Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Phase: NA
Conditions: Alcohol Use Disorder
Sponsor: VA Office of Research and Development

Study Protocol and Analysis Plan
Title: Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders 
NTC: 03191266
Date: 06/27/2025

Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026
Personnel Info .............................................................................................................
2
Participant Population .................................................................................................
3
Study Location ............................................................................................................
4
General Checklist ........................................................................................................
4
Funding .......................................................................................................................
6
Resources ....................................................................................................................
7
Purpose, Study Procedures .......................................................................................... 10
Radioisotopes or Radiation Machines ......................................................................... 18
Drugs,Devices,Reagents ............................................................................................. 19
Medical Equipment for Human Subjects and Laboratory Animals ............................ 21
Participant Population(a-g) ......................................................................................... 21
Participant Population(h-m) ........................................................................................ 23
Risks(a-e) .................................................................................................................... 25
Privacy And Confidentiality ....................................................................................... 32
Conflict Of Interest ..................................................................................................... 32
Consent Background ................................................................................................... 36
Assent Background ..................................................................................................... 39
HIPAA Background .................................................................................................... 39
Attachments ................................................................................................................. 40
Obligations .................................................................................................................. 41
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 1 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University

Protocol Director
Name
Timothy Durazzo
Degree (Program/year if
student)
PhD
Position, e.g. Assistant Professor,
Resident, etc.
Prof-Med Ctr Line
Department
Psych/Public Mental
Health & Population
Sciences
5717 (VA
151Y)
Phone
650-493-5000
x62982
E-mail
tdurazzo@stanford.edu
CITI Training current
Y
Admin Contact
Name
Timothy Durazzo
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Professor-Univ Med Line
Department
Psych/Public Mental
Health & Population
Sciences
5717
Phone
4156867609
E-mail
tdurazzo@stanford.edu
CITI Training current
Y
Investigator
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Department
Phone
E-mail
CITI Training current
Other Contact
Name
Claudia Beatriz Padula
Degree (Program/year if
student)
PhD
Position, e.g. Assistant Professor,
Resident, etc.
Instructor (Affiliated) [VAPAHCS]
Department
Psychiatry VA
Research
Phone
650-493-5000
E-mail
padula@stanford.edu
CITI Training current
Y
Academic Sponsor
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Department
Phone
E-mail
CITI Training current
Other Personnel
Name
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 2 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Jerome A Yesavage
MD
Professor
Department
Phone
(650) 852-3287
(650) 852-3297 E-mail
yesavage@stanford.edu
CITI Training current
Y
Name
Keith Humphreys
Degree (Program/year if
student)
PhD
Position, e.g. Assistant Professor,
Resident, etc.
Professor
Department
Psych/Public Mental
Health & Population
Sciences
5717
Phone
(650) 723-9067
(650) 617-2736 E-mail
knh@stanford.edu
CITI Training current
Y
Name
Laura Lazzeroni
Degree (Program/year if
student)
Position, e.g. Assistant Professor,
Resident, etc.
Professor
Department
Phone
(650) 723-0947
E-mail
Lazzeroni@stanford.edu
CITI Training current
Y
Name
Meng Gu
Degree (Program/year if
student)
PhD
Position, e.g. Assistant Professor,
Resident, etc.
Sr Res Scientist-Physical
Department
Rad/Radiological
Sciences Laboratory
5488
Phone
E-mail
mgu@stanford.edu
CITI Training current
Y
Name
Margaret Windy Mcnerney
Degree (Program/year if
student)
PhD
Position, e.g. Assistant Professor,
Resident, etc.
Department
Psychiatry VA
Research
Phone
E-mail
windymc@stanford.edu
CITI Training current
Y
Name
Arthur Noda
Degree (Program/year if
student)
MS
Position, e.g. Assistant Professor,
Resident, etc.
Research Data Analyst
Department
Psych/Public Mental
Health & Population
Sciences
Phone
(650) 493-5000
(650) 852-3297 E-mail
artnoda@stanford.edu
CITI Training current
Y
Participant Population(s) Checklist
Yes/No
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 3 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

• Children (under 18)
N
• Pregnant Women and Fetuses
N
• Neonates (0 - 28 days)
N
• Abortuses
N
• Prisoners
N
• International Participants
N
Please enter the countries separated by comma
• Impaired Decision Making Capacity
N
• Cancer Subjects
N
• Laboratory Personnel
N
• Healthy Volunteers
N
• Students
N
Stanford students N Other students N
• Employees
N
• Other (i.e., any population that is not specified above)
Y
Study Location(s) Checklist
Yes/No
• Stanford University
Y
• Clinical & Translational Research Unit (CTRU)
• Stanford Medicine Health Care
Tri-Valley
• Stanford Medicine Children's Health
• VAPAHCS (Specify PI at VA)
Y
Timothy C. Durazzo, PhD
• Other (Click ADD to specify details)
General Checklist
1. Multi-site
Yes/No
• Is this a multi-site study? A multi-site study uses the same protocol to conduct human
subjects research at more than one site.
N
2. Cooperative/Collaborative Study?
Yes/No
• Are there any collaborating institution(s)? A collaborating institution is generally an
institution that collaborates equally on a research endeavor with one or more institutions.
N
3. Cancer Institute
Yes/No
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 4 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

• Cancer-Related Studies (studies with cancer endpoints), Cancer Subjects (e.g., clinical
trials, behavior/prevention) or Cancer Specimens (e.g., blood, tissue, cells, body fluids with
a scientific hypothesis stated in the protocol).
N
4. Clinical Trials
Yes/No
• Investigational drugs, biologics, reagents, or chemicals?
N
• Commercially available drugs, reagents, or other chemicals administered to subjects that
are being studied?
N
• Investigational Medical Device / Commercial Medical Device used off-label or if being
studied?
Y
• IDE Exempt Device (Commercial Medical Device used according to label, Investigational
In Vitro Device or Assay, or Consumer Preference/Modifications/Combinations of
Approved Medical Devices)
N
• Will this study be registered on clinicaltrials.gov? ( See Stanford decision tree )
Y
• Who will register for ClinicalTrials.gov?
NCT# 03191266
N
5. Tissues and Specimens
Yes/No
• Human blood, cells, tissues, or body fluids (tissues)?
Y
• Tissues to be stored for future research projects?
Y
• Tissues to be sent out of this institution as part of a research agreement? For guidelines,
please see Material Transfer Agreements
N
6. Biosafety (APB)
Yes/No
• Are you submitting a Human Gene Transfer investigation using a biological agent or
recombinant DNA vector? If yes, please complete the Gene Transfer Protocol Application
Supplemental Questions and upload in Attachments section.
N
• Are you submitting a Human study using biohazardous/infectious agents? If yes, refer to
the https://ehs.stanford.edu/forms-tools/genome-editing-and-gene-drives-stanford
Administrative Panel on BioSafety website prior to performing studies.
N
• Are you submitting a Human study using samples from subjects that are known or likely to
contain biohazardous/infectious agents? If yes, refer to the
https://ehs.stanford.edu/forms-tools/genome-editing-and-gene-drives-stanford
Administrative Panel on BioSafety website prior to performing studies.
N
7. Human Embryos or Stem Cells
Yes/No
• Human Embryos or Gametes?
N
• Human Stem Cells (including hESC, iPSC, cancer stem cells, progenitor cells)
N
8. Veterans Affairs (VA)
Yes/No
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 5 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

• The research recruits participants at the Veterans Affairs Palo Alto Health Care
System(VAPAHCS).
Y
• The research involves the use of VAPAHCS non-public information to identify or contact
human research participants or prospective subjects or to use such data for research
purposes.
Y
• The research is sponsored (i.e., funded) by VAPAHCS.
Y
• The research is conducted by or under the direction of any employee or agent of
VAPAHCS (full-time, part-time, intermittent, consultant, without compensation (WOC),
on-station fee-basis, on-station contract, or on-station sharing agreement basis) in
connection with her/his VAPAHCS responsibilities.
Y
• The research is conducted using any property or facility of VAPAHCS.
Y
9. Equipment
Yes/No
• Use of Patient related equipment? If Yes, equipment must meet the standards established by
Biomedical Engineering (BME) (650-725-5000)
N
• Medical equipment used for human patients/subjects also used on animals?
N
• Radioisotopes/radiation-producing machines, even if standard of care? ; More Info
N
10. Payment
Yes/No
• Subjects will be paid/reimbursed for participation? See payment considerations.
Y
11. Funding
Yes/No
• Training Grant?
N
• Program Project Grant?
N
• Federally Sponsored Project?
Y
• Industry Sponsored Clinical Trial?
N
Funding
Funding - Grants/Contracts/Agreements
Funding Administered By :
VA
SPO/RRA # (if available) :
pending
Grant # (if available) :
RX002303-01A2
Funded By/Partner (include
pending) :
Department of
Veterans Affairs
RR&D
Principal Investigator :
Timothy C. Durazzo
Grant/Contract Title if different from Protocol Title :
Y
For Federal projects, are contents of this protocol consistent with the Federal proposal?
N
Is this a Multiple Project Protocol (MPP)?
N
Is this protocol under a MPP?
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 6 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Funding - Fellowships
Gift Funding
Dept. Funding
Other Funding
Resources :
a)
Qualified staff.
Please state and justify the number and qualifications of your study staff.
Qualification of PI:
Timothy C. Durazzo, PhD (PI/PD): Dr. Durazzo is a licensed Clinical Psychologist in CA, with
specialization in Clinical Neuropsychology and formal training in neuroscience and magnetic resonance
neuroimaging. He is the attending Clinical Neuropsychologist for the War Related Injury and Illness Study
Center (WRIISC) and Research Scientist for the Mental Illness Research and Education Clinical Center
(MIRECC) at the VA Palo Alto Health Care System (VAPAHCS). He concurrently holds a faculty
appointment as an Associate Professor in the Department of Psychiatry and Behavioral Sciences at Stanford
University School of Medicine. He conducts psychoeducational/therapy groups at the VAPAHCS Addiction
Treatment Services. He has have served as PI, Co-Investigator on multiple NIH and DoD grants. A major
component of his research program focuses on the neurobiological and neurocognitive consequences of
alcohol and substance use disorders, the factors that influence recovery from these conditions, and the
mechanisms promoting the relapse/remit cycle in addictive disorders. He has extensive experience in the
recruitment, screening, longitudinal cohort maintenance, fiduciary management, supervision of students,
technicians and fellows, and the day-to-day administration of federally funded grants. He has expertise in
the administration and interpretation of all proposed psychiatric, neuropsychological, and psychosocial
measures, as well as in the acquisition and processing of data from all the magnetic resonance methods
proposed in this project. The PI has received extensive training in TMS safety and administration, is
certified to administer TMS in clinical and research settings, and will deliver all TMS procedures in
conjunction with this study. He will direct the day-to-day conduct of the study, train and supervise project
personnel, consult with Drs. Yesavage and N. Williams and Ashford (as needed)to determine eligibility of
prospective participants, oversee data collection, entry and management, and conduct or supervise all
statistical analyses.
Qualifications of Other Personnel:
Jerome Yesavage, MD: Dr. Yesavage is a Psychiatrist, ACOS Mental Health, and Director of VISN 21
MIRECC at the VAPAHCS and Professor in the Department of Psychiatry and Behavioral Sciences
at Stanford University School of Medicine. Dr. Yesavage has extensive experience as PI and
Co-Investigator in clinical trials of rTMS treatment in multiple populations and in the diagnoses and
treatment of mental disorders. Dr. Yesavage will serve as a study physician for the rTMS treatment
component of this application (i.e., be available for medical emergencies and consultation) and will directly
assist the PI on supervising rTMS safety, protocol adherence, and assessment for adverse events. Dr.
Yesavage will also be involved in data interpretation, manuscript preparation, and dissemination of findings
via Posters or Presentations at professional conferences.
Keith Humphreys, PhD: Dr. Humphreys is a Career Research Scientist at the Center for Healthcare
Evaluation, VAPAHCS and Professor in the Department of Psychiatry and Behavioral Sciences at
Stanford University School of Medicine. Dr. Humphreys also co-directs the Neurochoice Initiative at
Stanford Neuroscience Institute which among other projects is using fMRI and other MR technology to
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 7 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

