanding of EMA questions and EMI prompts and explore problems with wording and 
language. Consistent with prior studies, we will read the content of EMA and EMI messages and 
ask participants to paraphrase the meaning to the messages. Interviews will also ask participants 
to reflect, comment, and elaborate on the meaning and relevance of, and discuss potential 
sources of confusion from the messages and prompts. We will also include explicit probes about 
relevant HBM constructs being conveyed in EMI prompts. Specifically, we will ask participants 
whether the EMI prompt successfully inform them of their perceived susceptibility to meth use, 
the benefits of taking the medication at this moment of susceptibility, and whether the EMI 
 Using Framework analysis, the 
prompt provides a clear cue to action to take their medication.
study team will synthesize concerns and make modifications to address problems identified 
related to the following areas: vague language, confusing questions and response options, 
variable interpretation of terms, and misinterpretation of EMI recommendations. Framework 
analysis is well-suited for analyzing the specific questions posed in the cognitive interviews.170,171
 
The EMA and EMI platform with be programmed and 
EMA and EMI procedures: 
administered using the HIPAA-compliant platform of PiLR Health (MEI Research), which is capable 
of deploying text messaging prompts that pull and push content to participants that are timed, 
randomized, and triggered by specific logic and skip programs based on real-time data. Hence, 
this platform can be tailored to suit the needs of the study to collect EMA data and administer 
EMA-informed EMI adherence reminders. We already utilize PiLR Health’ platform to develop and 
implement automated surveys and dynamic prompts on our ongoing studies. For this study, 
participants in both arms will receive EMA surveys for data collection using established methods 
consistent with EMA protocols that involve daily assessments at set and random time periods.112,1
 Consistent with our other studies, EMA surveys will capture data on the drug use 
14,115
antecedents (craving, mood, and stress) previously shown to predict drug use in the literature 
and our prior research
; data on recent meth use
; and data on study 
116,118,172-176
112,116,118
drug use
 
Each day, participants will receive a series of up to five EMA surveys that 
116 (Table 3). 
monitor these constructs near real-time (note: the number of random surveys may be adjusted 
based on the findings on the number of questions threshold of acceptability from the cognitive 
interviews). One survey will be consistently deployed during the time when the participant begins 
their day; up to four additional surveys will be deployed at random times throughout the same 
day.
 Participants will also receive additional prompts to take their medication during 
112,114,115
days when they have not yet taken their study medication, but have reported high levels of 
craving, stress, or bad mood (i.e., EMA-informed EMI adherence reminders). Participants will 
receive stipends for completing the EMA surveys and the stipends will be escalated over follow-up 
to maintain engagement and response rate. In final ACASI surveys, we will assess the 
acceptability of lowered or no stipends for the EMA surveys, as well as alternative incentives that 
have been deemed acceptable in other clinical settings (e.g., raffle drawings177, ultra-low 
 
magnitude reinforcers178). 
  All participants will receive standard HIV risk reduction 
HIV testing and counseling:
counseling at enrollment and month 3 with HIV rapid antibody test and pooled viral load (HIV-
negative participants) and CD4 and viral load testing (participants living with HIV).
 
179
Participants with positive rapid tests will have confirmatory HIV Ab/Ag and HIV viral load testing 
conducted, and will receive HIV counseling and referrals to HIV service providers. Participants 
newly diagnosed with HIV at screen will be referred to community resources and will be contacted 
for rescreening in the subsequent month, consistent with our prior studies among MSM who use 
meth.
  
66,124,125
 This study’s aim is to determine the 
Computer based counseling for substance use:
efficacy of pharmacologic interventions to reduce meth use, thus we will utilize a background of 
relatively brief counseling that would be feasible in a clinical setting with limited resources: a 
computerized version of cognitive behavioral therapy, CBT4CBT, previously demonstrated to 
efficaciously reduce substance use. CBT4CBT may be less likely to mask a clinically significant 
effect, in keeping with the "Lessons Learned" paper from the NIDA-sponsored Cocaine Rapid 
Evaluation Screening Trials (CREST), in which it was recommended that clinical trials of 
pharmacologic agents for substance use utilize less intensive, but standardized, psychosocial 
counseling interventions.
 In addition, intensive interventions among people who use meth 
176
have had low completion rates,
 suggesting that multiple lengthy counseling sessions may be 
68
unacceptable to many who may otherwise enroll in the trial. While intensive counseling 

interventions (e.g., 1.5 hours of group counseling thrice weekly) have been associated with 
reduced substance use, these results have not been validated outside of research, and 
interventions have not been adopted widely in clinical practice.68,177
             
 Blood specimens will be collected for monthly safety lab 
Medical safety measures:
assessments via venipuncture by clinicians or research associates with phlebotomy training. 
Medications taken 30 days prior to enrollment and while enrolled in the study will be documented 
on a concomitant medications form. Adverse events (AE) detection: AEs and concomitant 
medications will be elicited from participants verbally and documented weekly. As previously 
noted, participants will be given the 24-hour phone number to reach the study clinician in 
emergencies. Clinicians will follow the “Division of AIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events” and UCSF IRB reporting guidelines.168 Safety monitoring will 
include the assessment, follow-up, and reporting of clinical/serious AEs.
           
 During screen 1 and 2,  run- in 1 and run- in 2 visits and 
 Opioid and Fentanyl testing: 
enrollment visit, and follow-up monthly visits at Month 1, 2, and 3. We will be testing participants 
for opiates through urine samples using the 11 panel Reditest from Redwood Toxicology 
(Abbott).  We will also use the rapid response single drug Fentanyl strip in urine from BTNX to 
make sure that substances purchased on the streets  were not cut with fentanyl which also 
interacts with the study drug naltrexone.  Participants will be provided with a Study guide that 
includes a list of drugs that contain opioids and reminded during the weekly visits that the study 
drug naltrexone interacts with opioids and can cause withdrawl symptoms.  Participants will be 
tested for opioid and fentanyl at Screen 1 & 2, Enrollment, week 4 (month 1), week 8 (month 2) 
and week 12 (month 3) visits.   
         Sweat Testing: We will utilize tamper evident sweat patches (PharmChem, Inc., Fort 
Worth, Texas) that absorb perspiration 24 hours a day, for up to 10 days of continuous wear.
 
187
These patches will be tested for the presence of meth and meth metabolites, using testing 
procedures approved by the FDA since 1995.
 PharmChek patch enzyme immunoassays to 
187
detect meth in sweat have been found to have 85% sensitivity and a 93% specificity rates, 
compared to gas chromatography-mass spectrometry.
 At screening visits, we will affix patches 
188
on all participants. These patches have a semi-permeable membrane to allow oxygen, carbon 
dioxide and water vapor to pass through the patch, keeping the skin underneath sterile and 
healthy. We will replace the used patch worn since the prior visit and send those used patches for 
meth testing to PharmChem’s laboratories. These patches will retain meth and meth metabolites 
for any use during the period it was worn. Hence, we anticipate no gaps in the window of 
detection for meth use. 
            
 Among HIV-negative participants on PrEP and HIV-positive 
PrEP and ART adherence:
participants on ART, we will collect  20 ml. urine samples and test
using a Urine 
 drug levels 
Tenofovir immunoassay  and RNA viral load from blood samples collected at baseline and monthly 
follow-up visits. For PrEP, good adherence will be defined as having tenofovir-diphosphate (TFV-
 1500 ng/ml
DP) concentration of
, which has been classified as evidence of consistent dosing.182,18
 Good ART adherence among participants living with HIV will be defined as having 
3 184
undetectable HIV viral load below 50 copies/ml. 
 The study will collect self-reported adherence via weekly 
Study drug adherence:
modified TLFB assessments, similar to prior targeted naltrexone studies
 and via EMA for all 
106,209
participants.
 Pill counts at weekly visits will also assess adherence. 
 will be used to 
109
MEMS caps
track medication adherence daily 
; each cap opening is recorded as an 
for as-treated analyses
event in real time. MEMS have been shown to be reliable for adherence monitoring and have been 
used in our studies.
 
66,124 109
 summarizes the data source and 
Behavioral survey measurements:  Table 4
collection schedule for the study measures. Standardized and validated behavioral measures42,201
 will be assessed using audio computer administered surveys (ACASI) and EMA to 
,202,210-213
minimize underreporting of risk activities and standardize data collection.
 To minimize 
201,202
potential social desirability bias, staff will not access to data during the trial.
Retention and Termination: We will remind participants of their upcoming visits in 
advance by phone. Missed visits will be rescheduled. Participants will not be provided with ION 
after study completion. Participants will be provided with referrals for primary care providers, 
including providers who accept uninsured patients.
CPHR’s Community Consulting Group (CCG) is a panel of community 
Community Input: 
stakeholders, treatment advocates, and service providers from a range of community-based 
organizations. Members of the CCG includes individuals with expertise on meth, and other 
individuals familiar with the unique needs of MSM who use meth. The CCG meets quarterly and 

  TABLE 3. Study Procedures                             Visit:
S
E
W
M 1, 2
M 3
 
Informed consent
X
 
 
 
 
 
Safety lab assessment
X
 
 
X
X
 
Rapid HIV test* or CD4
X
 
 
 
X
 
HIV risk reduction counseling
X
 
 
 
X
 
Complete medical history, physical exam, SCID
X
 
 
 
 
 
Vital signs, weight
X
X
 
X
X
 
Symptom-driven physical exam
 
X
 
 
X
 
Intermittent Medication Training
 
X
 
 
 
 
Training for EMA
 
X
 
 
 
 
Randomization
 
X
 
 
 
 
11-panel Urine testing for opiates, substance use and fentanyl
X
X
 
x
x
 
Urine testing for meth metabolites
 
 
x
 
 
 
Audio Computer Assisted Survey Instrument (ACASI)
 
X
X
X
X
 
Adverse event assessment
 
 
X
X
X
 
Medical Management Counseling
 
X
X
 
 
 
PrEP ART adherence by drug levels (HIV-),  viral load (HIV+)
 
X
 
X
x
 
Study drug MEMS adherence monitoring
 
X
X
X
X
 
*Confirmatory tests will be performed for reactive tests. S=Screening, E=Enrollment visit
/Baseline, W=weekly, M = Month (M 3 = Final visit),
has a long history of partnership with our unit, providing input on community perceptions, 
preferences and priorities and is modelled after other research community advisory boards (e.g., 
the Community Advisory Board in the Center for AIDS Prevention Studies at UCSF).
 
214
Additionally, CCG members play an important advisory function in protocol design to maximize 
enrollment (e.g., identify outreach venues, clarify study risks) and retention (e.g., problem-solve 
barriers to engagement), help identify resources for participants, and help disseminate findings. Fi
nally, we will work with the CCG to develop additional COVID-19 safety precautions and 
  
incorporate guidelines in ways that also meet the needs of study participants.
 
 

TABLE 4: SUMMARY OF MEASURES
Data Source
Schedule
PRIMARY PREDICTOR VARIABLE
Trial arm (ION+EMI, placebo+EMI)
Randomization
En
OUTCOME VARIABLES
Primary biologic outcome
Urine samples:  negative vs. positive for meth
Urine samples
En, Wkly
PrEP* and ART adherence
Lab specimens
En, M 1-3,
Behavioral outcomes201,202
Total # of sexual partners, by partner HIV status; number of 
partners using Pre-Exposure Prophylaxis (PrEP); # of partners 
with undetectable viral load
ACASI
En, M 1-3,
Total # of condomless sex acts on/off PrEP/ART, by partner HIV 
status, PrEP status and viral load status
ACASI
En,  M 1-3,
Reported days/episodes meth use
 timeline follow-back
116
ACASI; EMA
En,  W, M 1-3,
Other substance use (opioids, alcohol, cocaine, marijuana, 
ecstasy, gamma-hydroxybutyrate, etc.)
ACASI;
En,  M 1-3
Injecting behaviors: needle-sharing, sharing works
ACASI
En,  M 1-3
 
 
 
 
8.10  
: To what extent, if any, do the planned research procedures differ 
STANDARD CLINICAL PRACTICE
from the care that people would otherwise receive at this institution or the study site if not being 
done locally:
 
All participants will receive substance use counseling and psychotherapy for reducing 
methamphetamine use disorder.  There is no FDA approval to use oral Naltrexone for reducing 
meth use disorder.  This differs from the care that people would otherwise receive at the 
institution. 
8.11  
List all questionnaires, surveys, interview, or focus group guides that will be used for 
INSTRUMENTS: 
this study:
Table #4 provides a summary of the study measures:
 

Substance use treatment (outside study)
ACASI
En,  M 1-3
Barratt's Impulsivity Scale 186
ACASI
En,  M 1-3
Substance use antecedences: Brief Substance Use Craving
;  
172
Visual Analog Scale Craving Scores
; Daily Craving
; 
173
174
Affect, Mood 
; Sexual Excitation Scale/Sexual Inhibition 
175
short form 
, Perceived Stress Scale 
, EMA Risk 
187
176
Antecedents 197
ACASI;
EMA
En, W, M 1-3, 
Daily
 Additional covariates 
 
