Clinical trial NCT03711318
Conditions: Heroin Dependence
Sponsor: New York State Psychiatric Institute
Start date: 2018-11-01; Completion date: 2021-12-31
Enrollment: 8 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A short-term treatment with buprenorphine prior to initiating treatment with naltrexone may increase the proportion of heroin-dependent patients successfully inducted onto Vivitrol.

Detailed description:

Arms: arm 1: Short-term treatment with buprenorphine
Interventions: intervention 1: Buprenorphine/naloxone
Intervention descriptions: intervention 1: 3 week treatment with buprenorphine/naloxone

Protocol documents:
Prot_ICF_000.pdf: 
Protocol Summary Form
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Page 1 of 19
Protocol Title:
Buprenorphine Stabilization and Induction 
onto Vivitrol for Heroin-dependent 
Individuals
Protocol Number:
7699
First Approval:
10/10/2018
Expiration Date:
09/16/2019
Version Date:
10/10/2018
Clinic:
BSU Clinical Service
Contact Principal Investigator:
Adam Bisaga, MD
Email: amb107@columbia.edu
Telephone: 646-774-6155
Research Chief:
Frances Levin, MD
Cover Sheet
Choose ONE option from the following that is applicable to your study
If you are creating a new protocol, select "I am submitting a new protocol." As 5 Year Renewals are no 
longer required, this option remains for historical purposes.
I am submitting a new protocol
Division & Personnel
Division
What Division/Department does the PI belong to?
Substance Use Disorders
Within the division/department, what Center or group are you affiliated with, if any? 
SURC
Unaffiliated Personnel
List investigators, if any, who will be participating in this protocol but are not affiliated with New York 
State Psychiatric Institute or Columbia University. Provide: Full Name, Degrees and Affiliation.
None


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Procedures
To create the protocol summary form, first indicate if this research will include any of the following 
procedures
   Psychiatric Assessment
   Collection of Biological Specimens
   Medication Trial
   Psychotherapy Trial
Population
Indicate which of the following populations will be included in this research
   Medically and Psychiatrically Healthy Subjects
   Adults
   Adults over 50
Research Support/Funding
Will an existing internal account be used to support the project?
No
Is the project externally funded or is external funding planned?
Yes
Select the number of external sources of funding that will be applicable to this study
Funding Source #1
Is the PI of the grant/contract the same as the PI of the IRB protocol? 
Yes
Select one of the following
The grant/contract application is a pending review or a funding decision
Source of Funding
Industry
Sponsor
Alkermes
Is the study investigator initiated? 
Yes
Select one of the following
Single Site
Business Office
RFMH
Does the grant/contract involve a subcontract? 


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No
Study Location
Indicate if the research is/will be conducted at any of the following
   Other Columbia University Medical Center Facilities
This protocol describes research conducted by the PI at other facilities/locations
No
Lay Summary of Proposed Research 
Lay Summary of Proposed Research
Vivitrol is an important option for those desiring detoxification and abstinence from opioids. Initiation of 
Vivitrol in individuals dependent on opioids is challenging, as they must undergo detoxification followed by 
several days of washout before Vivitrol can be administered. Moreover, most patients do not have access to 
an inpatient treatment facility to accomplish this process therefore feasible and effective outpatient 
procedures are necessary to accomplish this transition in many patients. 
 
We have developed an outpatient procedure to accomplish Vivitrol induction on outpatient basis over 5-7 
days but we observed that regular users of heroin have low rates of successful induction. Therefore, new 
strategies are needed for this difficult-to-treat population. We propose to evaluate a new longer  approach 
that involves a three-week period of stabilization on buprenorphine and a slow dose reduction followed by a 
week-long period of opioid withdrawal concurrent with rapid escalation of oral naltrexone doses.
Background, Significance and Rationale
Background, Significance and Rationale
Vivitrol is an important option for those desiring detoxification and abstinence from opioids. Initiation of 
Vivitrol in individuals dependent on opioids is challenging, as they must undergo detoxification first 
followed by several days of washout before Vivitrol can be administered. Moreover, most patients do not 
have access to an inpatient treatment facility to accomplish this process therefore feasible and effective 
outpatient procedures are necessary to accomplish this transition. We have developed an outpatient 
procedure to accomplish this transition in 5 to 7 days which has a success rate of 56%. However regular 
users of heroin have 2.3 lower odds ratio of successful transition than users of prescription opioids. Heroin 
users are now becoming a growing population of individuals seeking treatment and some of them are 
interested in treatment with Vivitrol. Therefore, new strategies are needed for this difficult-to-treat 
population. 
 


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We have been piloting an alternative method of Vivitrol induction for participants who were not successful 
with a 5 to 7 days method. Many of those individuals are regular users of heroin and we have observed that 
the main reason for treatment failure in this population was the ongoing use of heroin during the week of 
oral naltrexone induction. Based on our observation of more than 200 individuals that we treated on 
outpatient basis over the past several years we believe that there are two distinct phenomena that contribute 
to the maintenance of heroin use in these individuals: 1) use of heroin for its euphoric effects (positive 
reinforcement) and 2) use of heroin to avoid withdrawal (negative reinforcement). We hypothesize that 
many heroin users are unable to cope with removal of both sources of reinforcement during an abrupt 
stopping of heroin. Therefore, we propose a treatment approach that would separate those two sources of 
reinforcement, in the first stage treatment will target positive reinforcing effects of heroin and in the second 
stage it will target adverse effects of opioid withdrawal (negative reinforcing effects). The proposed 
approach involves a three-week period of stabilization on buprenorphine followed by a week-long period of 
opioid withdrawal concurrent with rapid escalation of oral naltrexone doses.
Specific Aims and Hypotheses
Specific Aims and Hypotheses
We hypothesize that a short-term treatment with buprenorphine prior to initiating treatment with naltrexone 
will increase the proportion of heroin-dependent patients successfully inducted onto Vivitrol.
Description of Subject Population
Sample #1
Specify subject population
Adults using heroin who meet criteria for opioid use disorder
Number of completers required to accomplish study aims
30
Projected number of subjects who will be enrolled to obtain required number of completers
45
Age range of subject population
18-60
Gender, Racial and Ethnic Breakdown
Both males and females will be recruited. All eligible subjects are accepted; however, past experience with 
recruitment for other studies in this population suggests that the sample will be 75% male, 60% Caucasian, 
30% Hispanic or Latino, and 10% Black or African-American.
Description of subject population
Adult heroin users who currently meet DSM-5 criteria for opioid use disorder.


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Recruitment Procedures
Describe settings where recruitment will occur
All potential participants will be evaluated at the Substance Use and Research Center (SURC)  at the New 
York Psychiatric Institute.    
How and by whom will subjects be approached and/or recruited? 
All patients will be seen by one of our psychiatrists or psychologists for a screening evaluation and mental 
status examination as part of routine admission procedures, Patients who are opioid dependent and appear to 
meet criteria are told about the study and offered further evaluation. Final informed consent for the study 
will be obtained after full psychiatric and medical workup is complete.  Procedures for training staff 
physicians in each protocol and consent form include initial presentations by the Principal Investigator at 
weekly staff meetings, and weekly discussion of inclusion/exclusion criteria and study eligibility for each 
screening participant.   
How will the study be advertised/publicized? 
Once approved by the IRB, advertisements for the study will be placed in local newspapers and radio 
stations. Additionally, prospective participants are recruited by word of mouth through liaison to other local 
clinical services.
Do you have ads/recruitment material requiring review at this time? 
No
Does this study involve a clinical trial?
Yes
YOU MUST REGISTER AT ClinicalTrials.gov IMMEDIATELY UPON RECEIPT OF IRB APPROVAL 
AND PRIOR TO ENROLLMENT OF THE FIRST SUBJECT. YOU WILL BE PROVIDED WITH A NCT 
REGISTRATION NUMBER ON REGISTRATION. PLEASE REVISE THIS SECTION OF THE 
PROTOCOL SUMMARY FORM TO INCLUDE THE NCT NUMBER AND RE-SUBMIT AS AN 
AMENDMENT TO THE IRB.
Concurrent Research Studies
Will subjects in this study participate in or be recruited from other studies? 
No
Inclusion/Exclusion Criteria
Name the subject group/sub sample
Adult heroin users who meet criteria for current opioid use disorder
Create or insert table to describe the inclusion criteria and methods to ascertain them
1. Individuals between the ages of 18-60 (clinical interview)
2. Meets DSM-5 criteria of current opioid use disorder with six consecutive months of reported heroin use, 
supported by a positive urine for opiates indicating regular use of heroin 


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3. Seeking treatment for opioid use disorder with Vivitrol (Clinical interview)
4. Capable of giving informed consent and complying with study procedures  (clinical interview)
5. In otherwise good health based on complete medical history and physical examination, laboratory tests, 
and EKG ( Medical history and physical examination by psychiatrist, laboratory tests (serum Chem-20 and 
CBC, urinalysis) ECG) 
 
6. BMI between 18-40 ( clinical interview, vitals)
Create or insert table to describe the exclusion criteria and methods to ascertain them
1) Reported treatment with methadone in the last 3 months or positive urine toxicology for methadone on 
the day of consent (clinical interview)
2) Maintenance on, or regular use of buprenorphine or other prescription opioids (clinical interview)
3) Pregnancy, lactation, or failure in a sexually active woman to use adequate contraceptive methods. 
(Clinical interview by psychiatrist and medical history by psychiatrist, urine pregnancy test, serum HCG)
4) Active medical illness which might make participation hazardous, such as untreated hypertension, acute 
hepatitis with AST or ALT > 3 times normal, AIDS (CD4 count under 200 currently or medically ill with an 
opportunistic infection), unstable diabetes, cardiovascular disease. (medical history and physical 
examination by psychiatris, laboratory tests: serum Chem-20 and CBC, urinalysis, ECG)
5) Active psychiatric disorder which might interfere with participation or make participation 
hazardous,including DSM-5 Schizophrenia or any psychotic disorder, severe Major Depressive Disorder, or 
suicide risk or 1 or more suicide attempts within the past year. (MINI interview by therapist, clinical 
interview and mental status exam by psychiatrist, contact with collateral information as needed and 
available).
6) Physiologically dependent on alcohol or sedative- hypnotics with impending withdrawal. Other substance 
use diagnoses are not exclusionary. (MINI interview by therapist, Clinical interview by psychiatrist )
7) History of allergic or adverse reaction to buprenorphine, naltrexone, naloxone, clonidine, or clonazepam. 
(Clinical interview by psychiatrist) 
8) Chronic neurocognitive disorder (Clinical interview by psychiatrist)
 