predict the outcome of alcohol and methamphetamine dependent Veterans in psychosocial addiction
treatment. He will assist the PI in statistical analyses, manuscript preparation and provide additional
guidance and advice on cohort maintenance and follow-up data collection. Dr. Humphreys will also be
involved in data interpretation, manuscript preparation, and dissemination of findings via Posters or
Presentations at professional conferences.
Claudia B. Padula, PhD: Dr. Padula has experience with and continues her training in behavioral and
cognitive testing, functional MRI, study design, execution and analysis via her VA Career Development
Award. She is a Research Health Scientist Specialist at the VAPAHCS and Clinical Instructor at the
Stanford University School of Medicine. Dr. Padula has extensive experience in the recruitment, screening,
longitudinal cohort maintenance, fiduciary management, supervision of students, technicians and fellow's
expertise in the administration and interpretation of all proposed psychiatric, neuropsychological, and
psychosocial measures, as well as in the acquisition and processing of data from all the magnetic resonance
methods proposed in this project.
Laura Lazzeroni, PhD: Dr. Lazzeroni is an Associate Professor and Biostatistician in the Department of
Psychiatry and Behavioral Sciences at the Stanford University School of Medicine. She will act as the
primary biostatistician and assist the PI in conducting standard and advanced survival analysis modeling,
and provide any assistance needed for the successful execution of the project's data collection and analysis.
Dr. Lazzeroni will also be involved in data interpretation, manuscript preparation, and dissemination of
findings (via Posters or Presentations) at professional conferences.
Meng Gu, PhD: Dr. Gu is an electrical engineer, magnetic resonance (MR) physicist, and research associate
at Lucas Center for Imaging and Spectroscopy in the Department of Radiology at Stanford University. He is
an expert in MR spectroscopy implementation, testing, acquisition, processing. Dr. Gu has developed novel
pulse sequences, reconstruction and quantification methods for better metabolite detection, which have been
extensively used by investigators at Stanford University and other institutions. He will be responsible for
maintaining the integrity of MR spectroscopy pulse sequences on VA scanners, and directly assist the PI in
spectroscopy volume localization, spectroscopy data quality evaluation and quality assurance, and data
processing. He will assist Dr. Furst in maintaining the integrity of structural and perfusion MR pulse
sequences on the VA 3T GE scanner. Dr. Gu will also be involved in data interpretation, manuscript
preparation, and dissemination of findings (via Posters or Presentations) at professional conferences.
Daniel Spielman, PhD: Dr. Spielman is an electrical engineer, senior magnetic resonance (MR) physicist
and Professor of Radiology at Lucas Center for Imaging and Spectroscopy in the Department of Radiology
at Stanford University. He has over 25 years of experience as a medical imaging researcher in the field of
vivo MR imaging and spectroscopy and the development of new methods of imaging metabolism within the
body. Dr. Spielman has multiple years of experience in spectroscopy studies of individuals with different
neuropsychiatric disorders. He will directly support the PI and Dr. Gu on spectroscopy data acquisition and
processing, and provide relevant updates on advancements in the acquisition and processing methods
utilized in this project.
Margaret Windy McNerney, PhD: Dr. McNearney is a postdoctoral scholar in the Stanford/VA WRIISC
Fellowship and has a submitted application for a VA Career Development Award. She has extensive
experience and current certification in the processing, genotyping and quantitation of genetic biomarkers
associated with this study.
b)
Training.
Describe the training you will provide to ensure that all persons assisting with the research are
informed about the protocol and their research-related duties and functions.
All study personnel involved in this protocol, as well as those that may join at a later point, will be given all
protocol materials, including background materials and the IRB proposal. The core study personnel, Drs.
Durazzo, Padula, Yesavage, and Research Assistants (RAs) will meet weekly to discuss the ongoing
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 8 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

research and ensure that all personnel are appraised of any updates in the protocol. Study personnel will also
communicate regularly with each other as to the progress of each person's roles and responsibilities within
the protocol. Study personnel that will be performing magnetic resonance scans at the VAPAHCS are
trained MRI technicians and will complete appropriate safety training courses required for users of those
facilities prior to scanning participants. All core study personnel will also be trained on the necessary
procedures and forms for informed consent form and participant compensation. Further, study
personnel operating at the VA will be approved by the VA to conduct research on VA premises.
c)
Facilities.
Provide the location(s) where the research will be conducted, including physical address if not
conducted on site at Stanford University, Stanford Hospital on Pasteur Dr., Lucile Packard Children's
Hospital on Welch Rd. or VAPAHCS. Describe the facilities and resources available to conduct the
research at these sites.
The facilities are available to support each component of the protocol:
Recruitment and screening: The VAPAHCS substance abuse treatment clinics and providers are available
to support recruitment and screening of patient participants. These activities will be carried-out at the
VAPAHCS MIRECC, Building 5, 4th floor or at participants' substance abuse treatment clinic at the
VAPAHCS, depending on which location is most convenient for the participant. Private interview/exam
rooms are available for this purpose at both locations.
Consent: Conducted at the VAPAHCS MIRECC, Building 5, 4th floor and/or at participants substance
abuse treatment clinic at the VAPAHCS, depending on which location is most convenient for
the participant. Private interview/exam rooms are available for this purpose at both locations.
Clinical interview, neuropsychological and behavioral testing: Conducted at the VAPAHCS
MIRECC, Building 5, 4th floor. Private interview rooms are available for this purpose. Neuropsychological
and behavioral testing will be undertaken using computerized and paper-and-pencil measures.
Transcranial Magnetic Stimulation: Conducted at the VAPAHCS MIRECC, Building 5, 4th floor. Private
treatment rooms are available for this purpose.
Neuroimaging:
Magnetic resonance scans will be conducted at the VAPAHCS. A 3 Tesla GE Discovery 750 MRI scanner
with a 32-channel head coil is available at the VAPAHCS Diagnostic Radiology Center (Bldg. 102) directly
adjacent to Building 5 (where MIRECC offices are
located). Equipment is available for measurement of patient's vital signs and other parameters for
monitoring patient safety. All MRI data will be securely transferred via the network to Dr. Durazzo's lab
space.
Genetics: The MIRECC Genetics and Translational Laboratories are in Building 7, in Dr. McNerney's Lab.
d)
Sufficient time.
Explain the time that you and your research team will allocate to perform the research activities,
including data analysis.
We expect to begin participant recruiting participants from 11/2017-06/2023 with an end date of 09/2024.
We anticipate running 100 total participants over 4 years 50 active TMS, 50 sham rTMS. With the addition
of two RAs in 11/2017, we will have sufficient personnel and physical resources to successfully execute all
Aims of this protocol.
e)
Access to target population.
Explain and justify whether you will have access to a population that will allow recruitment of the
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 9 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

required number of participants.
Subjects for the study will be identified via the VAPAHCS Addiction Treatment Services ATS for
recruitment of individuals with alcohol use disorder. Access to this population is provided via the support of
the Director of the Foundations of Recovery (FOR; the primary recruitment site), Dr. Marina
Urman-Yotam, MD (see attached letter of support). The census for ATS programs, particularly the FOR
over the past 12 months indicates it is very feasible to meet the required target number of participants. The
majority of participants will be recruited from the FOR, which is a residential treatment program; therefore,
24 hour monitoring for any adverse events will be in place as an additional layer of participant safety.
f)
Access to resources if needed as a consequence of the research.
State whether you have medical or psychological resources available that participants might require as
a consequence of the research when applicable. Please describe these resources.
If a medical adverse event should occur, study staff includes two VA physicians who are board-certified in
psychiatry (Drs. Yesavage and Ashford). Additional medical assistance will be available through the VA
TMS clinical roll-out staff RN's and physicians trained in TMS safety and adverse event management, and
VAPAHCS Emergency Department service is readily available, if needed. Immediate
psychiatric/psychological consultation will available for participants if required via Dr. Durazzo (Licensed
Clinical Psychologist) and/or Drs. Yesavage and Ashford (Board Certified Psychiatrists. Appropriate
referrals will be made when necessary in the judgment of the PI or study physicians.
g)
Lead Investigator or Coordinating Institution in Multi-site Study.
Please explain (i) your role in coordinating the studies, (ii) procedures for routine communication with
other sites, (iii) documentation of routine communications with other sites, (iv) planned management of
communication of adverse outcomes, unexpected problems involving risk to participants or others,
protocol modifications or interim findings.
1. Purpose
a)
In layperson's language state the purpose of the study in 3-5 sentences.
The purpose of this study is to evaluate the efficacy of intermittent
theta burst (iTBS) transcranial magnetic stimulation (TMS) as a
treatment for Veterans with an alcohol use disorder (AUD) to decrease
the exceedingly high rate of relapse associated with this condition.
b)
State what the Investigator(s) hope to learn from the study. Include an assessment of the importance of
this new knowledge.
At least 60% of those with AUD will experience a major relapse period
within 6
months of treatment, irrespective of the intervention
(psychosocial and/or pharmacological) employed. Consequently, the
high prevalence of AUD and relapse following treatment in Veterans is
associated with substantial resource allocation and costs for the DVA
Health Care System. Current pharmacological and psychosocial
interventions demonstrate only a moderate level of efficacy, which is
reflected in the high rate of relapse in AUD.
iTBS-TMS is a neurostimulation method that is at the forefront
of innovative, non-invasive, and safe treatments for AUD, and the
disorders that commonly co-occur with AUD. To reduce the high rate of
relapse in Veterans with AUD, it is necessary for interventions to
more effectively address the associated neurobiological dysfunction
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 10 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

and salient co-occurring conditions. Accordingly, additional 
rigorously controlled studies are required to determine if iTBS-TMS is 
an effective treatment for Veterans with AUD.
This double-blind placebo controlled project will deliver 
completely novel data on the efficacy of iTBS-TMS to promote 
sustained abstinence for Veterans with AUD during the first 6 months 
following treatment. Monthly monitoring over the
entire first 6 months following treatment is crucial, given relapse 
within the first 6 months of treatment is robustly related to poor 
psychosocial functioning over the ensuing 1-3 years. The
ultimate goal of this proposal is provide treatment that more effectively 
promotes sustained abstinence in the Veteran with AUD, as extended
abstinence is robustly associated with optimum biomedical, 
neuropsychological,psychiatric, and psychosocial recovery and
functioning.
c)
Explain why human subjects must be used for this project. (i.e. purpose of study is to test efficacy of
investigational device in individuals with specific condition; purpose of study is to examine specific
behavioral traits in humans in classroom or other environment)
The goal of this study evaluate the efficacy of iTBS-TMS as a treatment 
for Veterans with an AUD; therefore, humans must be studied.
2. Study Procedures
a)
Please SUMMARIZE the research procedures, screening through closeout, which the research
participant will undergo. Sections in the protocol attached in section 16 can be referenced, BUT do not
copy the clinical protocol. Be clear on what is to be done for research and what is part of standard of
care. For research involving collaborators, please specify the respective roles of Stanford and each
collaborator on the protocol.
PROTOCOL SUMMARY:
Please note: Stanford Co-Investigators who are currently not WOC/Staff
at the VA
(i.e., Drs. Meng Gu, Daniel Spielman, N. Williams) will not personally 
execute any study procedure at the VA Palo Alto. Stanford Co-
investigators will only be involved in processing and statistical analysis 
of de-identified neuroimaging, neuropsychological and genetic data.
1. Recruitment and screening: Participants will be recruited via VA
Palo Alto Addiction Treatment Services.
2. Informed Consent: Prior to consent, The PI, or Co-I or qualified
RA, will recheck inclusion/exclusion criteria.
3. Baseline/Pretreatment Assessment:
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 11 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