 
Demographics (age, race, education, income)
ACASI
En
Brief Symptom Inventory
, Severity of Dependence
204
205
ACASI
En, M 1-3,
Study Drug, MEMs and EMA adherence
Timing of pill via MEMs cap openings
MEMS Caps
Daily
Adherence, AIDS Clinical Trials Group measure
; SR
206
109
ACASI; EMA
Mon 1-3; 
Daily
Completion rate of EMA, receipt of EMI prompts
EMA data
Daily
  Safety outcomes
Adverse events (including symptoms & exam findings)207
SR; Clinician
En, M 1-3
Safety laboratory assessments207
Lab specimens
Scr,  M 1-3
  Trial process measures
 
 
Number persons pre-screened, screened, enrolled, retained
Visit database
Ongoing
Perception of EMI effects on HBM constructs
  
119,120
ACASI
M 3
Notes: Scr= screening;     En=enrollment/baseline; Wk=Weekly; M=Month; SR=Self Report;
Attach any unpublished instruments in the 'Other Study Documents' 
section of the Initial Review Submission Packet form after 
completing the study application. Published instruments should 
NOT be attached.
8.12  
Are you drawing any blood or collecting other biosamples (e.g. tissue, 
* BIOSPECIMEN COLLECTION: 
buccal swabs, urine, saliva, hair, etc.) for analysis under this protocol and/or storage for future 
research: (REQUIRED)

 Yes  
 No
Could this study generate genetic data that may be broadly shared (e.g., submitted to 
* 
NIH in compliance with Genomic Data Sharing (GDS)/Genome-Wide Association 
 requirements): 
Studies (GWAS)
(REQUIRED)
  Yes  
  No
Please check the Resource Sharing Plan section of your funding 
notice. You will not be able to share the data as required by your 
funding agency if the consent form doesn't include the required 
language.
8.13  
Briefly summarize the methods and types of analyses that will be 
STATISTICAL METHODS: 
performed:
We will use generalized estimating equations (GEE) to estimate treatment effects on 
repeated study outcomes. Primary analyses will be by intention-to-treat (ITT). In prior trials, we 
had excellent visit retention and study completion. Nonetheless, in this high-risk population, 
missing data may be encountered.
 We will conduct sensitivity analyses imputing all 
215,216
missing urine samples as positive, adjusting for baseline correlates of missingness, and using 
inverse probability of censoring weights.
 
217
Specific Aim 1: To determine the efficacy of ION vs. placebo in reducing meth use, as 
As in our prior trial, a GEE Poisson 
determined by the proportion of meth-positive urine tests. 
model with robust standard errors will be used to compare weekly urine test results by treatment 
assignment; this provides easier-to-interpret risk-ratios
 rather than odds-ratios. The 
218
treatment effect of ION vs. placebo will be modeled as linearly increasing and summarized by the 
between-group difference in means at 12 weeks, net of any baseline difference.  Minimum 
 Based on the prior trial (93% retention with an 8-
Detectable Effects (MDEs) with sample size: 
week follow-up), we estimate that 
 at 12 weeks, and within-
80% of participants will be retained
subject correlation will be 0.45. Under these assumptions, the study sample will have 80% power 
in 2-sided tests with a type-I error rate of 5% to detect net between-group differences in the 
reduction in sweat patch positivity of ~14.5 percentage points. In the Project iN study, we have 
observed reductions on meth use between 18%-22% among the ION arm, compared to placebo, 
in ITT and sub-group analyses.
 Therefore, we believe that the reductions in meth use we are 
109
powered to detect in this aim are reasonable to anticipate. 
, we will also 
In sensitivity analyses
evaluate between-group differences on changes in: 1) any meth-positive samples or self-report of 
meth use in timeline follow back; and 2) meth positivity from self-report only. Concordance of the 
urine testing, and self-reported measures will be examined using weighted Kappa and 
correlations. We recognize that meth use is a stigmatize behavior that may be underreported. 
Hence, in the event of discrepancies between urine results and timeline follow back data on meth 
use, we will treat the urine test results as the gold standard. Additionally, we will analyze 
participant’s perception of whether the EMI prompts had effects on various HBM constructs and 
explore whether these moderate treatment effects on meth use.119,120
Specific Aim 2: To determine the efficacy of ION vs. placebo in reducing meth-
 We will use GEE Poisson models with robust standard errors to 
associated sexual risk behaviors.
assess evidence that the intervention reduces HIV risk behaviors, including number of sex 
partners, number of sex partners with whom meth is used and episodes of condomless sex with 
serodiscordant partners. 
 Using data from our prior trial on baseline means, within-subject 
 MDEs: 
correlation, and over-dispersion, we estimate that the study sample of 60 participants will have 
80% power to detect ~46% net reductions in the numbers of sexual partners, ~67% reductions 
in partners with whom meth is used, and ~52% reductions in episodes of condomless sex with 
serodiscordant partners at 12 weeks. In our Project iN study, we have observed statistically 
significant reductions on sexual risk outcomes ranging between 85%-89% among the treatment 
arm, compared to placebo.
 Therefore, given the results from the prior trial, we believe that the 
109
reductions we are powered to detect in this aim are reasonable to anticipate. In sensitivity 
, we will examine how PrEP use and viral suppression status of participants and their 
analyses
partners (partner data assessed via self-reported egocentric data collection from participants)
  
219
modify treatment effects on sexual risk behaviors. We will also examine whether there is 
evidence of effect modification depending on whether both the study participant and partner, the 

participant only, the partner only, or neither the participant nor the partner used a biomedical 
HIV prevention tool (PrEP or ART).219
Specific Aim 3: To determine the efficacy of ION vs. placebo in increasing PrEP 
adherence among HIV-negative participants and ART adherence among participants living with 
 We will use GEE Poisson 
HIV, as measured by serum drug-levels and viral suppression rates.
models with robust standard errors to assess evidence that the intervention increases PrEP and 
ART adherence. 
Using the assumptions for loss to follow-up from Project iN for Aim 1, we 
 MDEs:  
estimate that the study sample of 60 participants will have 80% power to detect 10-19 
percentage point increases in PrEP/ART adherence, depending on within-subject correlations and 
adherence levels in the reference group.126,220
Exploratory Aims Analyses: To assess evidence for whether EMI plausibly contributes 
, we will assess the temporal association of EMA responses, receipt of 
to reductions in meth use
EMI, and taking ION or placebo, and assess whether the degree of the efficiency of this pathway 
moderates between-group differences in urine positivity, under the hypothesis that ION will be 
most effective among the most responsive participants. To assess long-term treatment effects of 
we will evaluate efficacy at 3 months post-treatment for the primary aim 
ION versus placebo, 
outcomes, using methods described above. 
We will 
As-treated analyses with MEMs data: 
conduct as-treated analyses, using cumulative adherence, calculated as the number of MEMs 
openings between baseline and the day of each urine test, divided by the length of that interval in 
days, as a time-dependent covariate in a log-link model for urine positivity, controlling for the 
placebo effects of adherence. Quadratic terms were used for adherence in this model to account 
for non-linearity.
Sex as a Biological Variable: Not applicable. All participants will be cisgender MSM, 
though we will conduct additional exploratory analyses to examine whether effects vary by other 
important variables including age and race/ethnicity. Additionally, given the differences in co-
morbid psychosocial and clinical characteristics between racial/ethnic minority MSM versus non-
minority MSM who use meth,
 we will explore whether treatment effects for racial/ethnic 
26-29
minority MSM are modified by co-morbidities.
8.14  
List only the 5-10 most relevant references (a separate bibliography can be attached 
REFERENCES: 
 
for reference purposes if this study involves novel approaches, agents, or an emerging technology 
that the IRB may not be familiar with):
1) Centers for Disease Control and Prevention. HIV Infection Risk, Prevention, and Testing 
Behaviors among Men Who Have Sex With Men—National HIV Behavioral Surveillance, 20 U.S. 
Cities, 2014. . HIV Surveillance Special Report 15 2016.
2) Shoptaw S, Peck J, Reback CJ, Rotheram-Fuller E. Psychiatric and substance dependence 
comorbidities, sexually transmitted diseases, and risk behaviors among methamphetamine-
dependent gay and bisexual men seeking outpatient drug abuse treatment. J Psychoactive Drugs 
2003;35 Suppl 1:161
3) Herbeck DM, Brecht ML, Pham AZ. Racial/ethnic differences in health status and morbidity 
among adults who use methamphetamine. Psychol Health Med 2013;18:262-74.
4) Reback CJ, Fletcher JB, Swendeman D. Associations between Sociodemographic Characteristics 
and Sexual Risk Behaviors among Methamphetamine-using Men who Have Sex with Men. Subst 
Use Misuse 2018;53:1826-33.
5) Mimiaga MJ, Reisner SL, Fontaine YM, et al. Walking the line: stimulant use during sex and HIV 
risk behavior among Black urban MSM. Drug Alcohol Depend 2010;110:30-7.
6) Li MJ, Okafor CN, Gorbach PM, Shoptaw S. Intersecting burdens: Homophobic victimization, 
unstable housing, and methamphetamine use in a cohort of men of color who have sex with men. 
Drug Alcohol Depend 2018;192:179-85.
7) Storholm ED, Volk JE, Marcus JL, Silverberg MJ, Satre DD. Risk Perception, Sexual Behaviors, 
and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study. 
Prev Sci 2017;18:737-47.
8) Hojilla JC, Vlahov D, Glidden DV, et al. Skating on thin ice: stimulant use and sub-optimal 
adherence to HIV pre-exposure prophylaxis. Journal of the International AIDS Society 2018;21:
e25103.

9) Jayaram-Lindstrom N, Hammarberg A, Beck O, Franck J. Naltrexone for the treatment of 
amphetamine dependence: a randomized, placebo-controlled trial. Am J Psychiatry 2008;165:
1442-8.
10.) King AC, de Wit H, McNamara PJ, Cao D. Rewarding, stimulant, and sedative alcohol 
responses and relationship to future binge drinking. Arch Gen Psychiatry 2011;68:389-99.
11.) O'Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and 
coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry 1992;49:
881-7.
12.) Volpicelli JR, Rhines KC, Rhines JS, Volpicelli LA, Alterman AI, O'Brien CP. Naltrexone and 
alcohol dependence. Role of subject compliance. Arch Gen Psychiatry 1997;54:737-42.
13) Galloway GP, Singleton EG, The Methamphetamine Treatment Project Corporate A. How long 
does craving predict use of methamphetamine? Assessment of use one to seven weeks after the 
assessment of craving: Craving and ongoing methamphetamine use. Subst Abuse 2009;1:63-79.
14.) Santa Maria D, Padhye N, Yang Y, et al. Drug use patterns and predictors among homeless 
youth: Results of an ecological momentary assessment. Am J Drug Alcohol Abuse 2018;44:551-
60.
9.0
 Biospecimen Collection and/or Bank Administration
9.1  
(check all that apply): 
TYPE OF SPECIMENS 
* 
(REQUIRED)
Blood (provide amount below)
Tissue (describe below)
Other type of biospecimen, such as sputum, cerebrospinal fluid, buccal swabs, etc. (describe 
below)
Existing/archival materials (name source below)
Briefly describe the types of biospecimens that will be collected. Provide the 
amount of blood, if applicable. For leftover/existing/archival material, 
identify the source:
Urine samples will be collected for methamphetamine and other substance use 
metabolites.  Sweat patches will be collected for methamphetamine, methamphetamine 
metabolites and other substance use metabolites.   Among HIV-negative participants on PrEP and 
HIV-positive participants on ART, we will test for drug level concentration and RNA viral load from 
5 ml. blood samples.
 