9) History of accidental drug overdose in the last 3 years as defined as an episode of opioid-induced 
unconsciousness or incapacitation, whether or not medical treatment was sought or received. 
(MINI interview by therapist, clinical interview by psychiatrist)
 
10) Painful medical condition that requires ongoing opioid analgesia or anticipated surgery necessitating 
opioid medications (Clinical interviewpsychiatrist)


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11) Fentanyl only use, supported by a urine toxicology that is positive for fentanyl only and negative for all 
other opioids. (Clinical interview, urine toxicology)
 
12) Court mandated to treatment (clinical interview)
Waiver of Consent/Authorization
Indicate if you are requesting any of the following consent waivers
Waiver of consent for use of records that include protected health information (a HIPAA waiver of 
Authorization) 
No
Waiver or alteration of consent
No
Waiver of documentation of consent 
No
Waiver of parental consent 
No
Consent Procedures
Is eligibility screening for this study conducted under a different IRB protocol?
No
Describe procedures used to obtain consent during the screening process 
Potential participants will sign the screening consent page of the study consent form prior to initiating the 
screening process. Following review of screening informed consent, an evaluation team consisting of a 
Masters  level research psychologist and psychiatrist meets with potential participants. The baseline 
evaluation includes a full battery of self-report measures, a structured psychiatric evaluation (MINI 
interview), Hamilton depression scale, a physical examination, and laboratory assessments. Medical 
screening and laboratory work, include vital signs, a physical examination, ECG, serum chemistry, liver 
function tests, complete blood count, and urinalysis obtained by study personnel. Pregnancy tests will be 
conducted for women.
Describe Study Consent Procedures
After the screening evaluation, the study physician will review the study inclusion/exclusion criteria to
determine if the participant is eligible for the study based on the screening materials. If the
participant is eligible for the study, they will be given the consent form to read, and review with the
consenting physician. The study consent will only be signed after all of the participant's questions are
asked, and after all the risks and benefits are explained to and understood by the participant. Study
related procedures will only be initiated after the consent form is signed by both the participant and
consenting physician.
Indicate which of the following are employed as a part of screening or main study consent procedures


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   Consent Form
Persons designated to discuss and document consent
Select the names of persons designated to obtain consent/assent
Bisaga, Adam, MD
Type in the name(s) not found in the above list
Study Procedures
Describe the procedures required for this study
Buprenorphine induction/stabilization/taper: Buprenorphine induction will be conducted at the SURC 
center. After consenting to the study, participants will receive buprenorphine, dispensed weekly, that they 
will take daily. Participants will be stabilized on, and tapered off, buprenorphine over a 3-week period. 
Reductions will occur in a graded fashion, with the stabilization dose reduced to 4mg, according to the 
following schedule: 
Day 0 (Study Consent + ancillary medications). Participants will be advised to abstain from 
opioids for at least 12-16 hours prior to taking their first dose of buprenorphine/naloxone in the 
clinic the next day.
Day 1: After a COWS of 6-10, participants will receive buprenorphine/naloxone 2/0.5mg. If 
tolerated, the patient will receive an additional 4mg onsite, with 2mg to take home that evening. 
Patients will receive a total of 8/2mg on Day 1.
Days 2-7: 8/2 mg buprenorphine/naloxone
Days 8-14: 6/1.5 mg buprenorphine/naloxone
Days 15-21: 4/1 mg buprenorphine/naloxone
 
Participants will attend the center twice weekly and will be assessed for opioid and other substance use 
(urine toxicology and self-report), vital signs, opioid withdrawal symptoms, opioid cravings, and dose 
adjustments of buprenorphine will be made as needed by study physicians. This approach to buprenorphine 
taper is intended to resemble standard clinical practice, in which patients seeking transition off 
buprenorphine undergo a slow taper. The purpose is in part to provide a slow transition with minimal 
withdrawal symptoms. Participants will have at least two study visits a week during the buprenorphine 
taper, but may be seen more regularly at the center if deemed clinically necessary. Participants will be 
required to submit at least one opioid negative urine (except for buprenorphine) during the last two weeks of 
the buprenorphine taper. Participants who are not able to submit at least one opioid negative urine 


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during the last two weeks of the buprenorphine taper will be offered buprenorphine to resume in the 
clinic and will be provided with referrals.
 
Naltrexone induction procedure: Participants who successfully complete the taper must then complete a 
two-day washout (abstinence from opioids, buprenorphine). During this 48-hour period, participants will 
report to the center daily for vital sign monitoring  and to receive standing doses of ancillary medications 
(clonidine, clonazepam, zolpidem, prochlorperazine) to alleviate withdrawal and discomfort with additional 
doses as needed. After abstinence of >/= 48 hours from the last buprenorphine dose, to allow for mu 
receptor availability, participants will begin the naltrexone induction, using a  3 day ascending taper of oral 
naltrexone and once the final oral dose of naltrexone 15 mg is tolerated, participants will receive Vivitrol 
injection.  
 
The administration of naltrexone will occur within a detoxification suite, consisting of a private room 
outfitted with two comfortable reclining lounge chairs, adjustable lighting, and an entertainment system. 
Participants will be monitored by clinical staff frequently, with vital signs checks and withdrawal 
assessments. Transportation home by car service will be provided at the end of the day for any patient 
deemed to have this clinical need. 
 
On Day 1 of the naltrexone induction, participants a pre-treated with prochlorperazine, clonidine, and 
clonazepam, followed by the first dose of naltrexone 1.5mg. If the first dose of naltrexone is tolerated, a 
second dose of 1.5mg will be administered. Ascending split doses of naltrexone will be titrated up slowly, 
until the final total dose of 15mg has been given on Day 3 (Day 1: 1.5-3mg, Day 2 : 3-6mg, Day 3: 15mg).   
Ancillary medications will be offered daily during the induction week and will include clonidine for 
myalgias, prochlorperazine for nausea, clonazepam to reduce anxiety and dysphoria, and trazodone or 
zolpidem for insomnia. Participants will be provided take-home doses of ancillary medications in small 
doses for one week post-administration of Vivitrol.  Once a total of 15mg of naltrexone has been tolerated 
(at least 1.5 hr. observation), the participant may receive 380mg IM Vivitrol. As noted in the section for 
Procedures for Missed Doses of Vivitrol, if relapse is suspected (the participant reports opioid use, and/or 
has a positive UDS for opioids) and there is a risk that the participant has developed physical dependence 
(e.g., delay in receiving scheduled injection or subjective effects suggesting that the block is incomplete) a 
naloxone challenge will be administered before the participant receives their next injection. 
 
For female participants, a urine pregnancy test will be obtained on the day of Vivitrol administration. If at 
any time during the study a female participant has a positive urine pregnancy test, this will be reported to the 
FDA and IRB, the participant will be discontinued from the study, and transitioned to a treatment program 
in the community. 
 
If a participant is unable to receive Vivitrol on induction Day 3, because they were unable to receive 
naltrexone due to opioid intoxication or severe withdrawal, the participant will be given up two additional 
days to attempt the oral naltrexone titration and Vivitrol induction. If a patient fails to succeed with the 
naltrexone initiation procedure, the study team will provide the patient with a weekly supply of 
buprenorphine, and will be provided with a referral.
 
Vivitrol Injections:   Vivitrol will be administered as an intramuscular injection (380mg) in one buttock by 
one of the research psychiatrists or research nurse, who are currently trained and administer Vivitrol in other 


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protocols. Participants will be offered a second injection 4 weeks post administration of the first injection, 
and a 3rd injection 4 weeks later. 
 
Procedures for Missed Doses of Vivitrol: If a patient misses a scheduled second or third injection and takes 
an opioid during at least two of the seven days following the date of the scheduled injection, relapse will be 
suspected(the participant reports recent opioid use, and/or has a positive UDS for opioids) , a naloxone 
challenge may be preformed, if appropriate, using 0.8mg naloxone IM. The patient is followed clinically 
and withdrawal symptoms are assessed over the next hour. If the challenge is negative, the administration of 
Vivitrol will be resumed. However, because there are blood levels and partial blockade beyond four weeks 
after the initial administration of Vivitrol, vulnerability to relapse may be more gradual, and the instance of 
mild or equivocal reactions to the naloxone challenge more common. In this instance, a second challenge 
within 72 hours, will be attempted, and if tolerated, the next injection of Vivitrol can be given. Patients who 
fail two consecutive naloxone challenges are considered to have relapsed and are referred for inpatient 
detoxification or agonist maintenance, as deemed clinically appropriate and in accordance with the patient's 
wishes. Patients who fail two negative naloxone challenges will be given a week supply of 
buprenorphine and will be provided with referrals.
 
Missing a scheduled Vivitrol injection is the most important threat to the success of Vivitrol maintenance. In 
the event of a patient missing a scheduled injection, staff will immediately attempt to contact the patient to 
re-establish commitment to the naltrexone treatment and reschedule the injection within a 24-48 hour 
period. If the patient cannot attend the treatment center within a two-day time-frame, or cannot be located, 
the treatment team will use previously obtained locator information in an effort to locate the patient through 
emergency contacts and try to get them in for a visit.
 
Study Visits
Participants will be seen in the center twice weekly during the buprenorphine stabilization phase and  daily 
on weekdays during the induction phase (Days 1-5) . Once XR-NTX has been administered, participants 
will continue to be seen at the center twice weekly for 12 weeks. At each visit the patient will meet with the 
research assistant to complete research ratings. Research nurse collects safety measures and inquires about 
side effects. Side effects of study medications are reviewed weekly during the visit with a research 
psychiatrist, or more frequently if clinically indicated, and study psychiatrist will adjust medication dose if 
necessary. 
 