- Psychiatric Assessment
- Alcohol and Substance use
- Neurocognitive Assessment
- 3 Tesla Magnetic Resonance Neuroimaging: The study will use the 3T 
UHP system at the Cognitive and Neurobiological Imaging (CNI) facility. 
The UHP shares a common software and hardware architecture to GE's 
FDA-approved Premier system but uses a higher-performance gradient coil 
and is not FDA approved for diagnostic use and is subject to the 21 CFR 812 
investigational device(IDE) regulations as well as 21 CFR 50 and 56. The 
system has been tested by GE according to UL606001-1 and also for 
compliance with IEC 60601-
2-33 (ed 3.1) -- meeting limits and guidelines for peripheral nerve
stimulation, patient thermal, SAR limit, acoustic noise, flammability
rating UL94-5VA for safety covers, hydrostatic pressure, electrical hazards, 
dielectric strength and pinch point. The MRI scans in this study will
also utilize operational parameters within FDA guidelines for Nonsignificant
Risk thus an Investigational Device Exemption (IDE) from FDA should not be 
necessary.
- Saliva sample as described in DETAILS OF RECRUITMENT, DESIGN AND 
TREATMENT below)
4. Treatment Phase: iTBS-TMS . Active iTBS-TMS Treatment Group – will 
receive a total of 20 treatments delivered 5-6 days/week, two (2) to
(3)treatments per day,
over 2 consecutive weeks. Sham Treatment group will receive the same 
frequency and duration of treatment, without actual administration of 
iTBS-TMS. The majority
of participants will be recruited from Palo Alto VA residential treatment 
programs; therefore, 24 hour monitoring for any adverse events will be 
in place as an additional layer of participant safety.
5. Post-Treatment Phase: Within 3-4 days of completion of the
Treatment Phase, all participants will repeat neurocognitive
assessment, select psychiatric assessment measures, select alcohol and 
substance questionnaires, 3 Tesla Magnetic Resonance Neuroimaging and 
blood draw. During this time, all participants will be receiving
treatment-as-usual at the VA clinics, and scheduling of iTBS-TMS will
be arranged as not to interfere with their daily treatment curriculum.
6. Monthly Follow-ups: For 1 year following completion of
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 12 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

active/sham iTBS-TMS treatment, participants will be contacted 
monthly,via telephone or in person, to complete brief standardized 
measures of alcohol and substance use, as well as craving to assess for 
changes in these variables over the preceding 30 days. These brief 
contacts will be 15-20 min in duration and tracking
sobriety is the primary outcome measure of this study.
DETAILS OF RECRUITMENT, DESIGN AND TREATMENT 
Recruitment and screening: Potential participants from the VAPAHCS 
treatment programs will be identified based on VA
medical/clinical staff diagnoses of an alcohol use disorder without
any comorbid condition any conditions that be contraindicated for
study (e.g., taking medications that lower seizure threshold,
magnetic resonance neuroimaging contraindications, medically confirmed 
seizure disorder). Specifically, medical/clinical staff of the programs listed 
above will identify potential participants who meet eligibility criteria and
inform the patient that a research opportunity is available to them and 
offer contact information to study personnel or the participant may request 
that study personnel contact them. The study has been explained to 
clinicians via treatment team meetings, so they are familiar with eligibility 
criteria. The PI, Co-PI or qualified RA
will check inclusion/exclusion criteria based on initial eligibility
and sociodemographic data via in person screen at the treatment program 
or at the MIRECC, Building 5, 4th floor. Private interview rooms are 
available for this purpose at both locations.
Baseline/Pretreatment Assessment see section 2.a.3.b. of grant 
application:
a) Psychiatric Assessment: will use standardized measures employed in 
clinical practice and research.
b) Alcohol and Substance use: will use standardized measures employed 
in clinical practice and research. Participants will be asked to
submit a urine sample to screen for illegal/non-prescribed drug use
and/or complete a breathalyzer to screen for alcohol use.
c) Neurocognitive Assessment: will use standardized measures employed 
in clinical practice and research
d) 3 Tesla Magnetic Resonance Neuroimaging: will be conducted at the 
VAPAHCS.
e) Saliva samples: The PI, Co-PI or research assistant will collect
saliva samples at Building 5. These samples will initially be
stored in a locked cabinet in the PI or Co-Is office at VAPAHCS,
Bldg. 5. Dr. McNerney will then take possession of the participants' saliva 
samples and take them to the VA-MIRECC Genetics
Laboratory for DNA extraction, genotyping and biomarker quantitation
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 13 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

at the VA-MIRECC Translational Laboratory. These labs are located in 
Building 7 at VAPAHCS.
Design, Treatment Phase and Treatment Arms: This is a double-blind 
randomized group design, which will enroll 100 participants. After 
screening and baseline procedures, participants will be randomized to 
active or sham rTMS conditions (50 active, 50 sham); thus
participants will have a 50% probability of receiving active
treatment. Participants will receive 20 iTBS-TMS sessions over the 
course of 2 weeks. Participants will be required to be abstinent from 
alcohol and illicit substances for 5 days and demonstrate no clinically 
significant withdrawal symptoms prior to the first iTBS-TMS session.
Rationale for Brain Region Site: The left dorsolateral prefrontal
cortex DLPFC) was chosen as the rTMS stimulation site given excitatory 
transcranial magnetic stimulation to this region has been demonstrated to 
decrease cravings in non-Veterans with AUD. Additional stimulation of 
this site has been robustly shown to be associated with decreased
unipolar depressive symptomatology; depressive disorders are highly 
comorbid in Veterans with AUD.
Duration of Treatment Phase: Active iTBS-TMS Treatment Group – will 
receive a total of 20 treatments delivered 5-6 days/week.
Participants will typically receive two treatments per day (Monday-
Friday), over 2 consecutive weeks; inter-treatment interval will be
at least 2 hours. However, in the event the participant is unable to 
complete the typical two iTBS-TMS sessions per day due to participant or 
research personnel illness, scheduling issues, or other unforeseen
circumstances. There have been no adverse events reported in the 
literature implementing multiple iTBS sessions per day in any population. 
Sham Treatment group will receive the same frequency and duration of 
treatment, without actual administration of iTBS-TMS. For both the active 
and sham iTBS-TMS groups, sessions will typically be conducted prior to 
the beginning to the participants treatment day,
and at lunch, as to not interfere with their treatment-as-usual in
the VA substance treatment clinics.
Procedures for Delivery of rTMS Sessions:
1. Anatomical localization of the left DLPFC for the stimulation coil 
will be individualized for each participant and achieved through 
standardized procedures for EEG electrode placement, optimized for 
transcranial magnetic stimulation.
2. Motor Threshold MT Elicitation: Inherent to the safe and accurate 
dosing of iTBS-TMS stimulation, resting MT elicitation will be 
performed according to established protocols, which have been in 
use since 1994. This protocol is well- established as an effective 
method for MT Elicitation, widely implemented within
both sham-controlled
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 14 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

transcranial magnetic stimulation research with demonstrated safety.
MT will be calculated for all participants prior to randomization.
3. iTBS-TMS Dosing: Dosing of iTBS-TMS will be delivered at 120% of the participants active 
MT adjusted to the skull to cortex distance (via
each participants structural MRI), as this is documented to modulate the desired cortical target, and
is not associated with any adverse events. Six hundred (1200) pulses of iTBS-TMS
at 50 Hz will be utilized, consistent with standard parameters. There
will be 10 trains of 3 pulses at 50Hz every 200ms (50Hz over 5Hz), which is 30 pulses per
theta burst train. Twenty (40) trains will be delivered to achieve 1200 pulses over
approximately 6 minutes.
4. Sham Control and Blinding Methods: The sham-control and blinding methods will be the same 
as used in TMS trials in which investigator and participant blinding to group assignment was 
carefully documented and achieved in previous clinical trials conducted with Veterans at VA 
medical centers. These methods involve:
(a) the Cool-B65-Active/Placebo Coil, which functions as both an active and sham 
coil; (b) scalp electrodes; and (c) a white-noise generator. The scalp electrodes are used 
to pass a low-voltage, low-electric current (2–20mA at no more than 100V) to mimic 
the sensation of receiving actual iTBS. The white-noise generator is used to send low-
volume white noise to the subject's ears when magnetic stimulation pulses are initiated 
to hide the click noise the iTBS-TMS produces.
Post-Treatment Phase: Within 3-4 days of completion of the Treatment Phase, all 
participants will repeat neurocognitive assessment, select psychiatric assessment 
measures, select alcohol and substance questionnaires, random urine substance screen 
and alcohol breathalyzer, 3 Tesla Magnetic Resonance Neuroimaging and saliva 
sampleas described above in Baseline/Pretreatment Assessment.
Monthly Follow-ups: For 1 year following completion of the treatment phase, 
participants will be contacted monthly, via telephone or in person,
to complete a brief standardized measures of alcohol and substance use, as well as
craving to assess for changes in these variables over the preceding 30 days. These
brief contacts will be 15-20 min and tracking sobriety is the primary outcome
measure of this study.
b)
Explain how the above research procedures are the least risky that can be performed consistent with
sound research design.
All procedures will be performed by staff trained specifically for the
tasks for which
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 15 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

they are responsible. All procedures, including the iTBS-TMS, and are considered
low-risk procedures. iTBS-TMS is regarded as safe and without lasting side effects
when established
guidelines are followed. The primary serious adverse event associated with transcranial 
magnetic stimulation procedures are seizures, however, the estimated prevalence is 
very low at < 1%. In the case of transcranial magnetic stimulation-seizures, all have 
occurred during stimulation, there was no recurrence of seizures, and no incidences of 
status epilepticus. There have been no significant adverse cognitive, brain structural,
neurologic or cardiovascular sequelae reported as a result of rTMS. Seizure risk will
be minimized by careful patient selection by rigorously screening and exclusion of
participants with history of seizure disorders or other conditions and medication
use that increases risks of seizure. A seizure protocol is in place to avoid participant
injury in the unlikely event that a seizure does occur attached. Overall, the risks to
participants in this proposal are reasonable in relation to anticipated benefits, if any,
to the participants, and the importance of the knowledge that may be expected to
result.
c)
State if deception will be used. If so, provide the rationale and describe debriefing procedures. Since
you will not be fully informing the participant in your consent process and form, complete an
alteration of consent (in section 13). Submit a debriefing script (in section 16).
N/A
d)
State if photo, audio or video recording will occur. Describe what will become of the photos or
recording after use, e.g., shown at scientific meetings, erased. Describe the final disposition of the
recordings.
N/A
e)
Describe alternative procedures or courses of treatment, if any, that might be advantageous to the
participant. Describe potential risks and benefits associated with these. Any standard treatment that is
being withheld must be disclosed in the consent process and form. (i.e. standard-of-care drug, different
interventional procedure, no procedure or treatment, palliative care, other research studies).
The participants in this study will concurrently receive standard-of-care cognitive-behavioral and 
pharmacological interventions from the VAPAHCS substance treatment clinics they are enrolled in. 
There are no potential risks to the participants who receive concurrent cognitive-behavioral and any 
procedure associated with the proposed research protocol. No participant will be enrolled who is taking a 
medication that lowers seizure threshold. Risks to confidentiality will be minimized by following all 
procedures dictated by HIPAA. Of course, potential participants may decline to be involved in the study 
and receive only the
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 16 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