9.3  
(check all that apply): 
SPECIMENS ARE: 
* 
(REQUIRED)
Leftover specimens from a clinical diagnostic or therapeutic procedure
Specimens collected for research purposes only (including extra samples taken during a 
clinical procedure)
Other
9.4  
 
: Will any specimens or portions of specimens be retained after the study is 
* FUTURE SPECIMEN USE
over for possible use in future research studies: (REQUIRED)
  Yes  
  No
9.6  
Indicate where specimens will ultimately be stored: 
 SPECIMEN DESTINATION: 
*
(REQUIRED)
Indicate where specimens will be sent if they will not 
Outside Entities: 
remain at UCSF (choose at least one; check all that apply):

Cooperative group bank
NIH
Other university or collaborator
Industry sponsor
Other
N/A - all specimens will remain at UCSF
Specify to what institution, cooperative group, or company specimens will 
be transferred:
San Francisco Department of Public Health
: If specimens will remain at UCSF, in what kind of 
Internal Storage
facility will they reside (choose at least one; check all that apply):
UCSF repository/bank being established under this protocol
Existing UCSF specimen repository/bank with IRB approval
National cooperative group bank housed at UCSF
Other location at UCSF (please describe)
N/A - no specimens will be retained at UCSF facilities
9.7  
Will direct identifiers be associated with 
SPECIMENS SENT OUTSIDE UCSF - IDENTIFIABILITY: 
specimens or shared with other researchers and/or outside entities:
Yes 
No 
N/A - Specimens will not be shared with others 
10.0
 Drugs and Devices
10.1  
Are you 
 any drugs and/or biologics that are either 
* DRUGS AND/OR BIOLOGICS: 
STUDYING
approved or unapproved: (REQUIRED)
 Yes  
 No
If you have questions about FDA requirements for drug or device 
research, you can send an 
to request a consult.
email 
10.2  
List the drugs or biologics that will be studied. In the drug details 
LIST THE DRUGS OR BIOLOGICS: 
screen you will be asked questions such as: 
Whether the drug or biologic is FDA approved
If the drug or biologic will be provided at no cost
If an IND is necessary, the IND number, and who holds the IND
If the drug or biologic is FDA approved and an IND is not required, the rationale for the 
decision
If the 
 
 is dispensing the drug or biologic (required unless a 
Investigational Drug Service (IDS)
 is obtained from the IDS)
waiver
Please see the 
 for more details about the use of drugs and biologics in research, 
UCSF IRB website
  
including the 
.
IND Decision Worksheet  
 If the sponsor’s protocol does 
Verification of IND numbers:
not list the IND number, you must submit documentation from the sponsor or FDA identifying the 
IND number for this study. Attach this documentation in the Other Study Documents section of the 
  
Initial Review Submission Packet.  If you have any correspondence from the FDA or 
sponsor regarding this drug or biologic, please attach it to the application.

View 
Details
Drug Name
FDA Approved
A new drug or 
a new use of 
an already 
approved 
drug:
IND Number
Trade Drug 
Name:
NALTREXONE 
HYDROCHLORIDE
Generic Drug 
Name:
NALTREXONE 
HYDROCHLORIDE
Investigational 
Drug Name:
Yes 
Yes 
 
Trade Drug Name:
NALTREXONE HYDROCHLORIDE 
Generic Drug Name:
NALTREXONE HYDROCHLORIDE 
Investigational Drug Name:
 
Identify the name of the 
manufacturer or source of 
investigational drug/biologic:
ReVia  
Is the drug supplied at no cost?
No  
Is the Drug FDA Approved:
Yes  
Is this a new drug or a new 
use of an already approved 
drug
Yes  
Is an IND necessary
No  
IND Number
 
Who holds the IND:
N/A  
IND details:
 
If FDA Approved and an IND is 
not required, Please provide a 
rationale for exemption:
This study meets exemption criteria under 21CFR312.2: the
investigator is not intending to report the study in support 
of a
new indication or change in advertising; there is no 
significant
increase in risk in this study population and it uses the 
same dose
and route as FDA-approved; the study will comply with IRB 
and
informed consent requirements; and the investigator has no
disqualifications. We have submitted the UCSF IND Decision 
worksheet in other study documents.  
Are you currently using this 
IND in another research 
project?
No  
If yes, list the IRB Number(s):
 
Will the investigational 
pharmacy be dispensing?
No  
If the source is not a FDA 
licensed facility, provide details 
regarding the purity, quality, 
stability and sterility of the 
investigational drug/biologic:
 
10.3  
: Are you 
 any medical devices, in vitro diagnostics, or assays that are 
* MEDICAL DEVICES
STUDYING
 
either approved or unapproved:(REQUIRED)
  Yes  
  No

If you have questions about FDA requirements for drug or device 
research, you can send an email to request a consult.
10.6  
Is this an expanded access or compassionate use protocol, meaning the 
* EXPANDED ACCESS: 
primary purpose is to diagnose, monitor or treat a patient's condition, rather than the collection of 
safety and efficacy data of the experimental agent: (REQUIRED)
  Yes  
  No
11.0
 Sample Size and Eligibility Criteria
11.1  
 
How many people will you enroll:
ENROLLMENT TARGET: 
60
 If there are multiple participant groups, indicate how many people will be 
in each group:
The ION+EMI study will enroll 60 participants in the double-blinded placebo controlled clinical trial 
where 40  participants will receive Intermittent Oral Naltrexone and 20 participants will receive 
placebo. 
11.3  
Explain how and why the number of people was chosen. For multi-site 
SAMPLE SIZE JUSTIFICATION: 
studies, this is referring to the number that will be enrolled across all sites:
For the phase 2b clinical trail, a sample size of 60 was selected to provide 80% power in 
2 - s i d e d  
t e s t s  
w i t h  
a  
t y p e - I
error rate of 5% to detect between a 18-22% reduction of meth use among the ION arm, 
compared to placebo, in ITT and sub-group analyses. We hypothesized on pharmacologic grounds 
that 
oral 
naltrexone 
will 
reach 
full 
efficacy 
against 
meth 
use
almost immediately; accordingly we expect treatment-control differences to be approximately 
constant over the 12 weeks of the trial. Based on the prior trial (93% retention), we estimate that 
90% of participants will be retained at 12 weeks. Under these assumptions, the minimum 
detectable effects for our outcomes are calculated as follows:
Specific Aim 1: To determine the efficacy of ION vs. placebo in reducing meth use, as 
As in our prior trial, a GEE 
determined by the proportion of meth-positive sweat patch tests. 
Poisson model with robust standard errors will be used to compare weekly urine test results by 
treatment assignment; this provides easier-to-interpret risk-ratios
 rather than odds-ratios. 
218
The treatment effect of ION vs. placebo will be modeled as linearly increasing and summarized by 
the between-group difference in means at 12 weeks, net of any baseline difference.  Minimum 
 Based on the prior trial (93% retention with an 8-
Detectable Effects (MDEs) with sample size: 
week follow-up), we estimate that 
 at 12 weeks, and within-
90% of participants will be retained
subject correlation will be 0.45. Under these assumptions, the study sample of 60 participants will 
have 80% power in 2-sided tests with a type-I error rate of 5% to detect net between-group 
differences in the reduction in urine  positivity of ~24 percentage points, equivalent to a relative 
rate reduction of 32%. We have observed similar reductions on meth use in ITT and sub-group 
analyses in prior trials.
 Therefore, we believe that the reductions in meth use we are powered 
109
to detect in this aim are reasonable to anticipate.  
, we will also evaluate 
In sensitivity analyses
between-group differences on changes in: 1) any meth-positive samples or self-report of meth 
use in timeline follow back; and 2) meth positivity from self-report only. Concordance of the urine 
testing, and self-reported measures will be examined using weighted Kappa and correlations. We 
recognize that meth use is a stigmatize behavior that may be underreported. Hence, in the event 
of discrepancies between urine test results and timeline follow back data on meth use, we will 
treat the urine test results as the gold standard. Additionally, we will analyze participant’s 
perception of whether the EMI prompts had effects on various HBM constructs and explore 
whether these moderate treatment effects on meth use.119,120
Specific Aim 2: To determine the efficacy of ION vs. placebo in reducing meth-associated 
 We will use GEE Poisson models with robust standard errors to assess 
sexual risk behaviors.
evidence that the intervention reduces HIV risk behaviors, including number of sex partners, 

number of sex partners with whom meth is used and episodes of condomless sex with 
serodiscordant partners. 
 Using data from our prior trial on baseline means, within-subject 
 MDEs: 
correlation, and over-dispersion, we estimate that the study sample of 60 participants will have 
80% power to detect ~46% net reductions in the numbers of sexual partners. In our Project iN 
study, we have observed statistically significant reductions on sexual risk outcomes ranging 
between 85%-89% among the treatment arm, compared to placebo.
 Therefore, given the 
109
results from the prior trial, we believe that the reductions we are powered to detect in this aim 
are reasonable to anticipate.  
, we will examine how PrEP use and viral 
In sensitivity analyses
suppression status of participants and their partners (partner data assessed via self-reported 
egocentric data collection from participants)
  modify treatment effects on sexual risk 
212
behaviors. We will also examine whether there is evidence of effect modification depending on 
whether both the study participant and partner, the participant only, the partner only, or neither 
the participant nor the partner used a biomedical HIV prevention tool (PrEP or ART).212 
Specific Aim 3: To determine the efficacy of ION vs. placebo in increasing PrEP 
adherence among HIV-negative participants and ART adherence among participants living with 
 We will use GEE Poisson 
HIV, as measured by serum drug-levels and viral suppression rates.
models with robust standard errors to assess evidence that the intervention increases PrEP and 
ART adherence. 
Using the assumptions for loss to follow-up from Project iN for Aim 1, we 
 MDEs:  
estimate that the study sample with 60 participants will have 80% power to detect 10-19 
percentage point increases in PrEP/ART adherence, depending on within-subject correlations and 
adherence levels in the reference group.126,220
The sample size of 60 participants is the minimum number required to have sufficient 
power to determine the MDEs of intermittent naltrexone in reducing meth use for the phase 2b 
study. 
11.4  
Eligible age ranges: 
* 
 AGE RANGE: 
PARTICIPANT
(REQUIRED)
0-6 years
7-12 years
13-17 years
18-64 years
65+
11.5  
 Data will be collected from or about the following types of people (check all 
STUDY POPULATIONS:
* 
 
that apply): (REQUIRED)
Inpatients
Outpatients
Family members or caregivers
Providers
People who have a condition but who are not being seen as patients
Healthy volunteers
Students
Staff of UCSF or affiliated institutions
None of the above
11.6  
Check the populations that may be enrolled: 
SPECIAL SUBJECT GROUPS: 
* 
(REQUIRED)
Children / Minors
Adult subjects unable to consent for themselves
Adult subjects unable to consent for themselves (emergency setting)
Subjects with diminished capacity to consent
Subjects unable to read, speak or understand English
Pregnant women
Fetuses
Neonates

Prisoners
Economically or educationally disadvantaged persons
None of the above
11.7  
 Briefly describe the population(s) that will be involved in this study. Include 
INCLUSION CRITERIA: 
anyone that data will be collected from or about (e.g. patients, healthy controls, caregivers, 
providers, administrators, students, parents, family members, etc.):
Inclusion Criteria:  1) cisgender male (male gender and sex assigned at birth); 2) age 18-70 
years* (naltrexone’s tolerability and safety has been demonstrated among older adults up to age 
70
); 3) self-reported condomless anal sex with men or missing PrEP or ART doses due to 
166,167
meth use in the prior three months while under the influence of meth; 4) self-reported meth use 
at least weekly;  5) positive meth sample via sweat patch or urine testing during screening; 6) 
mild, moderate, and severe meth use disorder as determined by DSM-V-SCID criteria; 7) 
interested in reducing meth use;  8) no current acute illness requiring prolonged medical care; 9) 
no chronic illness that is likely to progress clinically during trial; 10) able and willing to provide 
informed consent and adhere to visit schedule; 11) current CD4 count ≥ 200 cells/mm3; or CD4 
count of 100-199 cells/mm3 and HIV viral load < 200 copies/mL (if living with HIV); 12) baseline 
CBC, total protein, albumin, glucose, alkaline phosphatase, creatinine, BUN, and electrolytes 
without clinically significant abnormalities as determined by study clinician in conjunction with 
symptoms, physical exam, and medical history. 
11.8  
 List any exclusion criteria (e.g. reasons why someone would not be included 
EXCLUSION CRITERIA:
in the study):
Exclusion Criteria: 1) any psychiatric (e.g., depression with suicidal ideation) or medical 
condition that would preclude safe participation;  2) known allergy or prior adverse reaction to 
naltrexone; 3) current use of any opioids or a known medical condition which currently requires 
or may likely require opioid analgesics; 4) opioid-positive urine test at screen/enrollment visits 
(naltrexone can induce opioid withdrawal); 5) moderate or severe liver disease (AST, ALT, or total 
bilirubin 
 3 times upper limit of normal); 6) impaired renal function (creatinine clearance < 60 ml
>
/min); 7) currently participating in another intervention research study with potential overlap; 8) 
severe alcohol use disorder as determined by DSM-V SCID criteria; 9) any condition that, in the 
PI and/or study clinician’s judgment interferes with safe participation or adherence to study 
procedures. 
11.9  
Do any study activities take place on any 
* RESEARCH CONDUCTED ON PATIENT CARE WARDS: 
patient care units including inpatient wards, peri- or post-operative care units, operating rooms, or 
 
in the Emergency Department at UCSF Health medical facilities: (REQUIRED)
  Yes  
  No
11.11  
Does your protocol or study involve any of the following patient 
EMERGENCY DEPARTMENT: 
* 
related activities in the emergency department (e.g. subject identification, recruitment, consent, 
blood draws, specimen retrieval, involvement of ED staff (nursing, tech, and/or physician), or any 
other ED based procedures): (REQUIRED)
 
  Yes  
  No
12.0
 Recruitment and Consent
12.1  
Is this a competitive enrollment clinical trial? By competitive 
* COMPETITIVE ENROLLMENT: 
enrollment, we mean that sites who do not enroll participants early may not get to participate at all: 
(REQUIRED)  