At each visit  the patient meets with the research assistant to complete research ratings, including self-report 
of withdrawal, mood, and drug use. The patient provides a urine sample under observation by a staff 
member at each visit. The sample is tested immediately for opiates with the iScreen system (Instant 
Technologies, Inc.). Vital signs are also taken. All data are then brought to the therapist and therapy session 
is held. 
 
Participants may come to the center to be seen as frequently as needed. In particular, any participant who is 
experiencing protracted opioid withdrawal will be offered clinical contact on a frequent, even daily, basis. 
For clinical matters arising in the evenings or on weekends, participants will have access to the 24-hour 
emergency telephone service, staffed by physicians familiar with this protocol who can address patients’ 
concerns.
 


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Behavioral Therapy
Participants will receive counseling focused on medication adherence, education about management of 
withdrawal symptoms, on correct medication usage and the importance of adherence to study procedures 
and abstinence from any substance use outside of the protocol. All participants will receive behavioral 
therapy once weekly during the stabilization and post-induction phase, and  daily (Mon-Fri) during the 
naltexone induction phase. Physician will meet with participants during each visit during the induction 
process and  weekly during the buprenorphine stabilization, and post-induction phases.  The goals of these 
counseling sessions are to: educate and support the patient as he or she stabilizes on XR-NTX, provide a 
motivational platform to discuss pharmacological and nonpharmacological strategies for the management of 
opioid withdrawal symptoms, provide education regarding any medication side effects, and increase 
patient’s motivation to adhere to the XR-naltrexone and to remain on it with the provider in the community 
after the completion of the study.
 
Buprenorphine/naloxone will be offered to participants if they relapse to opioids or if they are unable to 
tolerate study procedures at any point in the study, as well as at the end of study if they no longer wish to 
continue treatment with Vivitrol.
You can upload charts or diagrams if any
Criteria for Early Discontinuation  
Criteria for Early Discontinuation
1) Development of serious psychiatric symptoms as indicated by the Clinical Global Impression (CGI) 
improvement score of 6 (much worse than baseline) or greater for 2 consecutive weeks.
 
2) If the participant's continued opioid use places him/her at risk for self-destructive behavior or other harm 
as indicated by a CGI improvement score of 6 or more (much worse than baseline) for 2 consecutive weeks, 
or as determined by clinical judgement .  
 
3) Development of serious medical condition(s) that may or may not be related to study participation as 
assessed by weekly visits with the psychiatrist, vital sign measurements, and weekly urine toxicology.
 
4) If the participant becomes pregnant as assessed by monthly urine pregnancy testing.
 
Participants may be also removed from the trial if they repeatedly miss scheduled appointments or clinical 
worsening necessitates more intensive treatment (drop out criteria are defined above). Subjects who develop 
serious psychiatric symptomatology (e.g. psychosis, suicidal ideation, severe depressive symptoms) during 
the study period will be dropped from the study and appropriate clinical referrals will be made. This would 
include, but not be limited to, patients who become unconscious after using, engage in destructive or violent 
behavior while intoxicated, report driving while intoxicated, or develop medical complications from their 
opioid use. In all cases where subjects are discontinued from the study, the clinical research staff will 
assume clinical responsibility for the subjects until clinical referrals are operational.
 


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In the case that the patient is removed from the research trial for medical reasons, or is requesting 
withdrawal from the study, he/she will be retained in open treatment for the remaining study period. Upon 
removal of a patient from the trial due to clinical deterioration, the patient will be referred for appropriate 
follow-up treatment, in the most instances either intensive outpatient or residential treatment. The PI or a 
study psychiatrist is available 24 hours/day by phone  and/or beeper in case of emergency.
 
If a patient is discontinued from the study, or decides to withdraw, or relapses during study participation, the 
patient will get treated with buprenorphine until they are linked with a referral for continuing buprenorphine 
treatment. Participants will receive a one-week supply of buprenorphine at a time during the transition 
process. 
 
Buprenorphine will be also offered to participants if they are unable to continue with Vivitrol treatment at 
the end of the study. If additional injections of Vivitrol are available, they will also be offered to patients at 
the end of the treatment study.
Blood and other Biological Samples
Please create or insert a table describing the proposed collection of blood or other biological specimens
Urine samples will be collected at every visit, and we will use onsite testing to provide immediate feedback 
on opiate use to the participant and the treatment team. Blood chemistry will be obtained at baseline and end 
of study. Urine pregnancy tests will be obtained at baseline and prior to each administration of XR-NTX.
Assessment Instruments
Create a table or give a brief description of the instruments that will be used for assessment
MINI- International Neuropsychiatric Interview (MINI) (30 minutes) (Screening Visit)
Psychiatric Interview (30 minutes) (Screening visit)
Medical History (Screening visit)
Physical Exam (Screening and End of Study Visits) 
Urine sample for toxicology (5 min) (Daily during induction phase; bi-weekly during stabilization and post 
induction)
Clinical Global Impression Scale- Observer (CGI-O) (5 min) (Weekly)
Hamilton Depression Scale (HAM-D) (5 min) (Weekly)
Clinical Opiate Withdrawal Scale (COWS) (2 minutes) (Daily during induction phase; bi-weekly during
stabilization and post induction)
Subjective Opioid Withdrawal Scale (SOWS)(2 minutes)(Daily during induction phase; bi-weekly during 
stabilization and post induction)
Systematic Assessment for Treatment Emergent Effects (SAFTEE) (3 min) (Weekly)
Concomitant Medications Form (3 min) (Weekly)
Locator Form (5 minutes) (Baseline)
Craving Scale (2 min) (Daily during induction phase; bi-weekly stabilization and  post induction)


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Vital Signs Nursing Form (3 min) (Daily during induction phase; bi-weekly during stabilization and  post 
induction)
End Study Form (5 min)(End of Study) 
Please attach copies, unless standard instruments are used
Off label and investigational use of drugs/devices
Choose from the following that will be applicable to your study 
Research Related Delay to Treatment
Will research procedures result in a delay to treatment?
Yes
Maximum duration of delay to any treatment 
  A delay of up to 2 weeks is possible prior to enrollment.
Maximum duration of delay to standard care or treatment of known efficacy
Up to two weeks.
Treatment to be provided at the end of the study
All participants who remain active in treatment will have an End-of-Study visit, within a week of the final 
study day (28 days after second XR-NTX injection), during which final ratings measures, and toxicology 
will be obtained. Participants will receive a third injection of XR-NTX at the end of study. At the conclusion 
of the protocol, the participants will be offered supportive therapy for at least one additional month or until 
an appropriate referral for on-going treatment is made. If the patient is
interested to continue on XR-NTX, we will try to work with the patient’s insurance to provide coverage to 
continue XR-NTX. Most insurance plans cover Vivitrol, and we have devloped a network of providers who 
we have referred patients to. If the patient is unable to find a provider to administer injection but we were 
able to secure the medication through patient's insurance and the patient is at risk to become unblocked we 
will administer the injection.
 
Participants who had no response to naltrexone treatment, such as those who continued using opioids while 
on naltrexone as well as those who stopped taking naltrexone (missed scheduled injections) and/or resumed 
opioids after missing naltrexone, are considered to be at very high risk of a full relapse and overdose. 
These individuals will be immediately directed toward either inpatient detoxification followed by a 
residential treatment, or toward agonist maintenance with either buprenorphine/naloxone or methadone. 
Methadone maintenance treatment is widely available in the community; however, access to buprenorphine 
treatment is more restricted.
 
In order to minimize the risk of relapse due to the lack of access to the medication and the gap between
treatment providers we would like to offer 2-week supply buprenorphine/naloxone 8mg to participants who 
are in the process of being referred out to either inpatient treatment or an agonist maintenance program. We 
will continue to provide additional support including frequent, daily if needed visits at our center for a 
maximum of 2 weeks. 


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Clinical Treatment Alternatives
Clinical treatment alternatives
The major alternatives to long-term treatment of opiate dependence is a "drug-free" treatment on either an 
outpatient or residential basis, or agonist maintenance with methadone or buprenorphine, all available by 
referral. Other options available in the community include either hospital-based detoxification (often 
agonist-assisted) to a "drug-free" state, which is available to the patients by referral, or outpatient methadone 
detoxification, which is available at some methadone clinics. Regardless of treatment, the risk of relapse to 
illicit opioid use is very high once the detoxification is completed without medication-based relapse 
prevention treatment. XR-naltrexone is FDA-approved for relapse prevention treatment of opioid use 
disorder. During the initial informed consent process, patients will be informed about alternative treatments 
and their availability, and that they are free to choose among the options, at baseline or at any time during 
the study.
Risks/Discomforts/Inconveniences 
Risks that could be encountered during the study period
Side Effects, Risks, and Interactions of Buprenorphine
Buprenorphine has been associated with adverse effects typical of opioid agonist drugs (e.g. sedation,
constipation, insomnia, headache, nausea), although as a partial agonist such effects are typically less
pronounced than they would be with a full agonist. The most common adverse event associated with the
sublingual administration is oral hypoesthesia. Other adverse events were constipation, headache,
intoxication, disturbance in attention, palpitations, insomnia, sweating, and blurred vision. Buprenorphine 
by itself has little tendency to suppress respiration and is associated with a low risk of overdose, a safety 
advantage. However, there is a risk of overdose if buprenorphine is combined with sedative drugs such as 
benzodiazepines or alcohol, analogous to the risk of combining such sedating medications with a full 
agonist like methadone. As a partial agonist, buprenorphine can precipitate an acute opioid withdrawal 
reaction if taken within 12--18 hours of another short--acting full opioid agonist, or within 48--72 hours of a 
longer--acting full opioid such as methadone. 
 