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For the typical subject, provide the total number of times the radioisotope and activity will be
administered (mCi) and the route of administration.
If not FDA approved provide dosimetry information and reference the source documents (package
insert, MIRD calculation, peer reviewed literature).
c)
For research radiation machine projects, provide the following diagnostic procedures:
For well-established radiographic procedures describe the exam.
For the typical subject, identify the total number of times each will be performed on a single
research subject.
For each radiographic procedure, provide the setup and technique sufficient to permit research
subject dose modeling. The chief technologist can usually provide this information.
For radiographic procedures not well-established, provide FDA status of the machine, and
information sufficient to permit research subject dose modeling.
d)
For research radiation machine projects, provide the following therapeutic procedures:
For a well-established therapeutic procedure, identify the area treated, dose per fraction and
number of fractions. State whether the therapeutic procedure is being performed as a normal part of
clinical management for the research participants's medical condition or whether it is being
performed because the research participant is participating in this project.
For a therapeutic procedure that is not well-established, provide FDA status of the machine, basis
for dosimetry, area treated, dose per fraction and number of fractions.
5. Devices
a) Please list in the table below all Investigational Devices (including Commercial Devices used off-label) if
they are being studied.
5. 1
Device Name :
MagPro X100
Describe the device and how it will be used.
The MagPro X100 and similar transcranial magnetic stimulation devices are FDA approved for 
treatment for major depressive disorder. It is considered to be non-significant risk medical 
device when all standard safety protocols are followed.
Manufacturer :
MagVenture
Risk :
Non-significant
Y
I confirm the above are true.
Rationale for the device being non-significant risk:
Transcranial magnetic stimulation is an FDA approved treatment modality for major depressive disorder.
Although the MagPro X100 and similar transcranial magnetic stimulation devices are not currently FDA
approved for alcohol use disorders, the MagPro X100 to be used in the present study is an FDA-cleared
device.
Sponsor of Project
Indicate who is responsible for submitting safety reports to the FDA:
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 19 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Y
The sponsor is the STANFORD (SU, SHC, LPCH, VA).
Please read the following:
Sponsor-Investigator Research Requirements
If you would like further information on this process and/or assistance prior to submitting your
protocol contact: The Stanford Center for Clinical and Translational Education and Research
(Spectrum) at clinicaltrials@med.stanford.edu or for cancer research contact:
ccto-regulatory@stanford.edu
Y
I have read and understand the above guidance.
Ordering, Storage and Control
To prevent the device being used by a person other than the investigator, and in someone other than a
research participant: Confirm that the device will be handled according to the SHC/LPCH policy for
Investigational New Devices or as appropriate. If no, please provide an explanation. :
Y
Confirm?
5. 2
Device Name :
3T UHP
Describe the device and how it will be used.
3T G.E. Healthcare MR system is an upgrade to
the 3T MR750 which was a commercial FDA-
approved system.
Manufacturer :
GE
Risk :
Non-significant
Y
I confirm the above are true.
Rationale for the device being non-significant risk:
The 3T Ultra-High Performance (UHP) MRI scanner from GE is an upgrade to the 3T MR750 
which was a commercial FDA-approved system. The UHP system utilizes many components from 
GE's 3T Signa Premier, including gradient drivers, power supply, transmit and receive system 
electronics, but uses a higher-performance gradient coil. The 3T UHP system is not FDA approved, 
and is subject to the 21 CFR 812 investigational device (IDE)
regulations as well as 21 CFR 50 and 56. The system has been tested by GE according to 
UL606001-1 and also for compliance with IEC 60601-2-33 (ed 3.1) -- meeting limits and guidelines 
for peripheral nerve stimulation, patient thermal, SAR limit, acoustic noise, flammability rating 
UL94-5VA for safety covers, hydrostatic pressure, electrical hazards, dielectric strength and pinch 
point. The MRI scans in this study will also utilize operational parameters within FDA guidelines 
for Nonsignificant Risk thus an Investigational Device Exemption (IDE) from FDA should not be 
necessary. In addition, the MR research being conducted requires highly specialized software that 
does not exist in the clinical MR market so it is designed and implemented by researchers at the 
CNI. Any such software will be considered investigational, will function as a non-significant risk 
device, and is subject to the 21 CFR 812 investigational device(IDE) regulations as well as 21 CFR 
50 and 56. The investigational image acquisition software will conform to FDA guidelines for MR 
safety related to heating (SAR), peripheral nerve stimulation
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 20 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

(dB/dt), and acoustic noise.
Sponsor of Project
Indicate who is responsible for submitting safety reports to the FDA:
Y
The sponsor is the STANFORD (SU, SHC, LPCH, VA) investigator.
Please read the following:
Sponsor-Investigator Research Requirements
If you would like further information on this process and/or assistance prior to submitting your
protocol contact: The Stanford Center for Clinical and Translational Education and Research
(Spectrum) at clinicaltrials@med.stanford.edu or for cancer research contact:
ccto-regulatory@stanford.edu
Y
I have read and understand the above guidance.
Ordering, Storage and Control
To prevent the device being used by a person other than the investigator, and in someone other than a
research participant: Confirm that the device will be handled according to the SHC/LPCH policy for
Investigational New Devices or as appropriate. If no, please provide an explanation. :
Y
Confirm?
b) Please list in the table below all IDE Exempt Devices (Commercial Device used according to label,
Investigational In Vitro Device or Assay, or Consumer Preference/Modifications/Combinations of
Approved Devices) to be used on participants.
6. Drugs, Reagents, or Chemicals and Devices
a) Please list in the table below all investigational drugs, reagents or chemicals if they are being studied.
b) Please list in the table below all commercial drugs, reagents or chemicals if they are being studied.
7. Medical Equipment for Human Subjects and Laboratory Animals
If medical equipment used for human patients/participants is also used on animals, describe such
equipment and disinfection procedures.
N/A
8. Participant Population
a)
State the following: (i) the number of participants expected to be enrolled at Stanford-affiliated site(s);
(ii)the total number of participants expected to enroll at all sites; (iii) the type of participants (i.e.
students, patients with certain cancer, patients with certain cardiac condition) and the reasons for
using such participants.
(i),(ii) & (iii): One hundred 100 participants are expected to be enrolled (50 active rTMS and 50 sham
rTMS) from all substance abuse clinics at the VAPAHCS, but primarily from the Foundations of
Recovery (FOR),a 30 day residential program.
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 21 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