  Yes  
  No
12.2  
 
What kinds of methods will be used to identify potential 
* SUBJECT IDENTIFICATION METHODS: 
participants for recruitment (check all that apply): (REQUIRED)
Review of patients' conditions, history, test results, etc. (includes patients seen in clinic, 
scheduled for surgery, a procedure, imaging, or tests, or seen in the Emergency Department 
as well as searching through medical record data for possible cohort identification)
Already approved recruitment registry
Re-contact of participants from the investigators' previous studies
Referrals from colleagues (attach the 'Dear Colleague' letter or other recruitment materials 
you will provide to colleagues)
Referrals from the community / word of mouth
Advertisements (flyers, brochures, radio or t.v. ads, posting on clinical research sites or social 
media, presentation of the study at community events/media, etc.)
Online recruiting tool (describe below)
CTSI Recruitment Services unit
Posting on UCSF Clinical Trials, ClinicalTrials.gov or other publicly available clinical trial website
Other method (describe below)
Attach your recruitment materials (e.g., flyers, ads, recruitment 
letter templates, email text, etc.) in the Other Study Documents 
section of the Initial Review Submission Packet Form.
* Provide details about the subject identification methods: (REQUIRED)
Snowballing sampling: Study participants enrolled in our pharmacologic trials are encouraged 
to refer
other potential participants. We will provide to participants IRB-approved educational materials 
about the
study that they can give to friends and acquaintances; the friend or aquanitance will then have 
the option
of contacting study staff if interested. We willl not accept names or phone numbers from the 
referring
participant. This is a method to reach some people we may miss via our other recruitment 
strategies. We
would like to add a stipend for situations in which a participant refers a person to the study and if 
that new
person completes a screening visit, the participant will receive $10 and if the new person enrolls 
in the
study, the participant will receive $40.
Mobile-based smart-phone apps recruitment: The team expects that many of our 
participants utilize
mobile technologies to connect with other participants. The team plans to recruit participants 
from the
popular mobile-based applications including Facebook, Instagram WhatApp, Grindr, Scruf, Jack’d, 
Barebarckrt,
Instagram and other social networking platforms. In previous studies we have placed ads on 
these sites
and if a person is interested they will send us a private message and we will respond to that 
message. We
do not create profiles and pro-actively reach out to potential participants on these apps.
Internet-based recruitment: ResearchMatch sends the study recruitment message to matched
volunteers to inform them about a new opportunity to participate. Once individuals respond with
permission to be contacted for that study, personal contact information is made available to the 
researcher
within the secure ResearchMatch system. Online advertising will be used to recruit potential 
participants.
Advertisements will be selected based on study eligibility criteria (e.g. age, sex, interest in study-
related
topics). Advertisements will consist of a combination of ad text and images (see attached 
document

“Online Recruitment Ad text and images” and https://buildclinicalmaterials.my.canva.site
) that will be used in combination and may appear as 
/bcfs00523-ucsf-santos-mud-materials
banners,
posts, text, or URLs links for users to click on if they are interested in the study. By clicking on an
advertisement, the user will be directed to our study screener. Until recruitment for the study is 
complete,
we will be assessing the advertisements on a regular basis.
 
 Did all the participants of previous studies provide permission to be 
*
contacted for future studies: (REQUIRED)
 Yes  
 No
12.4  
How, when, and by whom will eligibility for recruitment be 
DETERMINATION OF ELIGIBILITY: 
determined:
Potential participants will be recruited from via advertisements, active recruitment and snowball 
sampling.
Recruited individuals will be asked brief general eligibility questions through a web-based, IRB 
approved
field screeing survey in person or over the phone by research study staff after providing verbal 
consent. Potential participants who have phone-screened eligible wil be scheduled for an in-
person visit where consenting and further eligibility will be assess via clinical examination, 
laboratory safety testing, meth use frequency, prior to randomization.
12.5  
Who initiates contact (check all that apply): 
INITIATION OF CONTACT: 
* 
(REQUIRED)
Investigators/study team
UCSF recruitment unit (e.g. CTSI Consultation Services)
Potential participant
Other (explain below)
Click here to review the process and rules for use of CTSI's 
Consultation Services for recruitment. 
12.6  
 (check all that apply): 
HOW IS CONTACT INITIATED:
* 
(REQUIRED)
In person
Phone
Letter / email
Website or app
Other (explain below)
Attach the telephone recruitment script in the Other Study 
Documents section of the Initial Review Submission Packet Form. If 
potential participants will initiate contact, attach the telephone 
screening script that will be used to provide more information about 
the study and determine if callers are eligible to participate.
Attach the recruitment letter or email template in the Other Study 
Documents section of the Initial Review Submission Packet Form.

Provide the URL for any website in Recruitment Plan section, or 
attach a mock-up of the website or the app screens in the Other 
Study Documents section of the Initial Review Submission Packet 
Form.
12.7  
Based on the checkboxes you chose above, please provide a narrative 
RECRUITMENT PLAN: 
describing your recruitment plan. We want to know:
Who is conducting the search for potential participants, and how?
How are potential subjects being approached for recruitment? By whom, and when?
If there will be more than one participant group (e.g. patients, healthy controls, caregivers, family 
members, providers, etc.), provide details about the recruitment plans for each group. 
(Recommended length - 100-250 words)
Participants, prior to randomization, will be pre-screened by trained outreach staff using IRB-
approved procedures. In a
confidential manner, staff will inform participants of the study, emphasize that participation is 
voluntary,
and provide the individuals with IRB-approved flyers that describe the study.   Interested potential
participants will be scheduled for an office visit to meet individually with study personnel who will 
begin the
informed consent process. For the pilot randomized trial, recruitment will be conducted using 
techniques
complementary to ongoing onsite research studies using several strategies that have proven 
successful in
prior trials for people with meth use. The team will leverage our existing recruitment resources 
from our
ongoing studies to recruit participants with the following approaches:
Advertisements: The team will run biweekly advertisements in the local papers.Mobile-based 
smart-phone apps recruitment: The team expects that many of our participants utilize mobile 
technologies to connect with other people with meth use disorder. The team plans to recruit 
participants from the popular mobile-based applications including Facebook, WhatApp, Grindr, 
Scruf, Jack’d, Barebarckrt, and Instagram.
 
Internet recruitment: As in our current studies, internet-based recruitment will occur through
strategic placement of banner ads on Web sites frequented by people with meth use disorder, 
including Adam-4-Adam,
craigslist.org, facebook, manhunt.net, barebackrt, Fridae.com, and tweaker.org. Additionally, we 
will use
ResearchMatch to send potential matched volunteers the study recruitment message that will 
inform them
about a new opportunity to participate. Once individuals respond with permission to be contacted 
for that
study, personal contact information is made available to the researcher within the secure 
ResearchMatch
system. Online advertising will be used to recruit potential participants. Advertisements will be 
selected
based on study eligibility criteria (e.g. age, sex, interest in study-related topics). Advertisements 
will
consist of a combination of ad text and images (see attached document “Online Recruitment Ad 
text and
images”) that will be used in combination and may appear as banners, posts, text, or URLs links 
for users
to click on if they are interested in the study. By clicking on an advertisement, the user will be 
directed to
our study screener. Until recruitment for the study is complete, we will be assessing the 
advertisements on
a regular basis.
The team will utilize the efforts of existing field recruiters from other ongoing
Active recruitment: 
studies to recruit for participants on the street in neighborhoods and at street fairs and other 
events
frequented by meth using participants, collecting phone numbers of interested potential 
participants, and leaving
cards and fliers in meeting places, local CBOs, bars, and clubs. Potential participants will be given 

IRB
approved recruitment materiales with promotionals. Potential participants who complete the web-
based
field screening survey and provide contact informaton will be entered into a drawing for a gift 
card. A list
of venues that will be canvassed by our field recruitment team is included in the Appendix.
Snowball sampling: Study participants are encouraged to refer their friends by taking cards and
fliers so that potential participants can call us. This is a method to reach some people we may 
miss via our
other recruitment strategies.
 
Health providers and Community based organizations: Health providers and community-based
organizations are encouraged to give IRB approved recruitment materiales to potential 
participants. We will recruit at some SFDPH 
health clinics such as Ward 86 and Bayview clinic to expand our outreach activities.  We can 
provide health provider's with a study presentation and refreshment.
12.8  
How will permission to participate (i.e., informed consent) be obtained from 
CONSENT METHODS: 
* 
each potential participant. If there will be multiple groups and different plans for consenting each, 
  
check all that apply. See the orange Help bubble to the right for more detailed guidance.  
 
Participants will (check all that apply): (REQUIRED)
Sign a paper consent form at the end of the consent discussion (signed consent)
Sign an electronic consent form using DocuSign (signed consent)
Provide online consent through an app, a website, or a survey tool such as Qualtrics or 
REDCap (waiver of signed consent)
Be told about the study and be given a handout/information sheet and be asked if they agree 
to participate (verbal consent - waiver of signed consent)
Complete the study activities and turn in materials, as in the case of a completed survey that 
is placed in a drop box or mailed to the study team (implied consent - waiver of signed 
consent)
Not be able to provide consent and will have a family member consent for them, as in the 
case of a critically ill or unconscious patient (surrogate consent)
Not be able to provide consent (emergency waiver of consent - allowed for minimal risk 
research or greater than minimal risk research with an approved community consultation plan)
Not know about the study, as in the case of chart reviews or observations of public behavior 
(waiver of consent)
Other method (describe below)
Attach your consent form, information sheet, or electronic consent 
text in the Informed Consent Documents section of the Initial 
Review Submission Packet Form.
As of Winter 2020, the UCSF Version of DocuSign is not Part 11 
compliant. Part 11 compliance is required for FDA-regulated studies 
(studies using of investigational drugs or devices or studies of 
approved drugs or devices for investigational use). UCSF is 
currently pursuing a Part 11-compliant version of DocuSign. Please 
check the 
webpage for updated 
UCSF 21 CFR Part 11 Compliance 
information about the availability of Part 11-compliant DocuSign at 
UCSF.
12.9  
Describe the process for obtaining informed consent, including details such as 
CONSENT PROCESS: 
* 
who will have the consent discussion and when participants will be asked to sign the consent form in 
relation to finding out about the study: (REQUIRED)   We encourage researchers to review our 
.
guidance on obtaining and documenting informed consent
If there are multiple groups being consented differently, provide details about the consent 
process for each group.
If you are relying on 
, provide details about how that will happen.
verbal or implied consent

For studies using online recruitment and consent or consent via mail, provide details here.
Recruited individuals will be asked brief general eligibility questions through a web-based, IRB 
approved
field screeing survey in person or over the phone by research study staff after providing verbal 
consent.We are using the documentation for a waiver of signed consent (section  12.13) for 
verbal consent to ask the field screening questions (see other study documents). These questions 
are no more than minimal risk of harm to subjects and involves no procedures for which written 
consent is normally required outside of the research context. 46.117(c).  Potential participants 
who have phone-screened eligible wil be scheduled for an in-person visit where consenting will 
take place.
 
The consent process will discuss the 2:1 random assignment of participants to receive oral 
naltrexone or placebo
and will detail the potential adverse effects of naltrexone. It will also discuss the weekly 
substance use
counseling sessions. The consent process also addresses participant rights, including the 
voluntary nature
of participation and ability to decline without penalty. Mechanisms for maintaining confidentiality 
will also
be discussed, as well as exceptions to confidentiality which is required by law. Participants will be 
given a
copy of the Human Subject's Bill of Rights, along with a copy of the consent form. Participants are 
given
the contact numbers of both the PI and the UCSF IRB to answer questions about the study or one’
s rights
as a human subject. All participants will meet with a study clinician for an additional opportunity 
to ask
questions. Similar to our prior pharmacologic studies, all participants must also correctly complete 
an
“Assessment of Understanding” quiz. The quiz will include 10 to 12 true/false study-related 
questions that
assess participants’ understanding of basic study concepts, including the unknown efficacy of oral 
naltrexone to
reduce meth use, its side effect profile, the randomization process, and the nature of placebos.
After the assessment of understanding has been completed and staff are satisfied that the 
participant is
able to give full informed consent (including, but not limited to, a participant completing the quiz 
with an
80% score or greater and a demonstrated ability to fully understand corrected answers), the 
consent form
will be signed by the participant.  During COVID-19, we may administer the consent form over 
zoom on a remote visit and use an app (Docusign or Redcap) to sign the consent form online to 
reduce the amount of time the participant is at the study site. The staff member obtaining 
consent will also sign both the original and the copy as a witness, completing the informed 
consent process. A copy of the signed form will be given to the client; the original signed consent 
will be kept in a separate, locked file.
 It is important that the people obtaining consent are qualified to do so. 
*
Briefly describe the training and experience these individuals have in 
obtaining informed consent: (REQUIRED)
All staff have undergone the NIH-required training in human subject protections and good clinical 
practice
(GCP) procedures, and are extensively trained on proper procedures for obtaining informed 
consent.
Trained staff will obtain written informed consent prior to enrollment from all study participants 
using IRB approved
informed consent forms. The informed consent process involves a detailed verbal description of
the study; an item-by-item reading of the consent form will be conducted by study staff while the
participant reads along. Trained staff will explicitly cover the purpose, procedures, risks, and 
benefits of
the study.
12.10  
Indicate how the study team will assess and enhance the subjects' 
CONSENT COMPREHENSION: 
* 
understanding of study procedures, risks, and benefits prior to signing the consent form (check all 
that apply): (REQUIRED)   Tip: Review the Consent Comprehension - Learning Notes in the Help 