Discontinuation of buprenorphine is associated with opioid withdrawal symptoms ranging from mild-
moderate to more severe reactions. Study physicians have extensive experience, in both research and
clinical settings, in administering buprenorphine and in the management of opioid withdrawal symptoms. 
The use of buprenorphine is also associated with the risk of using the medication for the purposes of 
intoxication. In the present study we will use buprenorphine/naloxone combination product, which has 
lower abuse liability. If sublingual buprenorphine is used parenterally, there is a risk of precipitated opioid 
withdrawal. Such an event, if it were to occur, would be short-lived and not life threatening. Participants 
will be warned of this risk and advised not to use the medication in this manner. If it is determined that 
patients have been abusing their buprenorphine in such a manner, they will be declared to have failed BUP 
discontinuation, and a new treatment plan will be developed by the patient’s clinical team, with possibilities 
including transfer to buprenorphine or methadone maintenance. To minimize the risk of diversion, 


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medication will be dispensed for short time intervals (1-2 weeks of medication at a time).
Buprenorphine is metabolized principally by CYP3A4. Co-administration of other CYP3A4 inhibitors (e.g. 
anti-- retrovirals efavirenz, delavirdine, atazanavir or atazanavir/ritonavir; the anti-fungal agent
ketoconazole;; antibiotics erythromycin or clarithromycin) may cause an increase in systemic levels of
buprenorphine, although this does not usually have clinically significant effects. When a patient being
prescribed buprenorphine is also receiving other medications, the prescribing physician will check for
potential interactions ahead of time and monitor during treatment.
 
Side Effects of Extended--Release (XR), Injectable Naltrexone
The most common side effect associated with injectable naltrexone is injection site reaction. XR-naltrexone 
is administered as a gluteal intramuscular injection and injection site reactions, mostly pain, and occur in 
approximately 5% of patients in opioid treatment studies. These reactions are generally mild and include 
pain, tenderness, indurations, bruising, pruritus and swelling. Generally these reactions last 1-3 days. Rare 
skin reactions at the site of the injection have been reported, including sterile abscesses, which may relate to 
inadvertent injection into fatty tissue, rather than muscle. Patients will be informed of this risk, and baseline 
physical evaluation will include examination of the buttock for excessive adiposity. If a patient is examined 
by a physician and found to have an abscess, necrosis, cellulitis or extensive swelling, an appropriate 
surgical referral will be made.
Naltrexone has been associated with reversible hepatocellular injury indicated by elevated liver enzymes 
when administered at doses substantially greater than the 380 mg im per month, dose recommended for 
relapse prevention treatment of opiate dependence and proposed for the present study. When used in the 
recommended dose range in opiate--dependent patients, this risk is remote (Brahen et al., 1988; Brewer and 
Wong, 2004). Naltrexone is therefore contraindicated in patients with acute hepatitis or liver failure, and 
such patients are excluded from the study. Patients with hepatic enzyme levels greater than three times the 
upper limit of normal are excluded. Injectable naltrexone achieves higher blood levels than oral naltrexone 
initially, but these should remain lower than levels associated with hepatitis. If naltrexone--induced hepatitis 
were to occur in the setting of long--acting preparation, where the naltrexone would be only very slowly 
eliminated, this would prolong exposure to the offending agent. However, the experience with injectable 
naltrexone also suggests it is safe. In our studies with extended-release naltrexone several patients 
experienced elevation in liver enzymes, which were determined to be related to hepatitis C. In the proposed 
study we will use a long--acting, injectable preparation of naltrexone (Vivitrol 380 mg). Several recent 
reports have documented that naltrexone pose significantly lower risk of hepatotoxicity than previously 
suspected, even among alcohol-- and opioid--dependent persons including those with HCV and/or HIV 
infection (Lucey et al., 2008; Mitchell et al., 2012; Tetrault et al., 2012; Vagenas et al., 2014). These reports 
were used to support decision taken by FDA in July of 2013 to remove the Boxed Warning on the 
hepatotoxicity. Other adverse events seen most frequently in association with XR-naltrexone treatment for 
opioid dependence include nasopharingitis, insomnia and toothache (Vivitrol; Package Insert).
If a patient misses scheduled injection of Vivitrol and resumes regular opiate use, then receiving injectable 
naltrexone will precipitate opiate withdrawal, which may be quite severe in proportion to the time since the 
last injection and the level of opiate dependence. The physician will evaluate the patient and perform a 
naloxone challenge test to determine whether or not naltrexone can be safely resumed. If the naloxone 
challenge is positive (withdrawal is precipitated), then the patient will be removed from the study and 
offered another treatment option such as agonist maintenance (buprenorphine or methadone) according to 
clinical judgment and the patient’s preferences.


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Self-administration of large doses of opiates may over-ride the blockade produced by naltrexone resulting in 
opiate overdosage with its attendant risks including respiratory depression and death. Patients will be 
warned of the severe danger of using opiates, including trying to over-ride the blockade. Also patients who 
have topped naltrexone and resume opiates will not be tolerant initially, so that the quantities of opiates self- 
administered prior to treatment, when they were tolerant, may be quite dangerous in the non-tolerant state. 
Patients will be warned of this. Patients who self-administer opiates to the point of somnolence or stupor 
will be removed from the trial and referred to inpatient detoxification. In the event of a medical emergency 
requiring opiate analgesia, a patient on naltrexone will require higher doses of opiates than normally 
administered. Patients will be informed of this and will be given a naltrexone medication card to carry in 
their wallet.
 
Risks of the Rapid Naltrexone Induction Procedure:
In this procedure withdrawal is then precipitated through administration of oral naltrexone and treated with 
clonidine (an alpha-2 adrenergic receptor agonist which reduces sympathetic nervous system output 
produced by opiate withdrawal), clonazepam (a benzodiazepine which reduces the anxiety and dysphoria 
and permits sleep) and other adjunctive medications. In the proposed protocol the risk of severe withdrawal 
has been minimized by starting naltrexone at the very low dose. Opiate withdrawal causes agitation, 
elevated pulse and blood pressure and other signs of sympathetic arousal, and sometimes confusion. 
Clonidine may produce somnolence or hypotension. Clonazepam commonly may produce somnolence. The 
procedure is contraindicated in patients with unstable medical problems or histories of hypersensitivity to 
any of the medications used, and these are exclusions in the proposed study. The procedure is conducted in 
the outpatient setting that permits monitoring of patients for up to 8 hours daily to permit close monitoring 
of vital signs and mental status.
Pregnancy
Buprenorphine and naltrexone are Pregnancy category C agents, although the safety of buprenorphine in 
pregnancy has been supported in clinical trials (Jones et al., 2010). Female participants will be required to 
use adequate methods of birth control (condom with spermicide, diaphragm with spermicide, birth control 
pills) to be included in the study and will be strongly encouraged to use more effective methods like a 
subdermal implant, IUD, or a depot contraceptive injection. Serum pregnancy tests will be evaluated at 
baseline and urine for pregnancy will be tested as clinically indicated during treatment according to standard 
clinical procedures. If a female patient does become pregnant she will be withdrawn from study medication 
and offered continuing treatment with methadone or buprenorphine, which remains the current treatment of 
choice for pregnant opioid dependent patients.
 
Risks of Relapse
Treatment with buprenorphine is also associated with a high risk of relapse (Raistrick et al. 2005), and a
remote risk of opioid overdose if the patient uses a significant amount of opioids after losing tolerance. Risk 
minimization procedures include exclusion of patients with a history of overdose in the past 3 years , regular 
monitoring of urine toxicology and opioid use, and referral for agonist treatment or inpatient detoxification 
if relapse occurs. 
 
Blood Tests
Blood drawing may cause slight discomfort at site of needle entry, resulting in a small bruise.


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Naloxone Challenge Test
This test will be performed under the supervision of a study physician and will take approximately 45 min to 
complete. The risks of a dose of 0.2-0.8 mg naloxone administered IM are the signs and symptoms 
associated with opioid withdrawal (“gooseflesh,” “vomiting,” “tremor,” “uncontrollable yawning,” etc.). 
These will be assessed every 10 min. for up to 45 min. During the procedure, we will measure blood 
pressure and heart rate before and up to 30 min. after the naloxone dose. 
Describe procedures for minimizing risks
Exclusion Criteria: The exclusion criteria of this study are designed to minimize the risks to
participants. Patients are excluded if they have severe psychiatric illness (mood disorder with
functional impairment or suicide risk, schizophrenia) which might interfere with their ability to participate 
in the outpatient therapy. A history of recent drug overdoses will be exclusionary. Pregnancy, lactation, or 
failure to practice a reliable birth control method is exclusionary, and patients are instructed to inform their 
psychiatrist immediately if they suspect they may be pregnant. Urine HCG is tested during screening and 
monthly throughout the trial. Serum (quantitative) pregnancy test will be obtained during screening. The 
baseline medical evaluation includes physical examination, blood chemistry profile (including liver function 
tests), complete blood count, urinalysis (including HCG), and electrocardiogram, urine toxicology, 
and naloxone challenge if opiate dependence diagnosis is unclear. The evaluating psychiatrist reviews all 
these and takes a medical history.
 
Any disorders which might make buprenorphine-clonidine-naltrexone or naltrexone maintenance hazardous, 
such as uncontrolled hypertension, diabetes, heart disease, hepatitis with transaminase levels greater than 
three times the upper limit of normal, renal disease, or advanced AIDS are exclusionary. Participants with 
uncertain hepatitis status and unexplained liver enzyme elevation > 3 times the upper limit of normal will be 
offered hepatitis panel testing to determine study eligibility. Patients with acute hepatitis infection and 
increasing liver function tests during screening will be excluded from study participation. The patient will 
be assisted in obtaining appropriate medical evaluation and treatment, and may be eligible for the research 
study once the problem is controlled. History of an allergic reaction to any of the medications used is an 
exclusion criterion.
 
Patient Education: All patients will be informed through the informed consent form and discussions with the 
research psychiatrist and therapist of the possible side effects and risks enumerated above. In addition, at 
weekly visits the psychiatrist will query side effects in general, and events of specific concern including 
missing naltrexone doses in conjunction with resumed opiate use or heavy opiate use in an effort to override 
the blockade, and the risk of overdose and death in these situations. Therapists will also be trained to query 
for such events and bring them to the attention of the psychiatrist who will follow up. Patients will give 
informed consent before entering the study. Patients are instructed to call us if any untoward effects occur 
and are given the phone number of our 24-hour answering service. 
 