b)
State the age range, gender, and ethnic background of the participant population being recruited.
The study will be open to males and females, regardless of race and ethnic origin, 21-65 years of age, who
are in active treatment for an AUD at the VAPAHCS. The 21-65 age range was chosen given the vast
majority of information on iTBS-TMS efficacy and safety has been obtained from this range and this is the
typical age range of Veterans seeking treatment for AUD at the VAPAHCS.
c)
State the number and rationale for involvement of potentially vulnerable subjects in the study
(including children, pregnant women, economically and educationally disadvantaged, decisionally
impaired, homeless people, employees and students). Specify the measures being taken to minimize the
risks and the chance of harm to the potentially vulnerable subjects and the additional safeguards that
have been included in the protocol to protect their rights and welfare.
Individuals with the following conditions that are associated with decisional impairment will be excluded:
History of Schizophrenia Spectrum Disorders, Bipolar Disorders, neurodegenerative diseases (e.g.,
Alzheimer disease, Parkinson's disease) active current suicidal intent or plan (patients with a previous
clinical flag for risk for suicide will be required to have an established safety plan involving their primary
psychiatrist and the treatment team before entering the clinical trial. Individuals with a lack of fluency in
English, Wechsler Adult Reading Test below the 7th percentile (i.e., moderate or greater impairment in
estimated general intelligence), females who are pregnant or actively attempting pregnancy (conservative
exclusion for magnetic resonance researchwill also be excluded from the study. Children and homeless
people will not be included. It is common for Veteran AUD and substance use samples to contain
economically and educationally disadvantaged; however, no undue influence will be exerted on these
individual and level of compensation for study participation will not be coercive. Additionally, the treatment
phase of this study will occur while participants are receiving standard-of-care treatment at the VAPAHCS,
which will permit additional on-going monitoring for any adverse events.
d)
If women, minorities, non-English speaking individuals, or children are not included, a clear
compelling rationale must be provided (e.g., disease does not occur in children, drug or device would
interfere with normal growth and development, etc.).
No children will be involved in this project as they are not in the age range of US Armed Services Veterans.
The study will be open to male and females, regardless of race, ethnic origin, and sexual preference and
identity, 21-70 years of age, who are in active treatment for an AUD at the VAPAHCS. Approximately 5%
females and 40%racial and ethnic minorities were observed among the Veteran participants in PI's previous
studies at the VA San Francisco. Given the similar demographics of Veterans at the VAPAHCS, we
anticipate a similar distribution of females and racial and ethnic minorities.
e)
State the number, if any, of participants who are laboratory personnel, employees, and/or students.
They should render the same written informed consent. If payment is allowed, they should also receive
it. Please see Stanford University policy.
It is possible that up to 15%of our participants may be current VA laboratory personnel or employees. We
do not anticipate that any Veteran participants will be current Stanford employees or students.
f)
State the number, if any, of participants who are healthy volunteers. Provide rationale for the
inclusion of healthy volunteers in this study. Specify any risks to which participants may possibly be
exposed. Specify the measures being taken to minimize the risks and the chance of harm to the
volunteers and the additional safeguards that have been included in the protocol to protect their rights
and welfare.
No healthy volunteers will be included in this study.
g)
Describe your plan to identify and recruit potential participants including who will inform them about
the study and how they will be initially contacted by the researchers (e.g., Research Engagement
services; chart review; treating physician; ads including social media posts). All final or revised
recruitment materials must be approved by the IRB before use. Contacting potential participants is
not permitted prior to IRB approval. See
https://stanfordmedicine.box.com/shared/static/8uebsdjrrqjyauanjp9i9d0gm1i480co.pdf Recruitment
Guidance for additional information.
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 22 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Potential participants from the VAPAHCS treatment programs (Foundations of Recovery and ACT
Intensive Outpatient programs)will be identified based on VA medical/clinical staff diagnoses of an alcohol
use disorder without any comorbid condition any conditions that be contraindicated for study e.g., taking
medications that lower seizure threshold, magnetic resonance neuroimaging contraindications, medically
confirmed seizure disorder. The study protocol has been explained to medical/clinical via treatment team
meetings, and they are fully cognizant of study procedures and eligibility criteria. Medical/clinical staff of
the programs listed above will identify potential participants who meet eligibility criteria and will verbally
inform them that there is a VA-sponsored treatment they may be interested in; the medical/clinical staff
offer contact information for study personnel or the participant may request to the medical/clinical staff that
study personnel contact them. In this way, the participant is self-referred to the study. The PI, VA-based
Co-Is or qualified RA will check inclusion/exclusion criteria based on initial eligibility and
sociodemographic data via in person screen at the treatment program or at the MIRECC, Building 5, 4th
floor. Private interview rooms are available for this purpose at both locations.
h)
Inclusion and Exclusion Criteria.
Identify inclusion criteria.
The study will be open to male and females, regardless of race and ethnic origin, 21-70 years of age, whoare
in active treatment for an AUD at the VAPAHCS. The 21-65 age range was chosen given the vast majority
of information on rTMS efficacy and safety has been obtained from this range and this is the typical age
range of Veterans seeking treatment for AUD at the VAPAHCS. At time of enrollment, 21-65 years
of age, meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition DSM-5)criteria for AUD,
and alcohol is self-identified as primary substance of misuse. Actively in treatment at VAPAHCS Addiction
Treatment Service, and able to read, verbalize understanding, and voluntarily sign the Informed Consent
Form prior to participation in study procedures. Participants will be accepted if taking medications
specifically for the treatment of major depressive disorders, cigarette smoking, or for other psychiatric
conditions as long as the medications are not documented to lower seizure threshold; must be stable on any
psychotropic medication for at least 1 month prior to enrollment; it would be clinically contraindicated to
require participants to discontinue such medications for research. iTBS-TMS is safely administered to
individuals who are taking psychotropic medications that do not lower seizure threshold. Participants will be
abstinent from alcohol and non-prescribed substances for at least 5 consecutive days prior to active or sham
rTMS to ensure no participant is experiencing active acute withdrawal.
Identify exclusion criteria.
Psychiatric: History of Schizophrenia Spectrum Disorders, Bipolar Disorders, a current substance use
disorder that exceeds the severity of the AUD (based on DSM-5 diagnostic criteria), active current suicidal
intent or plan (patients with a previous clinical flag for risk for suicide will be required to have an
established safety plan involving their primary psychiatrist and the treatment team before entering the
clinical trial, any form of previous rTMS or electroconvulsive treatment. Biomedical: Including, but not
limited to uncontrolled thyroid disease, unstable congestive heart failure, angina, other severe cardiac illness
as defined by treatment regimen changes in the prior 3 months, cerebrovascular accident, cancer if < 1 year
since end of treatment; unstable diabetes, COPD requiring oxygen supplementation, Alzheimer's disease,
Parkinson's disease, any biomedical implants with ferromagnetic content, neurostimulation devices, cardiac
pacemakers or any magnetic resonance contraindications, traumatic brain injury with self-reported or
observed loss of consciousness > 30 minutes, any primary or traumatically induced seizure disorder, and
alcohol-related seizure(s) in the past 30 days. General: Lack of fluency in English, Wechsler Adult Reading
Test below the 7th percentile (i.e., moderate or greater impairment in estimated general intelligence),
females who are pregnant or actively attemptingpregnancy (conservative exclusion for magnetic resonance
research), current use of any medication or substance that is documented to lower seizure threshold or has
been identified as a contraindication for rTMS treatment.
i)
Describe your screening procedures, including how qualifying laboratory values will be obtained. If
you are collecting personal health information prior to enrollment (e.g., telephone screening), please
request a waiver of authorization for recruitment (in section 15).
1) Initial screen for alcohol use disorder undertaken by the treatment program clinical staff at intake, with
the support of the
Protocol # 42600 ( Continuing Review )
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PD: Timothy Durazzo
APPLICATION FORM
Page 23 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

director. The clinical staff will offer each incoming patient with a diagnosis of AUD the opportunity to
participate in the study, and refer to the potential participant to the PI, Co-I or trained RA's study contact
number, and the PI, Co-I or trained RA's will answer/return the potential participant's call; alternately, the
potential participant can request to the clinical staff that PI, Co-I or trained RA's contact in-person at the
VAPAHCS treatment program them to further explain the study.
2) If the potential participant is interested in the study, the PI, Co-I or trained RA will then conduct an
in-person or telephone screen for study specific inclusion and exclusion criteria. We are requesting a waiver
of authorization for this recruitment process. Eligible participants will be invited to complete Informed
Consent document and enroll in the study. Ineligible participants will be immediately informed that they do
not satisfy inclusion/exclusion criteria. Ineligible participants will not be given the specific reasons why
they are not eligible in order to maintain the integrity
and security of the study inclusion/exclusion criteria. Rather, ineligible participants will be informed that
they have a current or past history of medical, physical or psychological conditions that does not permit
safeapplication of the rTMS protocol used in this study.
j)
Describe how you will be cognizant of other protocols in which participants might be enrolled. Please
explain if participants will be enrolled in more than one study.
Subjects may be part of other protocols, including neuroimaging protocols, and this would not be expected
to interfere with our protocol. However, we plan to specifically inquire with subjects as to their involvement
in other research protocols as to best safeguard the both the subject's welfare and the integrity of data
collected by us and other research groups.
k)
Payment/reimbursement. Explain the amount and schedule of payment or reimbursement, if any, that
will be paid for participation in the study. Substantiate that proposed payments are reasonable and
commensurate with the expected contributions of participants and that they do not constitute undue
pressure on participants to volunteer for the research study. Include provisions for prorating payment.
See payment considerations
Participants will not be compensated for study screening. Participants will receive a maximum of $240 for
all baseline and treatment phase and week 5 follow-up study procedures. If participants do not complete all
baseline or post-treatment visit procedures, they will receive a pro-rated amount that is lower than $200,
based on how many procedures you completed. Participants will receive an additional $50 if all monthly
contact from week 9 – 25 are completed. Total possible compensation over 1 yearis approximately $290.
The mechanism of payment will adhere to the VA mandated procedure: payment form, which the
participant can obtain cash or check at the VA Palo Alto upon completion of Baseline and Post-treatment
Visit. This rate of compensation is commensurate with other AUD research being conducted at the
VAPAHCS and the payment mechanism is used by other alcohol/substance abuse research currently
conducted at the VA Palo Alto. The total amount of payment is proportional to the participant's time and
effort and is intended to facilitate participation without adding undue influence.
l)
Costs. Please explain any costs that will be charged to the participant.
No costs will be incurred by any participant.
m)
Estimate the probable duration of the entire study. Also estimate the total time per participant for: (i)
screening of participant; (ii) active participation in study; (iii) analysis of participant data.
(i) Probable duration of study = 7 years. End date is 30 September 24. Participant recruitment will likely end
30 September 23. Final fiscal year 2024 will be devoted to data processing and analyses.
(ii)Total time per participant:
Study Phase
Estimated Participation Time
Screening:
20-30 min
Baseline:
6.5 hours, 2-4 hours/day over 1 week.
Treatment:
6.5 hours, 40 min/day,over 2 weeks
Follow-up:
Week 5, 4 hours typically over 2 days
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 24 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Follow-up Weeks 9 – 61:
4 hours
Total Active Participation Time = approx. 22 hours over 1 year.
All procedures will be conducted before or after normal ATS clinic hours, or during lunch break, to not
interfere with the patient's treatment schedule. The project will be conducted at the VAPAHCS MIRECC
Palo Alto Division, which is on the same campus as the FOR program.
(iii).)Analysis of participant data will be ongoing for baseline data and after breaking of blind in year 6.
9. Risks
a) For the following categories include a scientific estimate of the frequency, severity, and reversibility of potential
risks. Wherever possible, include statistical incidence of complications and the mortality rate of proposed
procedures. Where there has been insufficient time to accumulate significant data on risk, a statement to this
effect should be included. (In describing these risks in the consent form to the participant it is helpful to use
comparisons which are meaningful to persons unfamiliar with medical terminology.)
i. The risks of the Investigational devices.
Transcranial magnetic stimulation (TMS) device: TMS is regarded as safe and without lasting side effects
when established guidelines are followed. The primary safety concern associated with any form of
transcranial magnetic stimulation procedures are seizures, however, the estimated prevalence is very low at
< 1%. In the case of transcranial magnetic stimulation-seizures, all have occurred during stimulation, there
was no recurrence ofseizures, and no incidences of status epilepticus. All the reported seizures resolved
promptly after removalof stimulation, without medical intervention and were not associated with lasting
adverse effects. In those rare seizure cases, the motor cortex was typically being stimulated; in the proposed
study a non-primary
motor region of the cortex left DLPFC)is the stimulation site. There have been no significant adverse
cognitive, brain structural, neurologic or cardiovascular sequelae reported because of TMS. Participants
treated with rTMS may experience temporary discomfort at the site of stimulation due to depolarization of
sensory and motor neurons in the scalp under the point of stimulation. Muscle tension headache may result
in some participants estimated to occur in less than 10%%of sessions, and can persist for 1-2 hours post
stimulation. rTMS treatment can result in mild to moderate headaches in approximately 15% of participants.
These headaches are never disabling or persistent and usually respond to ibuprofen or
acetaminophen. The incidence of headaches in those with serial transcranial magnetic stimulation typically
diminishes with increasing number of sessions. In some people, particularly those with a history of a history
of Bipolar Disorder I or II, daily transcranial magnetic stimulation caused them to experience mania
increased energy, no need for sleep, and racing thoughts; this study will exclude for a history of cyclothymia
and Bipolar Disorders.
Magnetic Resonance Neuroimaging: The magnetic resonance scanning devices (3 Tesla, General Electric
MR750) used in scanning at the Stanford Center for Cognitive (CNI)and Neurobiological Imaging poses a
non-significant risk to subjects in line with the criteria for exception from an IDE, and routinely used by
many other investigators at Stanford. There have been no serious adverse events incurred during scanning at
the Stanford CNI.
ii. The risks of the Investigational drugs. Information about risks can often be found in the
Investigator's brochure.
N/A
iii. The risks of the Commercially available drugs, reagents or chemicals. Information about risks can
often be found in the package insert.
N/A
iv. The risks of the Procedures to be performed. Include all investigational, non-investigational and
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 25 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