bubble at the right for specific questions that can be asked to assess comprehension, consider 
using the UCSF Decision-Making Capacity Assesment Tool, and review our guidance on obtaining 
written or verbal informed consent for more detail on how to conduct the assessment.
The study team will engage the potential participant in a dialogue, using open-ended 
questions about the nature of the study or the experimental treatment, the risks and benefits 
of participating, and the voluntary nature of participation
Potential participants will be asked or shown a series of questions to assess their 
understanding of the study purpose, procedures, risks and benefits, as well as the voluntary 
nature of participation (especially appropriate when the consent process happens online or 
through a mobile health app)
Other method (describe below):
Provide details of the other approaches that will be used, if using another 
method to assess comprehension:
At the moment, research staff are in the process of developing the "assessment of 
understanding" for this
study. We plan to submit a modification that will include all of these materials before start-up of 
this study.
12.13  
Select the regulatory category under which 
* WAIVER OF DOCUMENTATION OF SIGNED CONSENT: 
the IRB may waive the requirement to obtain 
consent for this study:
signed 
The only record linking the subject and the research would be the consent document and the 
principal risk would be potential harm resulting from a breach of confidentiality. Each subject 
will be asked whether they want documentation linking them with the research. 46.117(c) 
(1)  
The research presents no more than minimal risk of harm to subjects and involves no 
procedures for which written consent is normally required outside of the research context. 
46.117(c) (2)  
12.14  
What is the estimated time commitment for participants (per visit and in total):
TIME: 
Screening visits will run between 60-90 minutes. Weekly visits will last between 30-45 minutes. 
Enrollment
visits will last about 90-120 minutes. The monthly and post-treatment visits will take 90-120 
minutes.
Total time visiting the study site will be about 930-1305 minutes (15-22 hrs) over a 7-month 
period, with
regular, weekly visits for a 12-week period. 
IMPORTANT TIP: Ensure this information is consistent with the 
information provided in the consent form.
12.15  
Is there a standard of care (SOC) or usual care that would be offered 
ALTERNATIVES: 
to prospective participants at UCSF (or the study site) if they did not participate in this research 
study:
 Yes  
 No
Describe the care that patients would ordinarily receive at the medical 
center if they did not participate in this study (provide details, assuming 
that some of the IRB members are not specialists in this field):
Psycotherapy for meth use disorders would be available. Additionally, participants can ask their 
providers
to prescribe, off-label, the FDA-approved medications for meth use disorder to help reduce with 
their cravings.

12.16  
Is the study drug or treatment available off-study:
OFF-STUDY TREATMENT: 
Yes 
No  
Not applicable 
13.0
 Risks and Benefits
13.1  
Check if your study involves any of these specific research-related risks 
RESEARCH-RELATED RISKS: 
to participants that may need to be disclosed in the consent form:
For interventional studies, risk that the regimen may be more harmful or less effective than 
other available interventions
Risks associated with radiation exposure for imaging studies specifically for research purposes
Risks associated with the administration of contrast agent for imaging studies
Risks associated with withholding of treatment or discontinuation of current treatment (e.g., 
washout period is required by the study protocol)
For randomized, placebo-controlled trials, possible temporary or permanent health 
consequences from the deprivation of effective therapies during the placebo administration 
period
For studies involving a sham surgical procedure, the risk that participants may experience 
increased morbidity without the possibility of benefit
Risks associated with modification or extension of a surgical procedure primarily for research 
purposes (e.g. risks associated with prolonging anesthesia, time in the operating room, etc.)
Risk of pain or physical discomfort caused by the research intervention
Possible personal discomfort due to sensitive topics (stress, embarassment, trauma)
For any boxes checked above, describe how you will minimize these risks 
* 
and discomforts, e.g., adding or increasing the frequency 
of monitoring, additional screening to identify and exclude people with 
diminished kidney or liver function, or modification of procedures such as 
changing imaging studies to avoid giving contrast agent to people who are 
more likely to suffer side effects from it, etc.: (REQUIRED)
This is a double-blind, placebo-controlled clinical trial where participants will be screened for 
diminished kidney or liver functions and if so excluded to participate in the study.  The 
randomized participants will continue to be monitored through safety lab visits at weeks 4, 8 and 
12 to minimize any risk to participant.  AEs will be reported throughout the 12 week study. 
13.2  
Describe any anticipated risks and discomforts not listed above: 
RISKS: 
* 
(REQUIRED)
HIV and STI Testing risks. Participants may experience anxiety surrounding HIV 
t e s t i n g  
r e s u l t s ,
regardless of the outcome. Positive results in particular may be stigmatizing, emotionally 
u p s e t t i n g ,  
a n d
cause psychological distress. Testing will be done by a trained counselor and will include 
e d u c a t i o n  
o n  
t h e
meaning of results, risk-reduction counseling, and referral for treatment. Due to mandated 
r
e
p
o
r
t
i
n
g
requirements, there could be a loss to confidentiality if there is a new case of HIV.
Naltrexone, Opiates and Fentanyl Risk:  Naltrexone is a medication that blocks your 
body’s ability to respond to opiate medicines or drugs, such as Oxycontin, methadone, or heroin. 
If you have taken opiates 7-10 days prior to taking naltrexone, there is a risk of mild to severe 
opiate withdrawal symptoms. If you take opiate medications for pain or are dependent on opiates 
for any reason.  We have included a list of opioid medications in other study documents. If you 
are receiving naltrexone instead of placebo, you may not feel pain relief from opiate medications 
for 24 to 72 hours. This blocking effect can be overcome, but it must be done by an experienced 
physician, usually in the emergency room or hospital. If you take large amounts of opiates, 
including opiate-containing medications such as prescription pain pills (a guide will be given with 

common names of opiate medications) or heroin, this can lead to overdose, including coma or 
death.
On the streets, dealers are mixing fentanyl with other drugs, such as heroin, cocaine, 
methamphetamine, and MDMA. Because fentanyl is cheap and very powerful, adding it to other 
drugs can be more profitable for dealers. This is especially risky when people taking drugs don’t 
realize that fentanyl might be present in their drug supply. Fentanyl is known by such names as 
Actiq
, Duragesic
, and Sublimaze
.  Street names for illegally used fentanyl include 
®
®
®
Apache, Dance Fever, Friend, Goodfellas, Jackpot, Murder 8, and Tango & Cash.
Other potential risks. All participants are informed of the risks involved in blood draws, 
i
n
c
l
u
d
i
n
g
bruising around the needle site, the risk of infection at the needle site, and occasional equipment 
f
a
i
l
u
r
e
 
i
n
the vacuum tubes. Other potential risks to participating in this study include: unauthorized 
d i s c l o s u r e  
o f
confidential information; discomfort or embarrassment related to specimen collection or 
q u e s t i o n n a i r e s
dealing with personal habits and lifestyle, including substance use; and possible unwanted 
e
n
c
o
u
n
t
e
r
s
with friends or associates in the research setting.
13.3  
MINIMIZING RISKS: Describe the steps you have taken to minimize the risks/discomforts to 
subjects. Examples include:
designing the study to make use of procedures involving less risk when appropriate
minimizing study procedures by taking advantage of clinical procedures conducted on the 
study participants
mitigating risks by planning special monitoring or conducting supportive interventions for the 
study
having a plan for evaluation and possible referral of subjects who report suicidal ideation
All potential participants will be evaluated by the study clinician for physical or psychiatric 
illnesses or
other medical criteria that would preclude study participation. Once enrolled, all participants will 
be
provided with a 24-hour pager number by which a study clinician may be contacted to answer 
questions or
to provide direction in case of emergency. Study staff follow an aggressive set of safety 
procedures to
ensure that participants receive a high and consistent level of monitoring that also meets 
reporting
requirements to the IRB. Potential safety issues are reviewed weekly in meetings during which 
staff
discuss potential adverse events for all participants. At any time, persons judged by project 
investigators
to be a danger to self or others, or who are otherwise judged to be in grave danger due to 
medical or
other conditions, will be escorted to the SFGH Psychiatric Emergency Unit. All staff, including 
research
assistants and counselors, receive yearly training for identifying suicide/homicide risk and/or 
dangerous
intoxication, and de-escalation of agitated or angry persons. All staff are trained to appropriately 
respond
to these situations by immediately contacting a study clinician to evaluate the participant.
 
Minimizing the risks of medication side effects. At all times, participants will be encouraged 
to
contact the study clinician if they have questions or concerns about their medication dosage. 
During each
study visit, participants are given the opportunity to discuss any adverse medication effects with 
the study
clinician. Participants will have monthly safety blood tests, including liver function tests, during 
the 12
weeks they are taking study drug. Participants who ultimately do not tolerate their medication 
may be

taken of study medication if needed and will continue to be followed throughout the duration of 
the trial.
 
We will be testing potential participants for opiates, other substances and fentanyl during 
screening since naltrexone can cause opioid withdrawl.  Participants who test positive for opiates 
or fentanyl will not be enrolled in the study.  We will also test participants for opiates, other 
substances and fentanyl during monthly in-office safety visits and any positive results will not be 
given naltrexone.  
 
Minimizing the risks to privacy of individuals or confidentiality of data. The study consent 
form will
inform participants of confidentiality guidelines. Strict confidentiality will be maintained. Records 
that have
personal identifiers (e.g., clinical records) will be stored in a locked cabinet separate from the 
research
record, which will contain only the participant’s ID number. Only the research team and clinical 
staff
assigned to the care of the participants will have access to non-anonymous records. All research 
data are
maintained in binders in locked cabinets. Consent forms, which contain names, are stored 
separately.
Screening and randomization ID numbers are used to identify specific research forms. Files that 
link
participants’ names with screening and randomization ID numbers will be kept in a locked file. No
presentation or publication of the study results will refer to participants individually. Exceptions to
confidentiality for research participants are those required by law and include suspicion of child 
abuse,
elder abuse, and threat of imminent action on suicidal or homicidal ideation. Participants will be 
informed
of these exceptions in the informed consent process. In addition, representatives from NIH and 
the UCSF
IRB will have limited access to the research records (i.e., in the event of an SAE, the IRB may 
request a
review of the chart to assess adequacy of care during the trial). Prior to any sharing of the 
research
dataset, all personal identifiers will be removed. Data will be shared only with researchers who 
have
received IRB-approval for their studies, and who agree not to identify any specific study 
participant in any
way, and who will destroy or return the dataset after completing their analyses.
We follow the Health Insurance Portability and Accountability Act of 1996 (HIPAA) regulations for 
the
protection of private health information for individuals. All study participants screening or 
enrolling in our
studies must sign the HIPAA Authorization Form (unless a waiver of authorization has been 
approved by
the IRB). The Authorization Form is protocol-specific and must be signed along with the consent 
form
when participants first screen or enroll into a study. Before participants sign the Authorization 
Form, study
staff will explain the purpose of the Authorization Form and answer any of the participants’ 
questions.
Participants will receive a signed copy of the Authorization Form. Potential participants who 
choose not to
sign the HIPAA Authorization form will be excluded from study participation.
 
Ensuring medical or professional intervention for adverse events. The study clinician(s) 
will review
data forms daily to monitor safety during the conduct of the trial. If serious or unexpected AEs 
occur
during the trial, the PI will report these occurrences within the specified time frames to the Data 
and
Safety Monitoring Board (DSMB), IRB, NIH, and the FDA as required. All study materials and 
protocols will
be reviewed and approved by the UCSF IRB prior to their use. AE reporting plans are described in 
the Data
and Safety Monitoring plan in this section.