Patient Monitoring and Removal from Study: The psychiatrist and/or therapist will assess appropriateness 
for continuation in the research study on a continuous basis, and will remove from the trial patients with 
significant clinical deterioration or noncompliance of a type which could be dangerous. If a patient is 
removed from the research trial for medical reasons, he/she will be retained in open treatment for the 
remaining of the study period and will be offered a supply of buprenorphine while transitioning to other 


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treatment. Upon removal of a patient from the trial due to clinical deterioration, the patient will be referred 
for appropriate follow-up treatment, in most instances either inpatient detoxification or residential treatment, 
or methadone maintenance. The PI, Co-PI, or a study psychiatrist is available 24 hours/day by phone and/or 
beeper in case of emergency.
Methods to Protect Confidentiality
Describe methods to protect confidentiality
Patients will be asked to divulge information, such as their drug use or legal, psychiatric or medical 
problems, which are sensitive and could have adverse social consequences if released. This would include 
information released to insurance companies, family members, or made public in any way. Patient records 
are kept in locked files and released only with the patient's signed consent. We will obtain a Federal 
Certificate of Confidentiality to further safeguard the confidentiality of the participants enrolled in the trial. 
The Certificate of Confidentiality will allow investigators and others with access to research records to 
refuse to disclose information that could identify subjects in any civil, criminal, administrative, legislative, 
or other proceeding, whether at the Federal, State, or local level. Contact with family members or significant 
others will only be with the patient's express written consent. All computer data are stored without names or 
other uncoded identification.
Will the study be conducted under a certificate of confidentiality?
Yes, we will apply for the Certificate of Confidentiality
Direct Benefits to Subjects  
Direct Benefits to Subjects
Participants may benefit from many of the components of the treatment that they receive, induction onto
injection naltrexone, naltrexone maintenance, and components of behavioral therapy.
Compensation and/or Reimbursement 
Will compensation or reimbursement for expenses be offered to subjects?
Yes
Please describe and indicate total amount and schedule of payment(s). 
Include justification for compensation amounts and indicate if there are bonus payments.
Participants will receive $40 at each study visit to cover the cost of transportation and time spent completing 
study related forms. Therefore if a patient attends every study visit, they can earn up to $1,720.
References


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References
Anton RF, O’Malley SS, Ciraulo DA, Cisler RA, Couper D, Donovan DM,Gastfriend DR, Hosking JD,
Johnson BA, LoCastro JS, Longabaugh R, Mason BJ, Mattson ME, Miller WR, Pettinati HM, Randall CL,
Swift R, Weiss RD, Williams LD, Zweben A (2006). Combined pharmacotherapies and behavioral
interventions for alcohol dependence: the combine study: a randomized controlled trial. JAMA 295(17):
2003-17.
Brahen, L. S., Capone, T. J., & Capone, D. M. (1988). Naltrexone: lack of effect on hepatic enzymes. The
Journal of Clinical Pharmacology, 28(1), 64-70.
Garbutt JC, Kranzler HR, O’Malley SS, Gastfriend DR, Pettinati HM, Silverman BL, Loewy JW, Ehrich
EW (2005). Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence: a
randomized controlled trial. JAMA 293(12): 1617-25.
Gerra, G., Fantoma, A., & Zaimovic, A. (2006). Naltrexone and buprenorphine combination in the treatment
of opioid dependence. Journal of psychopharmacology, 20(6), 806-814.
Gowing, L., Ali, R., & White, J. M. (2009). Buprenorphine for the management of opioid withdrawal. The
Cochrane Library.
Hammig, R., Kremter, A., Strasser, J., von Bardeleben, U., Gugger, B., Walter, M., Duresteler, K.M.,
Vogel, M. (2016). Use of microdoses for induction of buprenorphine treatment with overlapping full opioid
agonist use: the Bernese method. Subst Abuse Rehabil 20:7:99-105.
Hser, Y. I., Evans, E., Grella, C., Ling, W., & Anglin, D. (2015). Long-term course of opioid addiction.
Harvard review of psychiatry, 23(2), 76-89.
Hulse GK, O'Neil G, Arnold-Reed DE (2004). Methadone maintenance vs. implantable naltrexone
treatment in the pregnant heroin user. Int J Gynaecol Obstet. 85(2): 170-1.
Hulse, G. K., & O'Neill, G. (2001). Methadone and the pregnant user: a matter for careful clinical
consideration. Australian and New Zealand Journal of Obstetrics and Gynaecology, 41(3), 329-332.
Raistrick, D., West, D., Finnegan, O., Thistlethwaite, G., Brearley, R., & Banbery, J. (2005). A comparison
of buprenorphine and lofexidine for community opiate detoxification: results from a randomized controlled
trial. Addiction, 100(12), 1860-1867.
Reece, A. S. (2009). Comparative treatment and mortality correlates and adverse event profile of implant
naltrexone and sublingual buprenorphine. Journal of substance abuse treatment, 37(3), 256-265.
Resnick, R.B., Kestenbaum, R.S., Washton, A., Poole, D. (1977). Naloxone-precipitated withdrawal: a
method for rapid induction onto naltrexone. Clin Pharmacol Ther, 21(4):409-13.
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7699_10.1.18_UNBOLDED.pdf
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7699_10.1.18_BOLDED.pdf
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Buprenorphine Stabilization and Induction onto Vivitrol for Heroin-dependent Individuals 
Principal Investigator: Dr. Adam Bisaga, MD (646)774-6155 
Overview:  Below is a summary of the study that you are being asked to participate in. This outline is 
meant to be a guide for you to use while considering the study and reading the consent form. It is not 
meant to replace the consent form, which you will have to sign if you decide to participate in the study. 
The consent form contains detailed information about the study and about the risks which you will 
discuss it with others before deciding to take part. And remember that, even if you agree to participate, 
you can change your mind at anytime. 
 
Voluntary Participation: This is a voluntary study, and you do not have to participate if you do not want 
to. You may stop participating at any time. You can choose to stop participating at any time.  
Alternatives: Other treatments are available, including methadone maintenance, buprenorphine 
maintenance, inpatient or other outpatient detoxification programs. Maintenance with either 
buprenorphine or methadone is the recommended treatment.  Methadone or buprenorphine 
maintenance are thought to be more effective treatments for heroin or other opioid dependence than 
behavioral therapy and/or outpatient naltrexone treatment. 
Procedures: If you decide to participate in this study, you will initially be assessed for your suitability to 
participate. You will be asked to attend the research center for an initial screening visit, where you will be 
seen by the trial doctor who will check that you are suitable for the study, ask some questions about your 
medical and psychiatric history, general health, treatment history, blood draws, and undergo a physical 
exam. Once you have given your consent to participate in this trial, you will begin your 3-week 
stabilization on buprenorphine/naloxone after abstaining from opioids for 12-16 hours. You will come to 
the clinic twice-weekly complete study assessments, and to meet with your therapist. If you are able to 
abstain from heroin with the help of buprenorphine/naloxone you will be detoxified off it over 5-day 
period when you will receive increasing doses of oral naltrexone and additional medications to help with 
withdrawal symptoms. On Day 5 of the detox week, you will receive an injection of naltrexone (Vivitrol). 
After the detox is completed, you will receive an intramuscular injection naltrexone, a long-acting form of 
naltrexone that lasts in your system for approximately 4 weeks. You will be asked to stay at the clinic for 
at least one hour after receiving this injection, for clinical observation. After receiving the intramuscular 
injection naltrexone, you will continue to receive counseling in the clinic for 12 additional weeks. During 
each visit, you will fill out several questionnaires and answer questions about your alcohol use and other 
drug use. Once each week, you will have a 30-minute session with a therapist and a psychiatrist.   
Risks: There are expected, and potential risks and discomforts associated with participating in this study, 
including: Withdrawal symptoms (nausea, vomiting, diarrhea, muscle and abdominal cramping, 
irritability, anxiety, insomnia) during the first week. If you have stopped taking opioids, or just completed 
detoxification, or you stop taking naltrexone, you may be more sensitive to heroin and other drugs. 
Therefore, amounts of heroin and other drugs that you took routinely in the past may be very dangerous, 
causing overdose; you could die from this. Naltrexone does not block the effects of other drugs (e.g. 
cocaine, tranquilizers, alcohol) and does not reduce the risks in using these substances. Naltrexone can 
cause irritation to the liver, difficulty sleeping, depression, anxiety, nervousness, abdominal pain/cramps, 
nausea and/or vomiting, low energy, joint and muscle pain, headaches, rise in blood sugar levels, 
dizziness, increased breathing, dehydration, sedation, and epileptic seizures. 
Compensation: During the study, you will receive $40 in cash per visit to help pay for your 
transportation costs and for completing study related assessments. You can earn up to $1720 if you attend 
every study visit. 
Benefits: You may benefit directly from the treatment you receive with reduction in your drug use and 
improvement in problems related to your drug use. 
Questions: If you have any questions, contact the research psychiatrist (Dr. Adam Bisaga (646-774-
6155). 


BUP Stabilization 
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1
NEW YORK STATE PSYCHIATRIC INSTITUTE 
 COLUMBIA UNIVERSITY DEPARTMENT OF PSYCHIATRY  
Informed Consent for Participation in Research  
Buprenorphine Stabilization and Induction onto  
Vivitrol for Heroin-dependent Individuals 
 
I. 
Purpose and Overview  
You are being asked to take part in a research study evaluating a new approach to treating opioid 
use disorder. As part of this outpatient treatment you will first be treated with 
buprenorphine/naloxone (Suboxone), a medication for opioid use disorder, for 3-weeks. If you 
are able to remain abstinent form heroin during that period, you will be detoxified off opioids 
over the 5-day period using increasing doses of oral naltrexone and additional medications to 
help with withdrawal symptoms. At the conclusion of this procedure you will receive an 
injection of naltrexone (Vivitrol) to prevent relapse. You will receive two additional injections of 
naltrexone every four weeks for the total of three injections and you will also be receiving 
individual therapy during the 12-weeks of the study. 
Vivitrol is a long-acting injection that contains enough medicine to last for one month blocking 
the effects of opiates and craving. It has no opiate-like effects and is not a controlled substance. 
Vivitrol has been approved by the Food and Drug Administration (FDA) for the relapse 
prevention to opioid dependence following detoxification. You are being asked to participate in 
this study because you are currently dependent upon opiates and meet other study entry criteria. 
The purpose of this research is to develop new procedure for initiating treatment with naltrexone. 
This study is funded by Alkermes, a company that manufactures Vivitrol.  
 