non-invasive procedures (e.g., surgery, blood draws, treadmill tests).
Saliva collection. There are no known risks to the participant associated with saliva collection.
Cognitive, Psychiatric and Alcohol/drug Assessments and Questionnaires. Memory and cognitive testing
can cause anxiety or frustration. The level of psychological stress is similar to what would be associated
with a clinical neuropsychological assessment.
Genetic and Biomarker testing. Genetic testing will be conducted on the collected blood samples. Samples
will be brought to our research center's lab at VAPAHCS Dr. Windy McNerney, who will conduct all
biomarker and genotyping analyses/assays,
iTBS-TMS risks are described above in 9.i. Investigational devices. Magnetic Resonance Neuroimaging
risks are described above in 9. i. Investigational device.
v. The risks of the Radioisotopes/radiation-producing machines (e.g., X-rays, CT scans, fluoroscopy)
and associated risks.
N/A
vi. The risks of the Physical well-being.
See above devices and procedures. No other risks to physical well-being are anticipated.
vii. The risks of the Psychological well-being.
Screening, neuropsychological, psychiatric interviews and questionnaires: The screening interview,
neuropsychological and psychiatric assessments, as well as self-report questionnaires may be fatiguing
and/or distressing for some individuals. Study participants will be informed that they are free to decline to
answer any questions or to stop the assessments at any time. Neurocognitive and psychiatric interview
sessions will include breaks. In the event that a study participant appears to be under undue strain, the test
or interview session will be discontinued.
Genetic Biomarker and Genetic testing: It is possible that biomarker and genetic testing could cause minor
psychological stress in a some individuals. All participants will be informed that only members of the
research staff will see results of the biomarker and genetic testing which will be in a coded format with no
individual identification. The biomarker and genetic testing is strictly for research purposes only and results
of the genetic testing will not be released to anyone outside of the research project including participants,
family, physician, or any other third party.
viii. The risks of the Economic well-being.
No risks to economic well-being are anticipated.
ix. The risks of the Social well-being.
No risks to social well-being are anticipated.
Overall evaluation of Risk.
Low - innocuous procedures such as phlebotomy, urine or stool collection, no therapeutic agent, or safe
therapeutic agent such as the use of an FDA approved drug or device.
b)
If you are conducting international research, describe the qualifications/preparations that enable you
to both estimate and minimize risks to participants. Provide an explanation as to why the research
must be completed at this location and complete the International Research Form. If not applicable,
enter N/A.
N/A
c)
Describe the planned procedures for protecting against and minimizing all potential risks. Include the
means for monitoring to detect hazards to the participant (and/or to a potential fetus if applicable).
Include steps to minimize risks to the confidentiality of identifiable information.
Screening, neuropsychological, psychiatric interviews and questionnaires: Participants will be informed that
these procedures may be fatiguing and/or distressing for some individuals. Study participants will be
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 26 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

informed that they are free to decline to answer any questions or to stop the assessments at any time.
Neurocognitive and psychiatric interview sessions will include breaks. In the event that a study participant
appears to be under undue strain, the test or interview session will be discontinued. Participants will be
reminded that they are free to withdraw from participation at any time.
iTBS-TMS administration: The iTBS-TMS operator will be the PI (Dr. Durazzo) or a RA specifically
trained by Dr. Durazzo. The PI is fully trained and qualified to administer the procedure according to
current safety practices and standards of care in research and clinical settings. Co-Is trained in rTMS (Drs.
Yesavage, Ashford) will closely monitor the PIs and RAs adherence to safety protocols and administration
for this proposal. This application employs all current established and standard iTBS-TMS treatment safety
and monitoring for adverse events guidelines.
The iTBS-TMS operator will monitor all participants for ear protection, coil placement, and seizure activity
during all sessions. All participants will be required to have abstained from alcohol or non-prescribed
medication for 5 consecutive days prior to the first rTMS session. Prior to the first iTBS-TMS session,
participants will be administered the Clinical Institute Withdrawal Assessment for Alcohol-Revised and
must score < 8; scores > 8 are indicative of potential autonomic instability); participants with a score > 8
will immediately be escorted to their VAPAHCS Addiction Treatment Services clinic for further evaluation.
Participants will be randomly screened x6 for alcohol (breath alcohol) and substance use (urine
toxicology) prior to rTMS sessions during the 2 week treatment phase. If a participants test positive or
report any alcohol or substance use during the 2 week rTMS treatment period, they will be immediately
withdrawn from the study. Additionally, prior to each participants will complete a rTMS screen, including
inquiring about any changes in medications or comorbid medical conditions, amount of sleep, and suicide
screening questionnaire prior to each rTMS session to assess for current suicide
risk. Although patients in the are regularly screened for alcohol and substance use and suicide risk while in
treatment, we will conduct random alcohol/substance screening and pre-rTMS session suicide risk
assessment to ensure participant welfare. Should a headache or site discomfort occur, these symptoms
usually readily respond to acetaminophen or ibuprofen. Any reported painfulness typically improves over
time or completely remits. To protect against possible hearing damage, participants will wear ear protection
during rTMS sessions (foam ear plugs and noise attenuating headphones. This will greatly reduce the
possibility of hearing loss. Hearing acuity testing pre-and-post rTMS is no longer a standard practice, given
the remote likelihood of rTMS-related hearing loss.
Additional Procedures for the Monitoring of Seizures and Suicidal Ideation/Behavior:
Screening, Baseline and Treatment Phase: In the unlikely event that a seizure does occur, participants will
be closely monitored and treated for any medical or psychological consequences. rTMS sessions will be
conducted at the VAPAHCS MIRECC, which fully equipped to safely handle a seizure. If at any point
during study participation, a participant has a seizure, the participant will be withdrawn from the study
immediately although they will still be followed for protocol assessments. All seizures will be considered
serious adverse events (SAE) and as such, will be reported to the study PI. We will immediately suspend
enrollment if 10 participants experience a seizure during study participation, and request that the Data
Monitoring Safety Board (DMSB)evaluate the SAE data, to determine if enrollment of new participants
should be resumed without protocol changes, if protocol modifications should be made before resuming
enrollment, or if the study should be terminated. We recognize that study termination or modification based
on SAEs, such as seizures, ultimately rests with the DMSB and the study PI. If a participant expresses
suicidal ideation/intent, and is determined to be a risk to self, a clinical evaluation will be immediately
conducted by the PI (a licensed clinical psychologist), Co-Is ((board certified psychiatrists) or by the
participant's individual mental health provider, and/or a mental health emergency clinician. The participant
will remain with qualified study personnel or a MIRECC clinician until the evaluation has been completed
and a decision made about disposition in conjunction with the Chief of Mental Health Outpatient Clinic or
the emergency mental health clinician.
Follow-up Phase: If a participant discloses active suicidal or homicidal ideation or other clinically
significant psychiatric symptomatology during the follow-up phase of the study, they will provided with the
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 27 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

number and encouraged to call Veterans Crisis Hotline or present to a local hospital emergency department.
In the event of a seizure (or other medical issues possibly secondary to rTMS, the participant will be
requested to immediate contact their primary health care provider. In the event of disclosure of the above
psychiatric emergencies or a seizure, the PI or psychiatrist Co-Investigator will also be immediately notified
and will contact the participant for further assessment and determine the appropriate intervention. If a
participant discloses that they relapsed during the follow-up period, they will be encouraged to recontact
VAPAHCS Addiction Treatment Services for re-evaluation and possible re-engagement in treatment.
Magnetic Resonance (MR)Studies: Participants will be informed of risks, using the text provided and
required by Stanford University's Institutional Review Board the VA. Our Research Assistants (RA) have
been trained by the PI, CO-Is carefully pre-screen each participant for MRI safety before the MRI
appointment. RA also have been certified to independently operate the CNI magnetic resonance scanner by
qualified CNI personnel. Minimal risks are associated with MR scanning and 3T MR scanners are now
routinely used in clinical practice. Study participants who have metal implants, cardiac pacemakers, metal
fragments or a known tendency for claustrophobia will not be admitted to the study. Study participants will
be scanned with a metal detector before entering the 3T scanner room, and all metal objects will be
removed. There is a remote possibility that the magnet will attract a metal object, producing physical
injury. To make certain
such event do not occur, the door to the magnet room is closed and there is a metal detector outside the door
to ensure no ferromagnetic metals are allowed into the scanner. One theoretical hazard of the experiments is
heating of the body due to radio waves, but the machine has several safety devices to prevent such an
occurrence. There is also a slight risk of nerve stimulation during a portion of the procedure. While there are
safety devices that prevent such events, this can occur in rare cases. To reduce this risk, volunteers will be
instructed to avoid skin-to-skin contact between their extremities, such as clasping their bare hands or
crossing their bare feet. In any case, such sensation is temporary and harmless. Fatigue, boredom, feelings
of claustrophobia, or discomfort due to loud banging sounds of gradient coils may accompany the MR
procedures. Earplugs and supplied MR-safe headphones will be used during MR scanning. A
communication system is set up inside each scanner so that study participants can contact the researchers at
any time, and will be immediately removed from the scanner upon request. A communication system is set
up inside each scanner so that study participants can contact the researchers at any time, and will be
immediately removed from the scanner upon request. In case of adverse effects, medical intervention can be
provided by Stanford Emergency Department staff. Study physicians will be available in the case of an
adverse event to debrief with the participant.
Identification of clinically significant psychiatric symptomatology other than suicidal ideation or plan), or
neurocognitive abnormalities: Although unlikely, it is possible that during the screening process, on the
psychiatric interview and questionnaires or during other study procedures, participants may manifest or
disclose clinically significant psychiatric symptoms (e.g., homicidal ideation, hallucinations) or disorders
that were not previously identified/diagnosed by VAPAHCS Addiction Treatment Services staff. In this
case, the participant will be immediately assessed by the PI a licensed clinical
psychologist/neuropsychologist, the participant's individual mental health provider, or a mental health
emergency clinician. The participant will not be left alone until the evaluation has been completed and a
decision made about disposition in conjunction with the Chief of Mental Health Outpatient Clinic, or the
emergency mental health clinician. If any participant manifests grossly clinically significant neurocognitive
impairment > 2 standard deviations below mean performance of the normative reference group)on any
domain of functioning, Dr. Durazzo will debrief the participant and inform his current mental health
treatment providers, with the participant's explicit approval and written consent obtained in the informed
consent) for further assessment. If a participant discloses that they relapsed during the follow-up period,
they will be encouraged to recontact VAPAHCS Addiction Treatment Services for re-evaluation and
possible re-engagement in treatment.
Loss of confidentiality: Every precaution will be taken to minimize loss of confidentiality. A triple lock
system will be maintained: within a locked lab, locked office, and locked file cabinet. All electronic data
will be secured on an encrypted, password-protected database behind a VA or Stanford RedCap firewall.
The participant's name will not be used in any reports or publications resulting from this study. The
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 28 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