13.4  
Describe the resources in place to conduct this study in a way that assures protection 
RESOURCES: 
of the rights and welfare of participants:   These resources typically include appropriately trained 
and qualified personnel (in terms availability, number, expertise and experience), funding, space, 
  
equipment, and time to devote to study activities.  Depending on the nature of the research study, 
investigators should consider the proximity or availability of critical resources that may be essential 
to the safety and welfare of participants, such as
the proximity of an emergency facility for care of participant injury
availability of psychological support after participation
resources for participant communication, such as language translation services
For the safety to participants and staff during COVID-19, the study has been designed with hybrid 
visits according to Interim UCSF research guidelines.  The weekly visits (weeks 1, 2, 3, 5, 6, 7, 9, 
10 and 11) will be conducted remotely through zoom.  The participant will be given single M-AMP 
urine test kits and urine collection bottles at the in-office visits and trained how to conduct the 
urine test.  The participant is asked to provide a urine sample in the urine collection bottle before 
the video visit.  The participant will dip the M-AMP stick in the urine during the video visit and the 
dip stick will be shown to the counselor.  Due to video resolution, a faint red line may not be able 
to be viewed by video.  If this happens,  the participant will be asked to take a picture of the dip 
stick and upload it to a secure portal or an encrypted e-mail.  After IRB approval, we will test this 
option on RedCAP through the participant survey invitation and embedded image upload 
option.       
13.5  
BENEFITS: 
* 
(REQUIRED) Note: These are the benefits that the IRB will consider during their review. 
They are not necessarily appropriate to include in the consent form.
Possible immediate and/or direct benefits to participants and society at 
large (check all that apply):
Positive health outcome (e.g. improvement of condition, relief of pain, increased mobility, 
etc.)
Closer follow-up than standard care may lead to improved outcomes or patient engagement
Health and lifestyle changes may occur as a result of participation
Knowledge may be gained about their health and health conditions
Feeling of contribution to knowledge in the health or social sciences field
The research presents a reasonable opportunity to further the understanding, prevention, or 
alleviation of a serious problem affecting the health or welfare of children
Other benefit (describe below)
None
Briefly discuss the other possible benefits:
Study participants may reduce their meth use by virtue of study participation. Study medication 
may
help them stop or decrease their meth use; the weekly substance use counseling sessions may 
also help
participants’ recovery from meth use. HIV testing and counseling may help HIV-negative 
participants
decrease their risk of acquiring HIV. HIV-positive participants may also benefit from the 
prevention counseling messages. Possible benefits to society include potentially decreased meth 
use among individuals with a resultant decrease in meth use-related morbidity and mortality.
13.6  
Explain why the risks to subjects are reasonable in relation to anticipated 
RISK TO BENEFIT RATIO: 
benefits, if any, to the participant or society:
There are few anticipated physical, psychological, social, or legal risks. As described above, 
intermittent oral naltrexone is well tolerated. Additional possible risks of participating in these 
studies include: unauthorized disclosure of
confidential information; discomfort or embarrassment related to urine collection or 
questionnaires dealing
with personal habits, lifestyle, drug or alcohol use; possible unwanted encounters with friends or
associates in the treatment setting; and continued drug use. Study procedures are carefully 
crafted and

followed to minimize these risks. If participants were to find any aspects of their involvement in 
the study
physically, psychologically or otherwise uncomfortable, they will be able to discontinue the study
immediately.
The potential social, psychological, and physical risks to participants described above are 
reasonable given
the need to develop new interventions to treat meth users. If naltrexone helps reduce meth use,
results of this study would be of great benefit to meth-using individuals and the community at 
large.
 
Importance of the Knowledge to Be Gained
An efficacious treatment for persons with meth use would radically expand treatment options for
meth use, and have significant public health impact. In addition, among our target population, 
reducing
meth use may have a profound effect in reducing HIV.
14.0
 
Data and Safety Monitoring Plan
14.1  
DATA AND SAFETY MONITORING PLAN (DSMP): 
* 
(REQUIRED) Provide a summary of the DSMP:
All greater than minimal risk studies are required to provide a plan. 
Lack of an adequate plan is one of the most common reasons why 
IRB approval is delayed.
 
Instructions:
Describe the plan for monitoring data quality and participant safety. Key 
areas that should be included in the plan are:
An explanation of the plan to monitor data collection, study progress, 
and safety
A description of who will perform the monitoring and at what 
frequency (e.g., the PI only, a contract research organization, a Data 
and Safety Monitoring Board or Data Monitoring Committee, etc.)
The type of data and events that will be reviewed (e.g., adverse 
events, breaches of confidentiality, unanticipated problems involving 
risk to participants or others, unblinded efficacy data, etc.)
Procedures and timeline for communicating monitoring results to the 
UCSF IRB, the study sponsor, and other appropriate entities
As appropriate:
A plan for conducting and reporting interim analysis
Clearly defined stopping rules
Clearly defined rules for withdrawing participants from study 
interventions
AE Reporting. Each AE will be classified by the study clinician as serious or non-serious, and 
appropriate
reporting procedures will be followed; these decisions will be reviewed on a real-time basis by the 
study
clinicians. An AE is defined as any reaction, side effect, or untoward event that occurs during the 
course of
the clinical trial, whether or not the event is considered medication-related. A new illness, 
symptom, or
worsening of a pre-existing condition or abnormality is considered an AE. Stable chronic 
conditions that
are present prior to clinical trial entry and do not worsen are not considered AEs. For this study, 

AEs will
include symptoms reported by the patient and abnormal measures of clinical importance noted by 
study
staff.
 
Study staff will assess participants for any medical or psychiatric side effects by asking the 
participant
“How have you been feeling since I saw you last?” Study staff will also review the previous AE 
form and
inquire whether any of those events are continuing. Study clinicians will follow all AEs, regardless 
of
severity, until resolution or until four weeks following completion of the trial. Each new or 
unresolved AE
will be recorded on the AE case report form according to standard procedures. All AEs will be 
assigned a
severity (mild, moderate, severe or life-threatening), as defined by the DAIDS Table for Grading 
Severity
of Adult Adverse Experiences for HIV Prevention Trials.148 The study clinician will review the 
information
and offer an educated opinion about the relatedness of the event to the study drug. These data 
will be
reviewed by the PI or Co-Investigator on a weekly basis.
A summary report of all AEs (including SAEs) will be prepared at least every six months 
(frequency
determined by our IRB, DSMB, and NIH), to be submitted to the DSMB, IRB and NIH.
SAEs. SAEs are defined as any fatal event, any immediately life-threatening event, any 
permanent or
substantially disabling event, any event that requires or prolongs inpatient hospitalization, or any
congenital anomaly. This category also includes any other important medical event that a study
investigator judges to be serious because it may jeopardize the subject or require intervention to 
prevent
one of the above reportable outcomes, or which would suggest a significant hazard, 
contraindication, side
effect, or precaution. An unexpected event is one that is not described with respect to nature, 
severity, or
frequency in the current protocol, investigator’s brochure, or product labeling. All AEs that are 
both
serious and unexpected will be reported to the DSMB and UCSF IRB, in writing, within 10 working 
days. If
the SAE is fatal or life threatening, the PI will notify the FDA by telephone within 24 hours, with a 
followup
written report within two working days.
As required, expedited reporting of SAEs to the NIH will adhere to the following guidelines:
1. Apply regardless of the investigator’s assessment of the relatedness of the SAE to the 
intervention
under study;
2. Apply equally to trials requiring an IND and those not requiring an IND;
3. Apply to any SAEs that occur during the post-treatment observation period defined by the 
protocol; and
4. Apply to suicidal or homicidal behavior that causes an SAE in the participant or someone else 
(e.g.,
hospitalization or death).
 
SAE reporting will include a narrative that will provide details of relevant screening measures, 
medical
history and physical findings, treatment compliance, participant reports of SAEs, and any other 
required
information. The completed SAE report will contain: subject’s ID, gender, age, the title and date 
of the
SAE, and narrative explanation. The SAE form will track how the research staff was notified of the 
event,
dates of consent, randomization, study screening for inclusion/exclusion, treatment received, 
outcome of
study treatment, dates and circumstances of the hospitalization/death, whether alcohol or drugs 
were
known to be involved, and participant status at last clinical or research contact. In cases of 
participant
death, the report will also include appropriate substantiation from clinic records, and, whenever 

possible,
copies of the death certificate, autopsy report, or medical record. As Medical Monitor for the 
study, Dr.
Coffin, will state whether the event was expected and assess its relatedness to the study 
medication or
intervention.
Reporting of other study events. As the study is being conducted, Dr. Santos (PI) will inform the 
NIH,
IRB, and DSMB of any changes in recruitment or in the protocol that are relevant to safety, as 
well as any
actions taken by the IRB as a result of its continuing review of the study. In the event of any 
major
changes in the status of an ongoing protocol (which will occur only with IRB approval), the 
contact PI will
inform the NIH’s program officer and the DSMB immediately. Such changes would include, but 
are not
limited to: amendments to the protocol; temporary suspension of patient accrual, or of the 
protocol; any
change in informed consent or IRB approval status; termination of patient accrual or of the 
protocol; or
other problems or issues that could affect the human subjects in the study.
Trial stopping rules: There are no formal trial stopping rules for this study. No formal interim 
efficacy
analysis will be conducted. If it becomes clear that the trial puts undue safety risk on study 
participants,
outcomes are poor, or the trial will not achieve its enrollment goals, consideration will be given to 
stopping
the trial, after consultation with the DSMB, IRB, and NIDA PO. The overall safety risk to study 
participants
will be determined through regular monitoring procedures. Safety issues will be evaluated as they 
arise;
participants are given the pager number of the clinician on call which they can page in the event 
of an
emergency or safety risk. Study clinicians will consult with Dr. Santos, the Principal Investigator 
and Dr.
Coffin, the medical director, on these safety issues on a case-by-case basis as they are reported 
by the
participant. Non-urgent clinical issues that arise during the course of the study are discussed by 
the team’s
research clinicians at the next weekly meeting with the PI Dr. Santos. During weekly meetings, 
study
clinicians will review all the safety issues and incident adverse events (including lab 
abnormalities) for the
study overall, by system category, and by possible relationship to the study drug. The PI will alert 
the
DMSB and the NIDA PO immediately if at any point the team observes an unexpected frequency 
of serious
AEs possibly related to kudzu. At that point, the PI will consult with the DSMB to determine if 
changes to
the protocol or consent form are needed, or if additional safety data are needed to evaluate 
participant
safety. The PI will consult the DSMB to determine if the trial should be stopped after the 
committee has
reviewed available safety data to date.
14.2  
DATA AND SAFETY MONITORING BOARD (DSMB): 
* 
(REQUIRED) Will a Data and Safety Monitoring 
Board (DSMB) be established:
Yes 
No 
14.3  
Provide details about the DSMB, including meeting frequency, and the affiliations 
DSMB DETAILS: 
and qualifications of members:   
If 
Attach the DSMB charter to the Other Study Documents section. 
the DSMB has not yet been established, submit details and the charter to us as soon as they become 
available.

The research team has used the UCLA Data Safety Monitoring Board (DSMB) for Addiction 
Medicine, of
which Dr. Santos is currently a member, for past clinical trials; we will do so for this trial as well. 
The
purpose of the DSMB is to monitor participants’ progress in trials in order to identify emerging and
unexpected events that change the known risks to subjects’ participation. The UCLA DSMB reviews
multiple studies in separate review committees. It has a project director who assigns committee 
reviewers
to review studies. The reviewers remain anonymous to the PI and the coordinator communicates 
the
concerns of the committee to the PI. When the PI responds to the concerns raised by the 
committee, they
also send them through the coordinator who then passes it to the committee. The PIs are never 
part of,
nor sit in the committee that reviews their own study.
The DSMB will be given blinded trial data, but may request unblinding if safety data warrant. The 
DSMB
clinicians will review reported AEs that are identified by study clinicians or other staff members 
who
evaluate the subjects. The statistician will review the data periodically to monitor problems that 
emerge
from AE occurrences as well as subjects’ self-report instruments that query about psychological 
and
physical complaints. The safety monitoring process begins with the initial DSMB review and 
approval of the
protocol. This review is conducted at multiple levels, including not only the DSMB, but also the 
NIH and the
UCSF IRB. For this study,the DSMB will meet six months into the trial or earlier if warranted, and 
then
annually and on an as-needed basis. The DSMB will review the data collected during this trial to 
provide
ongoing information to Mr. Santos, to the IRB, to the NIH, and potentially (if clinically warranted) 
to
subjects about changes in the risks and benefits from research participation. Communication 
between the
DSMB and the study site will be forwarded to the UCSF IRB and the NIH, for consideration as to 
whether
there are changes to risks and benefits, or if any unexpected events have occurred (see DSMBAM 
info sheet in other study documents).
 
Below are members who serve as committee chairs as well as clinical research experts:
• 
 is Professor in both the Department of Family Medicine and the 
Steven Shoptaw, PhD,
Department of Psychiatry and Biobehavioral Sciences at UCLA. Over the past 20 years, Dr. 
Shoptaw has conducted a series of clinical studies in community clinic settings, primarily on topics 
that involve developing medical and behavioral interventions to treat substance abusers.
• 
 is Health Sciences Assistant Clinical Professor at UCLA Department 
Timothy M. Hall, MD, PhD,
of Family Medicine and Center for Behavioral and Addiction Medicine. His research expertise is in 
sexual identity formation, social/sexual MSM networks, non-gay-identified MSM, ethnography and 
MSM substance use.
• 
 is Associate Professor in the Department of Medicine at the University of 
Gayle Baldwin, PhD,
California, Los Angeles. Her research focuses on how specific immune cells fight infectious 
diseases and cancer.
• 
, is an Associate Staff Scientist in the Department of Health Services 
Dominick Frosch, PhD
Research at the Palo Alto Medical Foundation’s Research Institute. He is also an Assistant 
Professor of Medicine at the University of California, Los Angeles. His research is focused on 
developing and implementing interventions to increase patient participation in clinical decision 
making and understanding the effects of health information in the media on behavior.
 