II. 
Voluntary  
Participation in this research study is voluntary. If you decide not to participate, or if you later decide to 
stop participating, you will not lose any benefits to which you are otherwise entitled. A decision not to 
participate or withdraw your participation will not affect your current or future treatment at the New 
York State Psychiatric Institute or Columbia University Medical Center. You will be notified of 
significant new findings that may relate to your willingness to continue to participate.  
 
III. 
Alternative Treatments/Alternatives to Participation  
You do not need to participate in this research study to receive treatment for your opioid use disorder or 
to receive treatment with Vivitrol or buprenorphine. Other treatments are available, including methadone 
maintenance, buprenorphine maintenance, inpatient or other outpatient detoxification programs. 
Maintenance with either buprenorphine or methadone is the recommended treatment.  
 
IV. 
Procedures  
Screening 
The study begins with a screening visit. The medical examinations and laboratory tests for 
screening may be done on one day or over multiple days. You and the study doctor will arrange 


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those times. If you agree to be in this study, you will sign this form before any study procedures 
are done. 
In order to participate in the study, you must first have a psychiatric and medical screening, 
which will include questions about your drug use, health, and other problems you may be having. 
Depending on the results of that, you may also have a cardiogram (a test to measure the electrical 
activity of your heart), blood tests, a physical exam, and a urine toxicology screen. After the 
initial screening visit(s), you will be told whether you may be eligible for this research treatment 
study. The screening process may take between a few days to a few weeks depending on the 
frequency of your visits. If you are not eligible, or if you are not interested in taking part in the 
research treatment, then the clinician will assist you in finding treatment for your problems 
elsewhere. 
Buprenorphine/naloxone Stabilization and Taper 
You will receive a weekly supply of buprenorphine/naloxone that you will take daily according 
to the following schedule: a stable dose of 8/2 mg (Days 1-7), 6/1.5mg (Days 8-14), and 4/1 mg 
(Days 15-21). During this time, we ask that you come to the clinic twice per week so that the 
staff can assess for withdrawal symptoms and make dose adjustments of the buprenorphine 
/naloxone if needed. The purpose of the stabilization and taper is in part to provide a slow 
transition with minimal withdrawal symptoms. 
Detox 
You will have a 2-day washout period following your last dose of buprenorphine/naloxone. We 
will ask you to come to the clinic for both days during this period, so that staff can check you for 
withdrawal symptoms, administer medications to minimize withdrawal, and evaluate readiness 
for oral naltrexone. You will be asked to abstain from opioid use for two days between your last 
dose of buprenorphine/naloxone and your first day of oral naltrexone-assisted detox, and to 
continue to do so for the rest of this week. If you do use heroin or other opiate drugs during this 
period, you may receive a naloxone challenge to determine whether it is safe to continue with the 
rest of the detox schedule. After the 2-day washout period, you will receive the first dose of oral 
naltrexone, and will receive increasing doses up to 15 mg over three days, followed by an 
intramuscular injection naltrexone. At each outpatient visit during the detox, you will need to 
provide an observed urine sample, which will be tested for opiates as well as other drugs. You 
will have your vital signs checked by the staff. In addition, you will receive medications to 
reduce the discomfort of withdrawal from opioids. These include: clonidine (a medicine used to 
treat high blood pressure), clonazepam (for anxiety), prochlorperazine (anti-nausea drug), and 
zolpidem or trazodone (for insomnia). If you experience significant withdrawal while at the 
clinic, you will be strongly encouraged to remain at the clinic for observation, and your 
medication dosage and the length of the detox may be modified. If your withdrawal symptoms 
are more severe, your detox can be extended for 1-2 day, to allow for more time to tolerate oral 
naltrexone. 
You will be free to leave the clinic each day once you have received all necessary medication 
doses and have been evaluated for medical stability by the psychiatrist. If you experience fatigue 
or medication side effects, car transportation home will be provided to you.  
 


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Outpatient Treatment 
After the detox is completed, you will receive an intramuscular injection naltrexone, a long-
acting form of naltrexone that lasts in your system for approximately 4 weeks. You will be asked 
to stay at the clinic for at least one hour after receiving this injection, for clinical observation. 
After receiving the intramuscular injection naltrexone, you will continue to receive counseling in 
the clinic for 12 additional weeks. During each visit, you will fill out several questionnaires and 
answer questions about your alcohol other drug use. Once each week, you will have a 30-minute 
session with a therapist and a psychiatrist.  These sessions will help you work on your treatment 
goals. You will also have your vital signs monitored at every visit. You will be offered two 
additional injections at Weeks 4 and 8 after the first injection.  
You may be given a naloxone challenge test if we have concerns that you are still dependent on 
opioids or if you have relapsed, prior to administering Vivitrol. In order to determine whether or 
not you are dependent on opioids, we may administer up to 0.8 mg naloxone intramuscularly 
(injection in your upper arm muscle), which – if you have recently used opiates - may produce a 
number of withdrawal symptoms, such as nausea, sweating, diarrhea, and anxiety. These 
symptoms will usually wear off between 20-30 minutes. If the symptoms persist, we will offer 
you medications such as clonidine and clonazepam, to help alleviate the symptoms. 
If, during the course of treatment, you relapse to heroin or other opioid dependence and are 
unable to give an opioid-free urine and/or restart naltrexone, you will be provided with referrals 
to alternative treatment programs. We will offer you buprenorphine/naloxone if you relapse to 
opioids or if you are unable to tolerate study procedures at any point in the study. If you use 
heroin during the study but are able to receive your next injection as determined by the naloxone 
challenge, you will continue in the program.  
The most serious risk of study participation is that you will lose tolerance to opiates (the 
effect of heroin, fentanyl, or another opiate on the body is much stronger), and this means 
that resuming use of opiates after detoxifying could cause you to stop breathing and die. If 
you complete the detox and receive intramuscular injection naltrexone monthly, it will help 
to protect you against death due to opioid overdose, because it blocks the effects of opioid 
drugs. But if you stop taking naltrexone injections, restarting opiates could result in 
accidental overdose or death.  
 
End of Study 
At 12 weeks after your first intramuscular injection naltrexone, you will be asked to meet for an 
hour with the psychologist to answer questions about how you have been doing, have another 
physical examination and blood tests, complete some questionnaires, and you will be referred for 
further treatment as part of an after-care plan outside the clinic. You will work with your 
therapist after you receive your last injection of Vivitrol in study week 8 to develop a follow-up 
care plan to continue your treatment. After the study is completed, if you have trouble 
transitioning to your follow-up care provider, you can meet with your therapist weekly for up to 
a month until you have transitioned into the follow-up treatment. 
If you remain abstinent throughout the study, we strongly encourage you to continue treatment 
after study completion and will work with you to help find another treatment provider. If you 
find difficult to remain abstinent (e.g., have strong cravings or use opioids) we will offer you a 


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two-week supply of buprenorphine/naloxone. We will also provide you with referrals for 
Vivitrol, buprenorphine, methadone, and behavioral treatment options. In the event that you 
decide to discontinue from the study, or are withdrawn from the study, you will be treated with 
buprenorphine/naloxone until you have been transitioned to another buprenorphine treatment 
program or provider.  
The doctors conducting this research study are also responsible for your clinical care. If during 
the course of the study, you have a medical emergency or require urgent medical care, the 
research medical staff will consult with your treating physician(s) regarding any information 
relevant to your medical care. In the event of an emergency or if you have questions while in the 
study, you can reach the clinic at (646) 774-6174 during regular business hours or (914) 419-
8921 in the evenings or on weekends.  
 
V. 
Risks and Inconveniences  
The most serious risk of study participation is that you will lose tolerance to opiates (the 
effect of heroin or another opiate on the body is much stronger), and this means that 
resuming use of opiates after detoxifying could cause you to stop breathing and die. If you 
complete the detox and receive intramuscular injection naltrexone monthly, it will help to 
protect you against death due to opioid overdose, because it blocks the effects of opioid 
drugs. But if you stop taking naltrexone injections, restarting opiates could result in 
accidental overdose or death.  
Opioid detox carries a moderately high risk of relapse and a risk of opioid overdose if you use a 
large amount of opioids or if you use opioids that contain fentanyl after losing tolerance. We will 
seek to minimize these risks by monitoring you closely with urine drug tests and asking about 
any opioid use. If you do relapse, you will be given referrals for methadone or buprenorphine 
maintenance or inpatient detox and follow-up treatment.  
 