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The role of the DSMC or DSMB is to ensure the safety of participants by analyzing pooled data from
all sites, and to oversee the validity and integrity of the data. Depending on the degree of risk and the
complexity of the protocol, monitoring may be performed by an independent committee, a board
(DSMC/DSMB), a sponsor's Data Safety Committee (DSC), a Medical Monitor, a sponsor's safety
officer, or by the Protocol Director (PD).
Describe the following:
1. What type of data and/or events will be reviewed under the monitoring plan, e.g. adverse events,
protocol deviations, aggregate data?
Although this study protocol is low risk, and will enroll a modest number of participants, we will create
a DSMB as we believe this is consistent with best clinical practices. Types of data and events that will
be reviewed are: 1) Aggregate Data Analysis Reports; 2) Progress toward Study endpoints; 3))AEs,
SAEs and unanticipated problems;)4) Protocol deviations.
2. Identify who will be responsible for Data and Safety Monitoring for this study, e.g. Stanford
Cancer Institute DSMC, an independent monitoring committee, the sponsor, Stanford investigators
independent of the study, the PD, or other person(s). a style='font-style:italic;color:#0000CC'
href=https://researchcompliance.stanford.edu/eprotocol/ephelp_dsmp#dsmp2 more...
The grant will utilize a DSMB that will review the progress of the study. The DSMB will monitor
patient enrollment, aggregate outcomes, adverse events, and other issues related to patient safety. The
safety monitoring plan reflects the low risk of the rTMS intervention, the 2-week duration of
intervention, the extra precautions taken (e.g. MRI safety screening and exclusions of individuals with a
risk of seizure, the modest number of subjects involved, and the single-site nature of the study.
3. Provide the scope and composition of the monitoring board, committee, or safety monitor, e.g.,
information about each member's relevant experience or area of expertise. If the Monitor is the
Stanford Cancer Center DSMC or the PD, enter N/A.
The composition will include a Senior VA neuroscientist scientist and senior VA neurologist, who are
have experience in the procedure used in this study and not affiliated with the study.
4. Confirm that you will report Serious Adverse Events (SAEs), Suspected Unexpected Serious
Adverse Reactions (SUSARs), or Unanticipated Problems (UPs) to the person or committee
monitoring the study in accordance with Sponsor requirements and FDA regulations.
All SAEs will be reported within 24 hours of learning of the SAE. Unanticipated problems involving
risks to participants or others will be reported within 5 days.
5. If applicable, how frequently will the Monitoring Committee meet? Will the Monitoring
Committee provide written recommendations about continuing the study to the Sponsor and IRB?
Given the modest number of participants studied per year (approximately 25, the DSMB will meet once
per year to review data reports prepared by the PI's research team. Any member of the DSMB can ask
for an emergency meeting of the group. The DSMB will issue written reports to the PI on the safety and
progress of the trial. The report will include recommendations to the PI concerning continuation,
termination or other modifications of the trial based on the observed beneficial or adverse effects of the
treatment under study. The PI will provide of the DSMB reports to the IRB.
6. Specify triggers or stopping rules that will dictate when the study will end, or when some action
is required. If you specified this in Section 2g [Study Endpoints], earlier in this application enter
'See 2g'.
See 2g
7. Indicate to whom the data and safety monitoring person, board, or committee will disseminate
the outcome of the review(s), e.g., to the IRB, the study sponsor, the investigator, or other officials,
as appropriate.
See 2g
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 31 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

8. Select One:
The Protocol Director will be the only monitoring entity for this study.
Y
This protocol will utilize a board, committee, or safety monitor as identified in question #2 above.
10. Benefits
a)
Describe the potential benefit(s) to be gained by the participants or by the acquisition of important
knowledge which may benefit future participants, etc.
iTBS-TMS could potentially generate substantial health benefits for VHA patients.
Repetitive iTBS-TMS may offer a viable and more efficacious treatment option for
Veterans with AUD. Moreover, it could bedisseminated and delivered to both urban
as well as to rural
facilities, and in VA Hospitals as well as Community Based Outpatient
Clinics (CBOC's. In sum, iTBS-TMS has the potential to dramatically
improve access to effective mental and cognitive health and
rehabilitation for a large number of Veterans with AUD. For these
reasons, the anticipated risks are reasonable in relation to the
anticipated benefits to study participants. However, if shown safe and effective,
the budgetary cost of rTMS will likely be an important
consideration relating to its subsequent evaluation and
implementation. If our hypotheses are confirmed, replicated in
independent samples, and critically evaluated by peer review, the
VAPAHCS Mental Illness Research and Education Clinical Center MIRECC
is well-suited to lead a nationwide roll-out of an iTBS-TMS treatment
protocol for AUD. The VAPAHCS MIRECC has developed treatment protocols and
led highly successful nationwide roll-outs of evidence-based practices (EBP) of
cognitive-behavioral therapy for depression and insomnia to well over 2000 VA
clinicians. VISN-21 MIRECC Education Core currently is funded for core resources
for such tasks. The VISN-21 MIRECC has been funded a roll-out for TMS for
depression concurrent with the conclusion of CSP 556 "The Effectiveness of rTMS
in Depressed VA Patients." Thus, the findings and protocol for our iTBS-TMS
intervention for AUD can be readily disseminated to VA (and non-VA)researchers,
clinicians, and leadership through the MIRECC EBP program. In clinical research
studies at VAs and universities
throughout the nation, multiple forms of rTMS are currently routinely and safely
administered by trained non-medical personnel, under the supervision of qualified
medical professionals. As described in this proposal, iTBS-TMS is a very safe
treatment when standard safety protocols are followed. Therefore, it is highly
feasible that rTMS can be safely and effectively implemented at both VA medical
centers and CBOCsto treat AUD by trained non-medical technicians under the
supervision of qualified medical personnel. This will significantly increase Veteran
access to the rTMS intervention throughout the VA system and substantially
reduce the costs of treatment delivery.
11. Privacy and Confidentiality
Privacy Protections
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 32 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

a)
Describe the setting and method (e.g. crowded waiting room, patient exam room, telephone or email
communication) in which interactions will occur and how the privacy interests of participants will be
maintained. Note, high risk data such as PHI must be sent via "Secure:" email per
https://uit.stanford.edu/security/hipaa/email-policy Stanford policy.
During the consenting process, in-person screening, and the collection of other
study data, participants will meet in a private interview room with a member of the
study team at the study site Bldg 5 at VAPAHCS). Saliva samples will be obtained
in a private setting at the study site Bldg. 5, VAPAHCS.
Confidentiality Protections
b)
Specify PHI (Protected Health Information). PHI is health information linked to HIPAA identifiers
(see above). List BOTH health information AND HIPAA identifiers. If you are using STARR, use the
Data Privacy Attestation to ensure that your request will match your IRB-approved protocol. Be
consistent with information entered in section 15a.
We will collect the following HIPAA identifiers, as mentioned on
the VA HIPAA form:
- Social security number for participation compensation i.e., participant payment,
and entry of required research notes
into VA medical records;
- Name, address and telephone number for follow-up assessments and to
mail participation compensation;
and to mail payment;
- Birth dates & visit dates.
We will collect the following PHI, as mentioned on the HIPAA:
- Demographic information including age and race/ethnicity;
- Results of past routine laboratory tests;
- Physical examinations and related past medical records;
- Magnetic resonance neuroimaging data, MRI digital images and
clinical reads of MRIs;
- Research data, questionnaires, saliva specimens, and study progress
notes, which may include: cognitive test scores; questionnaires about mood and
everyday function; current and past medical history; current and past medications;
adverse effects during the study; and height and weight.
c)
You are required to comply with University Policy that states that ALL electronic devices: computers
(laptops and desktops; OFFICE or HOME); smart phones; tablets; external hard disks, USB drives,
etc. that may hold identifiable participant data will be password protected, backed up, and encrypted.
Stanford University IT approved platforms (https://uit.stanford.edu/guide/riskclassifications
https://uit.stanford.edu/guide/riskclassifications) should be used for data management. Consult with
your Department IT representative for more information.For data security policies and links to
encrypt your devices see http://med.stanford.edu/irt/security and
target=_blankhttp://www.stanford.edu/group/security/securecomputing/mobile_devices.html.
Additionally, any PHI data on paper must be secured in a locked environment.
By checking this box, You affirm the aforementioned. Y
Paper data with PHI will be kept in locked file cabinets in locked
offices. Data collected on paper forms and questionnaires will be
entered into encrypted, password-protected databases. Electronic
files and databases are maintained on a secure VA network,
on a server that is backed up and located in a secure server
room accessible only by authorized personnel. Only staff listed
for a given protocol are granted access to appropriate server folders. Staff's
computers are password protected, encrypted, and backed up. The VA prohibits
removable drives. At the VA, REDCap data are transmitted from behind the VA
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 33 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

firewall (on the VA intranet) and
REDCap servers are housed at the VA Informatics and Computing
Infrastructure (VINCI). VINCI servers are physically located at
the VA Austin Information Technology Center (AITC), located in Austin, Texas. VA
REDCap is only available to VA researchers through a web URL that requires a VA
generated login and email address.
Each subject will be assigned a participant ID number (PID). All
computer-entered data will be coded using PIDs only.
Biomarker/genetic information is stored in a separate password
protectefile, which can only be accessed by the PI, Co-PI ,the data
manager/analyst, and appropriately delegated staff. Only the data
manager/analyst can match genetic information with the participant
ID number. The genetic data is only used for analysis of data
conducted by the PI or data manager in this study unless the
subject or LAR consents to future use and sharing of genetic data
and samples as documented on the informed consent form.
All personnel involved in this study will have successfully completed
applicable VA and Stanford training. All subject-level identifiable
data will be treated as Protected Health Information (PHI) unless that data does
NOT contain any of the data elements that HIPAA considers protected. Any data,
specimens,forms, reports, and other records that leave the site will be identified
only by a participant id number (PID) to maintain confidentiality. Information will
not be released without written permission of the participant, except as necessary
for monitoring by the IRB.
d)
Describe how data or specimens will be labeled (e.g. name, medical record number, study number,
linked coding system) or de-identified. If you are de-identifying data or specimens, who will be
responsible for the de-identification? If x-rays or other digital images are used, explain how and by
whom the images will be de-identified.
Data, specimens and image files will be labeled by a participant ID
number (PID). Information linking the PID code and PHI will be kept
on a secure, password protected computer behind a firewall. The Data
Manager is responsible for de-identification of data. The PI is
ultimately responsible for de-identification of samples.
e)
Indicate who will have access to the data or specimens (e.g., research team, sponsors, consultants) and
describe levels of access control (e.g., restricted access for certain persons or groups, access to linked
data or specimens).
Data, specimens and image files will be labeled by a participant ID
number (PID). Information linking the PID code and PHI will be kept on a secure,
password protected computer behind a firewall. The Data
Manager is responsible for de-identification of data. The PI is
ultimately responsible for de-identification of samples.
f)
If data or specimens will be coded, describe the method in which they will be coded so that study
participants' identities cannot be readily ascertained from the code.
Members of the research team will have access to all non-genetic data. The data
manager has access to both non-genetic and genetic
data; however, the data manager has no access to subject names, SSNs,
or contact information. If the participant requests explicitly in
writing, we will send information about neuropsychological assessments and
clinical results to his/her the medical or mental health care provider of their choice.
De-identified study data may be shared with collaborating researchers at Stanford
University and at other institutions. De-identified data may also be shared with
collaborating researchers at other institutions in the future. No genetic data (other
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 34 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