Below are members who serve as experts in biostatistics and epidemiology:
• Scott Comulada, PhD
• Sung-Jae Lee, PhD
• Jesse Fletcher, PhD
• Glenn-Milo Santos, MPH, PhD
 
Below are members who serve as clinical research experts:
• Adam Carrico, PhD
• David Farabee, PhD

• Timothy Fong, MD
• Liz Evans, PhD
• Phillip O. Coffin, MD, MIA
• Lara Ray, PhD
Administrative support staff:
• Uyen Kao, MPH, Director
• Oluwadamilola O. Jolayemi, MSc, Coordinator
15.0
 Confidentiality, Privacy, and Data Security
15.1  
Indicate how subject privacy will be protected:
PROTECTING PRIVACY: 
Conduct conversations about the research in a private room
Ask the subject how they wish to be communicated with – what phone numbers can be 
called, can messages be left, can they receive mail about the study at home, etc.
Take special measures to ensure that data collected about sensitive issues do not get added 
to their medical records or shared with others without the subject’s permission
Other methods (describe below)
15.2  
Do any of the instruments ask about illegal or stigmatized behavior:
SENSITIVE DATA: 
 Yes  
 No
IMPORTANT NOTE: Indicate in the consent form what kinds of 
sensitive information will be collected.
15.3  
Could a breach of 
SIGNIFICANT CONSEQUENCES OF A LOSS OF PRIVACY OR CONFIDENTIALITY: 
privacy or confidentiality result in any significant consequences to participants, such as criminal or 
civil liability, loss of state or federal benefits, or be damaging to the participant's financial standing, 
employability, or reputation:
 Yes  
 No
Check all that apply:
Embarrassment
Criminal or civil liability
Loss of state or federal benefits
Damaging to the participant's financial standing, employability, or reputation
Potential risks to insurability (health, disability, or life insurance)
Describe the potential consequences:
Other potential risks to participating in this study include: unauthorized disclosure of confidential
information; discomfort or embarrassment related to specimen collection or questionnaires 
dealing with
personal habits and lifestyle, including drug or alcohol use; and possible unwanted encounters 
with friends
or associates in the research setting.
15.4  
Explain any extra steps that will be taken to assure 
EXTRA CONFIDENTIALITY MEASURES: 
confidentiality and protect identifiable information from improper use and disclosure, if any:
The study consent form will inform participants of confidentiality guidelines. Strict confidentiality 
will be
maintained. Records that have personal identifiers (e.g., clinical records) will be stored in a locked 

cabinet
separate from the research record, which will contain only the participant’s ID number. Only the 
research
team and clinical staff assigned to the care of the participants will have access to non-anonymous 
records.
All research data are maintained in binders in locked cabinets. Consent forms, which contain 
names, are
stored separately. Enrollment and randomization ID numbers are used to identify specific 
research forms.
Files that link participants’ name with enrollment and randomization ID numbers will be kept in a 
locked
file. No presentation or publication of the study results will refer to participants individually. Prior 
to any
sharing of the research dataset, all personal identifiers will be removed. Data will be shared only 
with
researchers who have received IRB-approval for their studies, and who agree not to identify any 
specific
study participant in any way, and who will destroy or return the dataset after completing their 
analyses.
 
The study will follow HIPAA regulations for the protection of private health information for 
individuals. All
study participants enrolled or enrolling in our studies must sign the HIPAA Authorization Form. The
Authorization Form is protocol-specific and must be signed along with the consent form when 
participants
first screen or enroll into a study. Before participants sign the Authorization Form, study staff will 
explain
the purpose of the Authorization Form and answer any of the participants’ questions. Participants 
will
receive a signed copy of the Authorization Form. Potential participants who choose not to sign the 
HIPAA
Authorization form will be excluded from study participation.
 
For the safety to participants and staff during COVID-19, the study has been designed with hybrid 
visits according to Interim UCSF research guidelines.  The weekly visits (weeks 1, 2, 3, 5, 6, 7, 9, 
10 and 11) will be conducted remotely through zoom.  The participant will be given single M-AMP 
urine test kits and urine collection bottles at the in-office visits and trained how to conduct the 
urine test.  The participant is asked to provide a urine sample in the urine collection bottle before 
the video visit.  The participant will dip the M-AMP stick in the urine during the video visit and the 
dip stick will be shown to the counselor.  Due to video resolution, a faint red line may not be able 
to be viewed by video.  If this happens,  the participant will be asked to take a picture of the dip 
stick and upload it to a secure portal or an encrypted e-mail.  After IRB approval, we will test this 
option on RedCAP through the participant survey invitation and embedded image upload 
option.       
15.5  
Do you anticipate that this study may collect information that State or Federal 
 REPORTABILITY: 
*
law requires to be reported to other officials, such as elder abuse, child abuse, or threat to self or 
others: (REQUIRED)
 Yes  
 No
The confidentiality and privacy section of the consent form should 
include this as a possible risk of participation. 
 
Describe the types of reportable information the research team may 
* 
encounter and provide the details of the reporting plan: (REQUIRED)
Exceptions to confidentiality for participants are those required by law such as a diagnosis of 
sexually transmitted infections (STIs) including HIV, CD4 and Viral Load and threat of imminent 
action on suicidal or homicidal ideation. At any time, persons judged by project investigators to 
be a danger to self or others, will be escorted to San Francisco General Hospital. All staff, 
including research assistants and counselors, receive yearly training for identifying suicide
/homicide risk and/or dangerous intoxication, and de-escalation of agitated or angry persons. All 
staff are trained to appropriately respond to these situations by immediately contacting a study 
clinician to evaluate the participant.

15.6  
Will this study obtain a Certificate of Confidentiality:
CERTIFICATE OF CONFIDENTIALITY: 
 
 Yes  
 No
Please include the recommended Certificate of Confidentiality 
language in the consent form. 
15.7  
Will there be any sharing of 
 research test results 
SHARING OF RESEARCH RESULTS: 
EXPERIMENTAL
with subjects or their care providers:
  Yes  
  No
15.9  
Study data will be: 
* HIPAA APPLICABILITY: 
(REQUIRED)
Derived from a medical record (e.g. APeX, OnCore, etc. Identify source below)
Added to the hospital or clinical medical record
Created or collected as part of health care
Used to make health care decisions
Obtained from the subject, including interviews, questionnaires
Obtained ONLY from a foreign country or countries
Obtained ONLY from records open to the public
Obtained from existing research records
None of the above
Derived from the Integrated Data Repository (IDR) or The Health Record Data Service 
(THREDS) at SFGH
In addition to signing a consent form, each subject will have to sign 
 
the UCSF Research Subject Authorization Form (HIPAA Form). 
Upload the HIPAA Authorization Form in the Other Study 
Documents section of the Initial Review Submission Packet Form. 
Failure to have patients sign the HIPAA Authorization is one of the 
 Please call 
most common findings from QIU Routine Site Visits.
the IRB office at 415-476-1814 if you have questions about HIPAA 
research requirements.  
If derived from a medical record, identify source:
Clarifying health data may be requested from PCP, inpatient and/or ED visits.
15.10  
Check all identifiers that will be collected and included in the research records, 
IDENTIFIERS: 
* 
even temporarily: (REQUIRED)
Names
Dates
Postal addresses (if only requesting/receiving zip codes check Yes to the Zip Code question 
below instead of checking this box)
Phone numbers
Fax numbers
Email addresses
Social Security Numbers*
Medical record numbers
Health plan numbers
Account numbers

License or certificate numbers
Vehicle ID numbers
Device identifiers or serial numbers
Web URLs
IP address numbers
Biometric identifiers
Facial photos or other identifiable images
Any other unique identifier
None
Could study records include 
 photos or images (even 'unidentifiable' 
* 
ANY
ones): (REQUIRED)
  Yes  
  No
* Please provide a justification for including the Social Security Number 
(SSN) in your data set. Best practices dictate that you store the SSN 
separately from the full data set in a password protected file. (REQUIRED)
California regulations require that positive HIV test results be reported to the county public health 
department, even if it is not a new diagnosis for the individual. HIV test result reporting includes 
CD4+ count (or T-cell count), viral load, and viral genotype for positive results. This information 
is used to track the disease statewide and nationwide.
The report includes details like participant name, social security number, and other identifying 
information. The San Francisco Department of Public health may share the results with the 
participant’s home county health department if they do not live in San Francisco County. Other 
than this required reporting, test results will be treated confidentially by the study staff and 
personally identifying information will not be reported to other departments or agencies.
 
 
 
15.12  
 
Will health information or other clinical data be accessed from UCSF Health, 
* PATIENT RECORDS: 
Benioff Children's Hospital Oakland, or Zuckerberg San Francisco General (ZSFG): (REQUIRED)
 Yes  
 No
15.15  
Does the research require access to any of 
HIPAA - PERMISSION TO ACCESS SENSITIVE DATA: 
* 
the following types of health information from the medical record: (check all that apply) 
(REQUIRED)
Drug or alcohol abuse, diagnosis or treatment
HIV/AIDS testing information
Genetic testing information
Mental health diagnosis or treatment
None of the above
Important note: Ensure that participants initial the corresponding 
line(s) in Section C of the HIPAA authorization form during the 
consent process.
15.19  
(check all that apply): 
* DATA COLLECTION AND STORAGE: 
(REQUIRED)
Collection methods:
Electronic case report form systems (eCRFs), such as OnCore or sponsor-provided clinical trial 

management portal
UCSF ITS approved Web-based online survey tools: Qualtrics or RedCap
Other web-based online surveys or computer-assisted interview tool
Mobile applications (mobile or tablet-based)
Text Messaging
Wearable devices
Audio/video recordings
Photographs
Paper-based (surveys, logs, diaries, etc.)
Other:
Specify what other methods will you use to collect data: 
* 
(REQUIRED)
If the counselor is unable to read the urine dip stick through the remote video visit, the 
participant will be asked to take a photo of the dip stick result and upload this to a secure portal 
or encrypted e-mail.
What online survey or computer assisted interview tool will you use: 
* 
(REQUIRED)
Qualtrics (Recommended)
RedCAP (Recommended)
Survey Monkey (NOT recommended and may require UCSF ITS Security review)
Other
What's the name of the survey tool and who is it owned by
* 
: (REQUIRED)
We will use PiLR Health's Ecological Momentary Assessments (EMA)messages for the Ecological 
Momentary Interventions (EMI). To collect self-adherence measures we will use MEMs caps which 
we have used in previous studies.
If the survey tool is not provided by the study sponsor, and the 
, 
survey tool stores data on a server, vendor, cloud, or 3rd party
contact 
 to determine if you need to complete 
datasecurity@ucsf.edu
a security assessment.
Data will be collected/stored in systems owned by (check all that apply): 
* 
(REQUIRED)
Study sponsor
UCSF data center (including OnCore, RedCap, Qualtrics, and MyResearch)
UCSF encrypted server, workstation, or laptop residing outside of UCSF data center
Personal devices, such as laptops or tablets that are not owned or managed by UCSF
SF VAMC
Zuckerberg San Francisco General Hospital
Benioff Children's Hospital Oakland
Langley Porter Psychiatric Institution
Other UCSF affiliate clinic or location (specify below)
Cloud vendor such as Amazon Web Services (AWS), Salesforce, etc. (specify below)
Other academic institution
3rd party vendor (business entity)
Other (explain below)
Provide more details about where study data will be stored: 
* 
(REQUIRED)
All data collected will be collected and stored at the San Francisco Dept of Public Health office on 
25 Van
Ness Ave. Records that have personal identifiers (e.g., clinical records) will be stored in a locked 
cabinet
separate from the research record, which will contain only the participant’s ID number. Only the 

research
team and clinical staff assigned to the care of the participants will have access to non-anonymous 
records.
All research data are maintained in binders in locked cabinets. Consent forms, which contain 
names, are
stored separately.
 
Enrollment and randomization ID numbers are used to identify specific research forms. Files that
link participants’ name with enrollment and randomization ID numbers will be kept in a locked file 
in a
locked room.
 
Information collected through ecological momentary intervention messages will be stored only for 
the duration of the study. No sensitive information is collected. PiLR Health is also a HIPAA 
compliant system.
15.20  
 Will patient records reviewed under this approval be 
* ADDITION OF RECORDS TO A REGISTRY:
added to a research database, repository, or registry (either already existing or established under 
this protocol): (REQUIRED)
  Yes  
  No
15.21  
During the lifecycle of data collection, transmission, and storage, will identifiable 
DATA SHARING: 
* 
 
information be shared with or be accessible to anyone outside of UCSF: (REQUIRED)
  Yes  
  No
16.0
 Financial Considerations
16.1  
Will subjects be paid for participation, reimbursed for time or expenses, or receive any 
* PAYMENT: 
other kind of compensation: (REQUIRED)
 Yes  
 No
16.2  
Subjects payment or compensation method (check all that apply):
PAYMENT METHODS: 
Payments will be (check all that apply):
Cash
Check
Gift card
Debit card
UCSF Research Subject Payment Card
Reimbursement for parking and other expenses
Other:
Specify 
 payment/compensation method:
other
Paypal electronic cash transfers.
16.3  
Describe the schedule and amounts of payments, including the total subjects 
PAYMENT SCHEDULE: 
can receive for completing the study:
If there are multiple visits over time, explain how payments will be prorated for partial 
completion
If deviating from recommendations in Subject Payment Guidelines, include specific 
justification below

Participants will be compensated for their time at each visit and in responding to daily ecological 
momentary messages (up
to a total of $556). Participants will receive $80 for the 2 screening visits ($35 at Screen 1 and 
$45 at Screen 2), $15 for run-in visits 1 and run-in visit 2, $55 for enrollment, $20 for weekly 
visits (1-3, 5-7, and 9- 11), $55 for week 4 (month 1) and week 8 (month 2) visits, and $65 for 
week 12 (month 3). In addition, they will receive $0.40 for each day that they
complete the daily EMA series throughout the 12-week treatment period (up to $36).
 