Buprenorphine/naloxone 
During the buprenorphine/naloxone induction and taper you may experience withdrawal 
symptoms such as difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, nausea 
and/or vomiting, low energy, joint muscle pain, headaches, or runny nose. We do not expect that 
your will require additional medications, as withdrawal symptoms are usually mild during a 
buprenorphine/naloxone taper. However, you will be evaluated by medical staff during each 
daily detox visit, and if you develop significant withdrawal symptoms, these will be addressed. 
Possible medications that may be given include clonidine, clonazepam, trazodone, and zolpidem. 
You may experience discomfort despite their use.  
You may also experience a rapid and sudden onset of withdrawal symptoms if you crush your 
take-home buprenorphine/naloxone pills and either inject or snort them. These symptoms would 
be very uncomfortable but short-lived and not life-threatening, and your psychiatrist would 
evaluate you for them, as well as provide you with referrals to alternative treatment.  
Clinic staff will be monitoring you carefully to make sure you are receiving the optimal dose of 
buprenorphine/naloxone during each day of the induction, stabilization and taper. If you decide 
to take more buprenorphine/naloxone than prescribed during the first week of the study, or 
decide to inject buprenorphine/naloxone, the combination with the additional medications we 


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may be giving you to help with withdrawal symptoms, such as clonazepam, could put you at risk 
of death.  
Opioid medications, like buprenorphine/naloxone, can interact with medicines, such as antidepressants 
and migraine medicines, meant to increase the effects of serotonin, a chemical in the brain. This 
interaction causes a serious response in the brain called serotonin syndrome. If you are taking an opioid 
along with a medicine that increases serotonin and develop symptoms such as agitation, hallucinations, 
rapid heart rate, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble 
with coordination, and/or nausea, vomiting, or diarrhea, you should seek medical attention immediately. 
These symptoms generally start within several hours to a few days of taking an opioid with a medicine 
that increases the effects of serotonin in the brain, but symptoms may occur later, especially after either 
medication is increased in dose.  
Taking opioids may lead to a rare, but serious condition where not enough of the hormone called cortisol 
is produced, particularly during stressful conditions when cortisol is usually produced. Consult your 
study doctor or seek medical attention (ensure that you communicate that you are participating in a 
clinical trial) if you experience symptoms such as nausea, vomiting, loss of appetite, fatigue, weakness, 
dizziness, or low blood pressure. Long-term use of opioid pain medications may lead to decreased sex 
hormones. Inform your study doctor if you experience signs or symptoms of low libido, impotence, 
erectile dysfunction, lack of menstruation, or infertility. 
Naloxone Challenge Test 
Prior to receiving the intramuscular injection naltrexone, you may be given a naloxone challenge 
test if we have concerns that you are still dependent on opioids. In order to determine whether or 
not you are dependent on opioids, we may administer up to 0.8 mg naloxone intramuscularly (by 
injection), which – if you have recently used opiates - may produce a number of withdrawal 
symptoms. You may experience certain effects such as: sweating, restlessness, stomach pain, 
diarrhea, headache, anxiety, nausea, vomiting dizziness, runny nose, yawning, muscle aches, or 
tremors. We will monitor your reactions to naloxone for up to 45 minutes.  
Naltrexone 
Naltrexone will be administered two days after your last dose of buprenorphine/naloxone which 
may precipitates withdrawal. The withdrawal symptoms are then treated with clonidine, 
clonazepam, trazodone, prochlorperazine and zolpidem, but despite their use, you may 
experience significant discomfort. The side effects of these medications may include insomnia or 
possible sleepiness, lowered blood pressure which may produce dizziness or a tendency to feel 
faint, nausea, vomiting, diarrhea, muscle and abdominal cramping, irritability, anxiety, and an 
allergic reaction involving a narrowing of the airways in the lungs, similar to what people with 
asthma sometimes develop.  
Once you are stabilized on naltrexone, this medicine generally has few side effects. It can cause 
irritation to the liver or may occasionally cause or contribute to depressive symptoms. Additional 
side effects may include difficulty sleeping, anxiety, nervousness, abdominal pain/cramps, 
nausea and/or vomiting, low energy, joint muscle pain, or headaches. It is important to note that 
these symptoms may represent persisting withdrawal symptoms, and the psychiatrist who is 
monitoring you can prescribe medications to reduce the discomfort.  
It is very important that you receive the intramuscular injection naltrexone. If you take small 
amounts of heroin or other opiates while on naltrexone, you should feel no opiate-like effects. 
However, it is possible to overpower naltrexone if you take large amounts of heroin or other 


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opiates such as fentanyl, and such an action can be fatal. Also, if you stop taking naltrexone, it is 
possible that you may be much more sensitive to opiates. This means that amounts of heroin or 
other opioids that you used to take routinely could cause you to overdose, stop breathing and die. 
Naltrexone does not block the effects of other drugs such as cocaine, tranquilizers, or alcohol, 
and it does not reduce the risks in using these substances, such as getting drunk, or getting high 
on cocaine or tranquilizer pills. 
 
Vivitrol 
Risks of Vivitrol are possible irritation (e.g., redness, swelling, possible scarring) or infection at the 
injection site. Injection site reactions have ranged from a small, painless area of hardness to pain, 
itching, redness, and swelling. These reactions have typically resolved spontaneously over a period of 1-
3 weeks. Of the 1,000 naltrexone injections we have administered, three to date caused site swelling and 
an open sore to develop, which became infected and required a minor surgical procedure, antibiotic 
treatment and wound care. The wound healed completely over a period of approximately 3 months but 
resulted in a scar.  
Another study risk is that naltrexone may impair the functioning of your liver. Short-term increase of 
liver enzymes can occur, but this is usually reversible. This effect on your liver will resolve after 
naltrexone leaves your body. In addition, administration of naltrexone may increase blood sugar levels, 
which may produce symptoms such as dizziness, increased breathing, dehydration, and seizures. If you 
experience any of these symptoms, it is important that you tell the investigator immediately.  
In rare cases, patients who received injectable naltrexone reported developing a form of allergic 
pneumonia, experiencing shortness of breath. If you have trouble breathing, it is important that you let 
us know right away. In patients treated with the naltrexone injection, we have also observed hives, an 
allergic reaction of the skin with redness and itching. If you develop any of these symptoms it is 
important to let us know.  
If you miss your visit to receive Vivitrol, and/or take opioids, you should come to the clinic 
immediately. There, you will be evaluated to determine if it is safe to restart the naltrexone. You may be 
asked to take an intramuscular injection of naloxone. If your body has become dependent on opioids, 
this dose will produce withdrawal symptoms lasting less than one hour. You may refuse the naloxone 
challenge but must be able to provide an opioid-negative urine or reconsider the challenge within 72 
hours in order to determine whether you can safely restart naltrexone. If at this point, you are found to 
be dependent on opioids and unable to restart naltrexone, you will be provided with referrals to 
alternative treatment programs.  
It is very important that you tell your study physician about any other medications you are taking (either 
prescription or non-prescription) before beginning naltrexone. It is also very important that, during the 
course of the study, you tell your research psychiatrist about any other medications you are prescribed or 
plan to take to avoid possible adverse reactions.  
Comfort Medications 
You will be given comfort medications to help manage your withdrawal during the detoxification. When 
you are taking the comfort medications (clonidine, clonazepam, prochlorperazine, and zolpidem), you 
should use caution when driving a vehicle or operating appliances or machinery. These medications may 
cause some side effects such as sleepiness, lowered blood pressure (which may produce dizziness or a 
tendency to feel faint), or upset stomach.  


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Other Risks 
(For females) Both the detoxification procedure and outpatient naltrexone treatment may pose risk to a 
fetus. You will have a pregnancy test before beginning treatment and monthly thereafter to determine 
that you are not pregnant. You will be asked to use adequate birth control throughout your treatment 
such as: (a) hormonal contraception such as Depo-Provera, daily oral contraceptive, transdermal patch 
or Nuva ring, (b) intra-uterine devices, (c) sterilization, or (d) double barrier contraception, which is a 
combination of any two of the following methods: condoms, spermicide, diaphragm. 
The only risk to the blood-drawing procedures used in this study is the possibility that slight discomfort 
and/or a small bruise or, rarely, a local infection may develop at the site of the needle puncture. This 
seldom occurs. If taking any medication orally, it is being dispensed to you in packages that are not 
childproof. Extra precautions need to be taken to keep the oral medication away from children.  
You will be carefully monitored throughout your participation to minimize the chance of any serious 
adverse side effects. We will provide you with any significant new findings that may develop during the 
course of the study, which may relate to your willingness to continue study participation. If you suspect 
that you might be pregnant, you must inform the study team immediately.  
VI. 
Benefits  
You may benefit directly from the treatment you receive with reduction in drug use and improvement in 
problems related to your drug use. The findings of the study may help doctors know more about how to 
treat opioid dependence and help others with this problem.  
 
VII. 
Confidentiality  
We will do everything we can to keep others from learning about your participation in the research. To 
further help us protect your privacy, the investigators will obtain a Confidentiality Certificate from the 
Department of Health and Human Services (DHHS). With this Certificate, the investigators cannot be 
forced (for example, by court subpoena) to disclose information that may identify you in any federal, 
state, or local civil, criminal, administrative, legislative, or other proceedings. Disclosure will be 
necessary, however, upon request of DHHS for the purpose of audit or evaluation. A Certificate of 
Confidentiality does not prevent you or a member of your family from voluntarily releasing information 
about yourself or your involvement in this research. Note however, that if an insurer, employer or other 
outside party, learns of your participation, and obtains your consent to receive research information, then 
the investigator may not use the Certificate of Confidentiality to withhold this information. This means 
that you and your family must also actively protect your own privacy. Finally, the Certificate does not 
prevent the researchers from reporting suspected or known neglect or sexual or physical abuse of a child 
or threatened violence to self or others. Such information will be reported to the appropriate authorities.  
Records will be available to research staff, and to Federal, State and Institutional regulatory personnel 
(who may review records as part of routine audits). Your name and other personal identifying 
information will be stored in an electronically secure database at New York Psychiatric Institute. Signed 
consent forms and other forms containing identifying information will be kept in a locked file, and all 
interviews, assessments, etc. will be coded with initials and numbers. Electronic data are also coded and 
are stored on computers that are password protected. A description of this clinical trial will be available 
on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information 
that can identify you. At most, the Web site will include a summary of the results. You can search this 
Web site at any time.  
 


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VIII. Study Compensation  
During the study, you will receive $40 in cash per visit to help pay for your transportation costs and for 
completing study related assessments. Below is a breakdown of all the study visits: 
• Screening: 1 visit = $40 
• Consent: 1 visit= $40 
• Buprenorphine Stabilization and Taper Phase General Visit: 6 visits (2 visits per 
week for 3 weeks)= $240 
• Detox Week: 5 visits= $200 
• Follow-up Visits: 16 visits= $640 
Therefore, if you attend every study visit, you can earn up to approximately $1,720. We are required by 
law to report your earnings to the IRS. Therefore, your Social Security Number and amount earned will 
be reported, and you will receive the appropriate IRS form at the end of the year in which you were paid. 
Please note that payment for this study may affect your eligibility for Medicaid and other city and state 
support services. No information about which study you participated in will be provided to the IRS.  
 