Participants could receive a gift card ($10) for partial screening visits. Participants could receive a 
gift card ($20) if they confirm and arrive at their scheduled screen 1 in-office visit. Participants 
who are given loaner phones could receive $50 if they return the loaner phone at the week 12 
visit.
For any snowball referral that has completed a screening visit, the participant who referred the 
new participant will receive $10. If the new participant enrolls in the study, the participant who 
referred the new participant will receive $40.
  
16.4  
Will subjects or their insurance be charged for any study activities:
COSTS TO SUBJECTS: 
  Yes  
  No
17.0
 Other Approvals and Registrations
17.1  
 
Does this study involve administration of vaccines 
* ADMINISTRATION OF RECOMBINANT DNA: 
produced using recombinant DNA technologies to human subjects 
: 
(Help Link added Aug '15)
(REQUIRED)
  Yes  
  No
17.2  
Does this study involve human gene therapy: 
* HUMAN GENE THERAPY: 
(REQUIRED)
  Yes  
  No
17.4  
Indicate if this study involves other regulated materials and requires approval 
OTHER APPROVALS: 
and/or authorization from the following regulatory committees:
Institutional Biological Safety Committee (IBC)
Specify BUA #:
Institutional Animal Care and Use Committee (IACUC)
Specify IACUC #:
Controlled Substances
18.0
 Qualifications of Key Study Personnel and Affiliated 
Personnel
 

NEW: January 2019 - Affiliated personnel who do not 
need access to iRIS no longer need to get a UCSF ID. 
Instead, add them below in the Affiliated Personnel 
table below. 
18.1  
 
Qualifications of Key Study Personnel:
Instructions:
 
For UCSF Key Study Personnel (KSP)* listed in 
 select the KSP 
Section 3.0,
from the drop down list and add a description of their study responsibilities, 
qualifications and training. In study responsibilities, identify every individual 
who will be involved in the consent process. Under qualifications, please 
include:
Academic Title
Institutional Affiliation (UCSF, SFGH, VAMC, etc.)
Department
Certifications
NOTE: This information is required and your application will be 
 
considered incomplete without it. If this study involves invasive or 
risky procedures, or procedures requiring special training or 
certification, please identify who will be conducting these 
procedures and provide details about their qualifications and 
training. Click the orange question mark for more information and 
examples. 
 
Training Requirements: 
The IRB requires that all Key Study Personnel complete Human Subjects 
Protection Training through 
 prior to approval of a new study, or a 
CITI
modification in which KSP are being added. More information on the CITI 
training requirement can be found on our 
. 
website  
 
* Definition of Key Study Personnel and CITI Training Requirements (Nov, 
 UCSF Key Study Personnel include the Principal Investigator, other investigators 
2015):
and research personnel who are directly involved in conducting research with study 
participants or who are directly involved in using study participants’ identifiable private 
information during the course of the research. Key Personnel also include faculty mentors
/advisors who provide direct oversight to Postdoctoral Fellows, Residents and Clinical 
Fellows serving as PI on the IRB application.
 
KSP Name
Description of Study 
Responsibilities - Briefly 
describe what will each 
person be doing on the study. 
If there are procedures 
requiring special expertise or 
certification, identify who will 
be carrying these out. Also 
identify who will be obtaining 
informed consent.
Qualifications, Licensure, and 
Training
Dr. Santos is responsible 
for the overall scientific, 
clinical, and operational 
aspects of the study, 
Dr. Santos is a Senior 
Research Scientist in the 

Santos, Glenn-Milo PhD, 
PhD
including: protocol 
development, overseeing 
the study activities and 
the safety of participants, 
data collection and 
management, data 
analysis, and publication 
of study results. Dr. 
Santos holds ultimate 
responsibility for all study 
staff conduct.
Center on Substance Use 
and Health at the San 
Francisco Department of 
Public Health(SFDPH) 
and an Associate 
Professor at the 
Department of 
Community Health 
Systems at University of 
California, San Francisco.
Coffin, Phillip O, MD
Dr. Coffin will assist with 
clinical visits, including 
performing screening, 
enrollment, and follow-up 
visit. He will support 
study
clinical staff in 
determination of 
participant eligibility 
when extensive medical 
expertise is required. He 
will be available on–call 
for study staff and for
participant emergencies 
or questions and will 
meet regularly with staff 
to discuss adverse events 
and other clinical issues. 
Dr. Coffin will assist Mr. 
Santos in study design, 
formulation of the study 
protocol and structured 
interview guide, analysis 
of
the data and integration 
and interpretation of 
quantitative data.
Dr. Coffin is Director in 
the Center on Substance 
Use and Health at the 
San Francisco
Department of Public 
Health. He is a board 
certified infectious 
disease with expertise in 
HIV treatment 
adherence, epidemiology 
of
substance use trends, 
and evaluation of 
pharmacologic 
interventions for 
substance
use.
Dr. Vittinghoff, Eric PhD
Dr. Vittinghoff is 
responsible for the 
statistical integrity of the 
study, including
developing randomization 
procedures, data 
collection instruments, 
ensuring integrity of the 
data collected,and 
developing data analysis 
plans. Dr. Vittinghoff will 
collaborate closely with 
Dr. Santos in study 
design, data analysis, 
and publication of
study results.
Dr. Eric Vittinghoff, PhD 
is Adjunct Professor of 
Epidemiology and 
Biostatistics in the 
Division of Biostatistics at 
the University of 
California,San Francisco.
Dr. Matheson has 
developed the substance 
use counseling sessions, 
trains and supervises
the counseling staff, and 
ensures adherence to the 
protocol. He will meet 
with the counseling staff 
Dr. Matheson, PhD is a 
psychologist in the 

Matheson, Tim
on a weekly basis to 
resolve any counseling 
issues, as well as to 
ensure adherence to the 
counseling protocol. He 
will
also oversee the 
operations related to HIV 
testing and counseling.
Center on Substance Use 
and Health of
the San Francisco 
Department of Health.
Ikeda, Janet
Ms.Ikeda is responsible 
for coordinating the 
study,including 
overseeing the day to 
day activities and 
regulatory reporting, 
quality
assurance checks, lab 
maintenance and 
assisting
with data analysis.
Janet Ikeda is a Research 
Study Coordinator in the 
Center on Substance Use 
and Health at the San 
Francisco Department of 
Public Health.
Walker, John
John Walker is a study 
clinician who conducts 
screening visits and 
determines eligibility of 
potential participants,
performs physical exams, 
medical histories, 
phlebotomy, administers 
study drug,revises 
adverse events and 
manages the laboratory 
and
drug storage.
John Walker,MSN, FNP-C,
is a nurse practitioner in 
the Center on Substance 
Use and Health at the 
San Francisco 
Department of Public 
Health.
Yuhas, Trent W
Mr. Yuhas is responsible 
for conducting study 
visits and assessments, 
including
informed consent, 
performing phlebotomy 
and conducting STI and 
HIV risk reduction
counseling and testing.
Trent Yuhas, M.A., is a 
Research Associate in the 
Center on Substance Use 
and Health of
the San Francisco 
Department of Public 
Health.
Farley, John
Mr. Farley is responsible 
for recruiting potential 
participants for the 
research
study, including field 
screen and the pre-
screening form.
John Farley, BA, is a 
Recruitment coordinator 
in the Center on 
Substance Use and 
Health of the San 
Francisco Department of 
Public Health
Hoffmann, Thomas PhD, 
PhD
Dr. Hoffmann is the bio-
statistician on the study 
and responsible for 
creating the ACASI
questionnaire and 
overseeing the data 
collection and analyses of 
the study.
Thomas Hoffmann, PhD.,
is a Bio-statistician at the 
University of California at 
San Francisco.

Dunham, Alexandrea
Ms Dunham is 
responsible for 
conducting study visits 
and assessments, 
including
informed consent, 
performing phlebotomy 
and conducting STI and 
HIV risk reduction
counseling and testing.
Alexandrea Dunham, BA, 
is a Research Associate 
in the Center on 
Substance Use and 
Health of
the San Francisco 
Department of Public 
Health.
Balcazar, Andrew L
Mr. Balcazar is 
responsible for recruiting 
potential participants for 
the research
study, including field 
screen and the pre-
screening form.
Andrew Balcazar is an 
Assistant Recruitment 
coordinator in the Center 
on Substance Use and 
Health of the San 
Francisco Department of 
Public Health
POPE, EMILY R
Ms. Pope is responsible 
for conducting study 
visits and assessments, 
including
informed consent, 
performing phlebotomy 
and conducting STI and 
HIV risk reduction
counseling and testing.
Emily Pope, BA, is a 
Research Associate in the 
Center on Substance Use 
and Health of
the San Francisco 
Department of Public
Parker, Ella
Ms. Parker is is 
responsible for 
conducting study visits 
and assessments, 
including
informed consent, 
performing phlebotomy 
and conducting STI and 
HIV risk reduction
counseling and testing.
Ella Parker, BA is a 
Research Associate in the 
Center on Substance Use 
and Health at the San
Francisco Department of 
Public Health.
Tavasieff, Sophia R
Ms. Tavasieff is 
responsible for recruiting 
potential participants for 
the research
study, including field 
screen and the pre-
screening form.
Sophia Tavasieff is an 
Recruitment assistant in 
the Center on Substance 
Use and Health of the 
San Francisco 
Department of Public 
Health
Jan, Fareshta
Ms. Jan is responsible for 
conducting study visits 
and assessments, 
including
informed consent, 
performing phlebotomy 
and conducting STI and 
HIV risk reduction
counseling and testing.
Ms Jan, BA, MPH is a 
Research Associate in the 
Center on Substance Use 
and Health of
the San Francisco 
Department of Public 
Health.
18.2  Affiliated Personnel:

Instructions:
 
This section is for personnel who are not listed in Section 3.0: Grant Key 
 because their names were not found in 
Personnel Access to the Study
the User Directory when 
 the iRIS Database and MyAccess directories 
both
were searched. Add any study personnel who fit 
 of the following criteria 
ALL
in the table below:
They meet the definition of Key Study Personnel (see above), and
They are associated with a UCSF-affiliated institution (e.g., VAMC, 
Gladstone, Institute on Aging, Vitalant, NCIRE, SFDPH, or ZSFG), and
They do 
 have a UCSF ID, 
not
and
They do 
 need access to the study application and other study 
not
materials in iRIS.
 in the 
Note: Attach a CITI Certificate for all persons listed below
Other 
 section of the 
Study Documents
Initial Review Submission Packet 
 after completing the 
.
Form
Study Application
 
Click the orange question mark icon to the right for more information on 
who to include and who not to include in this section.
 
Do 
 list personnel from outside sites/non-UCSF-affiliated institutions. 
not
Contacts for those sites (i.e. other institution, community-based site, 
foreign country, or Sovereign Native American nation) should be listed in 
the 
 section of the application.
Outside Sites
 
If there are no personnel on your study that meet the above 
criteria, leave this section blank.
 
Name
Institution
Telephone
E-mail
Role
No External Personnel has been added to this IRB Study
Please describe the study responsibilities and qualifications of each affiliated 
person listed above:
19.0
 End of Study Application
End of Study Application Form
 
:
To continue working on the Study Application
Click on the section you need to edit in the left-hand menu. Remember to save through 
the entire Study Application after making changes.
 
:
If you are done working on the Study Application
Before proceeding, please go back to Section 4.0 Initial Screening 
Important: 
Questions and 
 through the form to make sure all the relevant 
Save and Continue
sections and questions have been included. If you've changed any answers since you 
started, the branching may have changed. Your application will be incomplete and it will 
have to be returned for corrections. 
 
Once you are sure the form is complete, click 
. If this is a new 
Save and Continue
study, you will automatically enter the 
, 
Initial Review Submission Packet Form

where you can attach 
or other 
. Review the 
consent forms 
study documents
Initial 
 for a list of required attachments.
Review Submission Checklist
 
Answer all questions and attach all required documents to speed up your 
approval.
 
 
 
 
 
The UCSF IRB welcomes feedback about the IRB Study Application Form. Please click the link to 
answer a 
 about the application form.
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