IX. 
In Case of Injury  
Federal regulations require that we inform participants about our institution’s policy with regard to 
compensation and payment for treatment of research-related injuries. Please be aware that:  
1. The New York State Psychiatric Institute, Columbia University, Research Foundation for Mental 
Hygiene, and New York Presbyterian Hospital will furnish that emergency medical care determined to 
be necessary by the medical staff of this hospital.  
2. You will be responsible for the cost of such care, either personally or through your medical insurance 
or other form of medical coverage.  
3. No monetary compensation for wages lost as a result of injury will be paid to you by the New York 
State Psychiatric Institute, Columbia University, Research Foundation for Mental Hygiene, or by New 
York Presbyterian Hospital.  
4. By signing this consent form, you are not waiving any of your legal rights to seek compensation 
through the courts.  
 
X. 
Questions  
The investigators will answer to the best of their abilities any questions you may have now or in the 
future about the study procedures or about your response to the procedures. You should contact the 
Principal Investigator, Dr. Adam Bisaga, at (646)744-6155 if you have any questions. If a medical 
emergency occurs at night or over the weekend, you should go to the nearest hospital emergency room 
and have them call (914) 419-8921 and ask for the doctor on call. If you have any questions about your 
rights as a research participant, want feedback, or have a complaint, you may call the NYSPI 
Institutional Review Board (IRB). An IRB is a committee that protects the rights of human subjects in 
research studies). You may call the IRB Main Office at (646) 774-7155 during regular office hours.  
 
 
 
 
 
 


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XI. 
Documentation of Consent for Screening 
I voluntarily agree to participate in the screening for the research study described above.  
 
 
Print name : ________________________________________________  
(Participant) 
 
 
Signed: __________________________________________Date: _________________  
 
I have discussed the proposed research with this participant including the risks, benefits, and alternatives 
to participation (including the alternative of not participating in the research). The participant has had an 
opportunity to ask questions and in my opinion is capable of freely consenting to participate in this 
research.  
 
 
Print name: _______________________________________________  
(Person Designated to Obtain Consent) 
 
 
Signed: ___________________________ Date: __________________  
 
Consent for Future Contact 
You permit the Opioid Treatment Research Program staff to contact you in the future. 
 
 
Print name : ________________________________________________  
(Participant) 
 
Signed: __________________________________________Date: _________________  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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XII. 
Documentation of Consent for Study Participation 
I voluntarily agree to participate in the research study described above.  
 
 
Print name : ________________________________________________  
(Participant) 
 
 
Signed: __________________________________________Date: _________________  
 
I have discussed the proposed research with this participant including the risks, benefits, and alternatives 
to participation (including the alternative of not participating in the research). The participant has had an 
opportunity to ask questions and in my opinion is capable of freely consenting to participate in this 
research.  
 
 
Print name: _______________________________________________  
(Person Designated to Obtain Consent) 
 
 
Signed: ___________________________ Date: __________________  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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ADDENDUM 1 
CONSENT FOR SIGNIFICANT OTHER CONTACT 
 
It may be important for the staff at the clinic to discuss your problems with a close family member or friend 
to assess how you are doing, to help contact you if you miss a visit, or in case of an emergency. By signing 
this page, you consent to allow the staff to contact the following person(s) to discuss your case throughout 
the course of your treatment. You may refuse to grant this permission, and it will not affect your eligibility 
for treatment in this study.  
Name:_______________________________________Relationship:__________________ 
Address:____________________________________________________________ 
Phone Numbers:______________________________________________________ 
Name:_______________________________________Relationship:__________________ 
Address:____________________________________________________________ 
Phone Numbers:______________________________________________________ 
Name:______________________________________________________________  
 
Significant other contact information refused:____  
 
Participant Signature:_______________________ Date____________  
 
Investigator Signature:_______________________ Date____________  


Form #PP2: HIPAA Authorization for Research 4.14.14 
New York State Psychiatric Institute (NYSPI) 
Authorization to Use or Disclose Health Information during a Research Study 
Protocol Number: 
Principal Investigator: 
Name of Study: 
Before researchers can use or share any identifiable health information (“Health Information”) about you as part of the 
above study (the “Research”), the New York State Psychiatric Institute (NYSPI) is required to obtain your authorization. You agree 
to allow the following individuals and entities to use and disclose Health Information about you as described below: 
•
New York State Psychiatric Institute (NYSPI), your doctors and other health care providers, if any, and
•
The Principal Investigator and his/her staff (together “Researchers”).   Researchers may include staff of NYSPI, the New York
State Office of Mental Health (OMH), Research Foundation for Mental Hygiene, Inc. (RFMH), and Columbia University (CU),
provided such staff is a part of the study, and
•
Providers of services for the Research at CU, NYSPI and/or RFMH, such as MRI or PET, or  Central Reference Laboratories 
(NKI), if indicated in the consent form.
1.
The Health Information that may be used and/or disclosed for this Research includes:
All information collected during the Research as told to you in the Informed Consent Form.   
Health Information in your clinical research record which includes the results of physical exams, medical and 
psychiatric history, laboratory or diagnostic tests, or Health Information relating to a particular condition that is related  to 
the Research. 
Additional information may include: 
2.
The Health Information listed above may be disclosed to:
Researchers and their staff at the following organizations involved with this Research: 
The Sponsor of the Research, 
and its agents and contractors (together, “Sponsor”); and  
Representatives of regulatory and government agencies, institutional review boards, representatives of the Researchers 
and their institutions to the level needed to carry out their responsibilities related to the conduct of the research.   
Private laboratories and other persons and organizations that analyze your health information in connection with 
this study 
Other (family members or significant others, study buddies, outside agencies etc.) Specify: 
3.
By giving permission to release your Health Information as described above, you understand that your Health
Information may be disclosed to individuals or entities which are not required to comply with the federal and state privacy laws
which govern the use and disclosure of personal Health Information by NYSPI.   This means that once your Health
Laboratory Corporation of America (Lab Corp.)


Alkermes

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
Buprenorphine stabilization and induction onto Vivitrol for heroin-dependent individuals
Adam Bisaga, M.D.
7699


Form #PP2: HIPAA Authorization for Research 4.1.14 
Information has been disclosed to a third party which does not have to follow these laws (e.g., a drug company or the Sponsor 
of the Research), it may no longer be protected under the HIPAA or NYS Mental Hygiene Law requirements but is subject to the 
terms of the consent form and may be subject to other state or federal privacy laws or regulations.  
4.
Please note that:
•
You do not have to sign this Authorization form, but if you do not, you may not be able to participate in the study or
receive study related care.  You may change your mind at any time and for any reason. If you do so, you may no
longer be allowed to participate in the study.  If you withdraw this Authorization the research staff and the Sponsor, if this
is sponsored research, may still use or disclose Health Information containing identifying information they already have
collected about you as needed to maintain the reliability of the research.  Any request to withdraw this Authorization
must be made in writing to (enter name and contact information below):
•
While the Research is going on, you may not be allowed to review the Health Information in your clinical research
record that has been created or collected by NYSPI.   When this research has been completed you may be allowed to see
this information.  If it is needed for your care, your Health Information will be given to you or your Doctor.
5.
This Authorization does not have an end date.
6.
You will be given a copy of this form after you have signed it.
I agree to the use and disclosure of Health Information about me as described above: 
__________________________________________                _____________________ 
Signature of Participant/ Legal Representative    
Date 
______________________________________ 
Printed Name of Participant 
______________________________________ 
Relationship of Legal Representative to Participant (if applicable) 
We also ask you or your legal representative to initial the statements below: 
I have received a copy of the NYSPI/OMH Notice of Privacy Practices. 
Adam Bisaga, M.D.
1051 Riverside Drive, Unit 120
New York, NY 10032

SAP_001.pdf: 
Buprenorphine Stabilization and Induction onto Vivitrol for Heroin-dependent Individuals 
 
Statistical Analysis Plan 
August 17, 2017 
 
 
 
Primary objective 
Individuals dependent on heroin have low rates of successful transition onto the Vivitrol on an outpatient 
basis. We propose to evaluate novel procedure to initiate treatment with Vivitrol in this difficult to treat 
population. Participants will be stabilized on buprenorphine for three weeks followed by a rapid induction 
onto Vivitrol using escalating doses of oral naltrexone. 
 
Primary Endpoint 
The primary outcome measure will be the proportion of patients successfully retained to receive the first 
naltrexone injection (dichotomous). 
 
Secondary Objective 
It is not known which factors predict, mediate, and moderate treatment response. Therefore, we propose 
to collect additional measures that may reflect the physiological changes associated with opioid 
withdrawal and naltrexone induction as well as response to medications. We will also evaluate the impact 
of concurrent substance use on treatment outcome and finally evaluate the safety of proposed protocol 
 
Secondary Endpoint 
Secondary Outcomes: 1) The proportion of patients successfully retained to receive second and third 
Vivitrol injection (dichotomous); 2) Measures of opiate withdrawal and sleep (continuous, longitudinal); 3) 
Measures of mood and anxiety (continuous, longitudinal); 4) Adverse events and serious adverse events; 
5) A summary measure (combining urine and self-report) reflecting urine-confirmed abstinence from 
opioids and urine-confirmed abstinence from other drugs. 
 
Exploratory Objectives 
We will explore which patients are most likely to benefit from this procedure. We will evaluate the 
feasibility and acceptability of the protocol. We will evaluate whether proposed doses of adjunctive 
medications are adequate. 
 
Hypothesis 
We hypothesize that a short-term treatment with buprenorphine prior to initiating treatment with 
naltrexone will increase the proportion of heroin-dependent patients successfully inducted onto Vivitrol. 
We hypothesize that at least 65% of patients will be successfully retained to receive the first naltrexone 
injection. Based on our experience with various induction methods a response rate of less than 45% is 
too low to warrant further study of this treatment approach.   
 
Analysis Plan 
Given this is a single arm efficacy trial, most of the outcomes will be expressed as descriptive statistics. 
The primary aim is to determine if there is sufficient efficacy for the proposed procedure to warrant future 
studies.  
 
Sample Size Justification 
We believe that 30 participants will allow sufficient number to observe safety and tolerability and to 
develop precise parameters for the protocol.