than de-identified genotype or de-identified quantitated plasma/serum results)
and physical biomarker specimens will be shared with anyone outside of this
research study unless the subject or legally authorized representative consents
future use and sharing of genetic data and samples as documented on the
informed consent document.
g)
If data or specimens will be coded, indicate who will maintain the key to the code and describe how it
will be protected against unauthorized access.
A participant ID number PID is assigned to a subject after they sign a consent
form. This numeric code is independent of any identifying
information.
h)
If sharing data with others, describe how data will be transferred or transmitted (e.g., file transfer
software, file sharing, email). If transmitted via electronic networks, confirm a Stanford University IT
approved platform will be used (see https://uit.stanford.edu/guide/riskclassifications
https://uit.stanford.edu/guide/riskclassifications) or that data will be encrypted while in transit.
Additionally, confirm appropriate agreements are in place to allow for the sharing (see
https://ico.stanford.edu/stanford-researchers/who-will-handle-my-agreement
https://ico.stanford.edu/stanford-researchers/who-will-handle-my-agreement). If using or sharing PHI,
refer to the following policies: https://uit.stanford.edu/security/hipaa
https://uit.stanford.edu/security/hipaa.
No PHI will be transferred to any person/organization outside of the
or VA research team.
i)
How will you educate research staff to ensure they take appropriate measures to protect the privacy of
participants and the confidentiality of data or specimens collected (e.g. conscious of oral and written
communications, conducting insurance billing, and maintaining paper and electronic data)?
All research staff will complete and remain current with all required
VA and Stanford training prior to working with human subjects. The PI, along with
VA Research Administration, also reinforce the importance of maintaining
confidentiality.
12. Potential Conflict of Interest
Investigators are required to disclose any outside interests that reasonably appear to be related/li to this protocol.
Outside Interest Tasks
Investigators
Role
Potential
COI?
Date
Outside
Interest
Answered
Date OPACS
Disclosure
Submitted
COI Review
Determination
Timothy
Durazzo
PD
N
01/27/2025
N/A
Claudia Beatriz
Padula
OC
N
01/27/2025
N/A
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 35 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Keith
Humphreys
OP
N
01/27/2025
N/A
Laura
Lazzeroni
OP
N
01/27/2025
N/A
Jerome A
Yesavage
OP
N
01/27/2025
N/A
13. Consent Background
13. 1
Waiver of Documentation
Screening Waiver of Documentation
Check if VA related
Y
a)
Describe the informed consent process. Include the following.
i) Who is obtaining consent? (The person obtaining consent must be knowledgeable about the study.)
ii) When and where will consent be obtained?
iii) How much time will be devoted to consent discussion?
iv) Will these periods provide sufficient opportunity for the participant to consider whether or not to
participate and sign the written consent?
v) What steps are you taking to minimize the possibility of coercion and undue influence?
vi) If consent relates to children and if you have a reason for only one parent signing, provide that
rationale for IRB consideration.
Qualified research personnel will conduct this screen to determine basic eligibility. We believe it is an
excessive burden on the potential participant to require participants to complete the entire informed consent
to conduct this brief screen for study eligibility. It will be administered prior to obtaining written informed
consent, but after the potential participants have already expressed interest and willingness to provide study
personnel to contact them.
b)
What is the Procedure to assess understanding of the information contained in the consent? How will
the information be provided to participants if they do not understand English or if they have a hearing
impairment? See HRPP Chapter12.2 for guidance.
The purpose of the screening interview is given in the script preceding screening. Participant oral assent will
be obtained for this screening interview. VA waiver of HIPAA authorization for recruitment has also been
included in the protocol.
c)
What steps are you taking to determine that potential participants have the capacity to participate in
the decision-making process? If your study may enroll adults who are unable to consent, describe (i)
how you will assess the capacity to consent, (ii) what provisions will be taken if the participant regains
the capacity to consent,(iii) who will be used as a legally authorized representative, and (iv) what
provisions will be made for the assent of the participant.
The clinical staff who refer patients to the study will be asked if the patient has capacity to consent for the
study. In addition, if it appears that a patient does not understand the consent procedure or does not have the
capacity to consent to screening, we will not screen them for participation in the study.
Additional VA questions:
i)
List the people to whom you have formally delegated responsibility to obtain informed consent, and
state whether they have the appropriate training to perform this activity.
The PI, VA Co-I or qualified VA research staff have responsibility of obtaining oral assent prior to
conducting the screening interview individuals for the study.
ii)
Will legally effective informed consent be obtained from the participant or the participant's legally
authorized representative (LAR) or both? If LAR, is it clear who can serve as LAR?
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 36 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

N/A
iii)
Will the circumstances of the consent process minimize the possibility of coercion or undue influence
and provide the prospective participant or their representative sufficient opportunity to consider
whether to participate?
Potential participants will be given information about the study and it will be made clear that participating in
the screening interview is completely voluntary and choice of participation will not affect their current or
future VA treatment in any manner.
iv)
Will the circumstances of the consent process minimize the possibility of coercion or undue influence?
Patients screened for participation will be explicitly informed that completing the screening interview is
completely voluntary and there will be no compensation for the screen. The participants are told there is no
compensation for the screening interview.
v)
Will the information being communicated to the participant or the representative during the consent
process exclude any exculpatory language through which the participant or the representative is made
to waive or appear to waive the participant's legal rights, or release or appear to release the
investigator, the sponsor, the institution, or its agent from liability for negligence (e.g. I give up any
property rights I may have in bodily fluids or tissue samples obtained in the course of the research)?
No.
vi)
Please confirm the following:
a. A witness to the participant's signature or the participant's legally authorized representative's
signature will sign and date the consent document.
b. If the sponsor or the IRB requires a witness to the consenting process in addition to the witness to
the participant's signature and if the same person is needed to serve both capacities, a note to that
effect is placed under the witness's signature line.
c. A copy of the signed and dated consent document will be given to the person signing the consent
document.
d. The consent form is on the VA Form 10-1086.
Select ALL applicable regulatory criteria for a Waiver of Documentation and provide a protocol-specific
justification:
1)
45 CFR 46.117(c)(1)(i)., that the only record linking the participants and the research would be
the consent document, and the principal risk would be potential harm resulting from a breach
of confidentiality; each participant (or legally authorized representative) will be asked whether
he/she wants documentation linking the participant with the research, and the participant's
wishes govern.
2)
Y
45 CFR 46.117(c)(1)(ii)., that the research presents no more than minimal risk of harm to
participants and involves no procedures for which written consent is normally required outside
of the research context.
3)
45 CFR 46.117(c)(1)(iii)., if participants or legally authorized representatives (LAR) are
members of a distinct cultural group in which signing forms is not the norm, the research
presents no more than minimal risk and there is an appropriate alternative mechanism for
documenting that informed consent was obtained.
4)
Y
21 CFR 56.109(c)(1)., presents no more than minimal risk of harm to participants and involves
no procedures for which written consent is normally required outside of the research context.
Rationale for above selection:
We believe it is an excessive and unreasonable burden on the potential participant to require those
with a potential history of bipolar/cyclothymia or schizophrenia-spectrum disorders to complete the
entire lengthy informed consent process to conduct this brief screen for study eligibility. Such
individuals would be immediately excluded after reading through the entire consent, which would
likely be highly frustrating for many potential participants. We request the IRB consider the patient
population of this study and our desire to minimize any unnecessary burden on potential participants.
13. 2
Consent
Informed Consent
Check if VA related
Y
a)
Describe the informed consent process. Include the following.
i) Who is obtaining consent? (The person obtaining consent must be knowledgeable about the study.)
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 37 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

ii) When and where will consent be obtained?
iii) How much time will be devoted to consent discussion?
iv) Will these periods provide sufficient opportunity for the participant to consider whether or not to
participate and sign the written consent?
v) What steps are you taking to minimize the possibility of coercion and undue influence?
vi) If consent relates to children and if you have a reason for only one parent signing, provide that
rationale for IRB consideration.
(i) Study personnel obtaining consent will be one of the investigators, or RA, who have been trained to give
informed consents. (ii)The consenting is always done after the potential research subject has been presented
with a description of the study and indicated interest in participating, and before any information is
collected, or any questionnaires answered. The consenting will typically takes place in one of the private
interview rooms in the VAPAHCS MIRECC Bldg 5, 4th floor or at the participants VAPAHCS Addition
Treatment Program. (iii)Sufficient time will be allowed for participants to read the consent and to ask any
and all questions they may have and discuss the study with study personnel obtaining consent. We estimate
this will take approximately 30 minutes. (iv) The potential participant may take the consent to review, and
contact study personnel to ask further questions or sign it. (v)Participants will be told that involvement in
the study is completely voluntary, and that they can withdraw at any time, for any reason. Research
personnel will also emphasize that any treatment they receive at VAPAHCS will not be affected by their
choice to participate in the study. (vi)n/a
b)
What is the Procedure to assess understanding of the information contained in the consent? How will
the information be provided to participants if they do not understand English or if they have a hearing
impairment? See HRPP Chapter12.2 for guidance.
Participants will be given an explanation of the consent form by trained research staff. In addition, they will
be given ample time to read and review the consent forms and given the opportunity to ask questions or
clarification. Given the nature of the study, individuals must be fluent in English and not have visual or
auditory acuity impairment that would prevent them from completing the assessments, including the
consent.
c)
What steps are you taking to determine that potential participants have the capacity to participate in
the decision-making process? If your study may enroll adults who are unable to consent, describe (i)
how you will assess the capacity to consent, (ii) what provisions will be taken if the participant regains
the capacity to consent,(iii) who will be used as a legally authorized representative, and (iv) what
provisions will be made for the assent of the participant.
The study will not enroll individuals who are not able to give written, informed consent. If there is any
question regarding the potential participant's capacity to give informed consent, they will be screened by the
study PI/PD, who is a licensed clinical psychologist/neuropsychologist for the cognitive competency to
provide written informed consent.
Additional VA questions:
i)
List the people to whom you have formally delegated responsibility to obtain informed consent, and
state whether they have the appropriate training to perform this activity.
Drs. Timothy Durazzo, Claudia Padula, Leanne Williams, Jerome Yesavage, J. Wes Ashford, Ansgar Furst
and study RAs are all delegated responsible staff to obtain written informed consent. All have been trained
in the study, and process for obtaining consent. To-be-hired research personnel will be trained in the consent
processes and completed the required training in Human Subjects, Good Clinical Practice, and HIPAA prior
to obtaining informed consent.
ii)
Will legally effective informed consent be obtained from the participant or the participant's legally
authorized representative (LAR) or both? If LAR, is it clear who can serve as LAR?
No. Individuals who are not able to competently provide independent written informed consent will not be
included in the study.
iii)
Will the circumstances of the consent process minimize the possibility of coercion or undue influence
and provide the prospective participant or their representative sufficient opportunity to consider
whether to participate?
Participants will be given ample time to consider participation in the study and for signing the written
consent form. Participants will also be told that their involvement in the study is completely voluntary, and
that they can withdraw at any time, for any reason. Study personnel obtaining informed consent will also
emphasize that the treatment they receive at the VAPAHCS will not be affected by whether they decline or
participate in the study.
iv)
Will the circumstances of the consent process minimize the possibility of coercion or undue influence?
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 38 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

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Y
Do you certify that the use or disclosure of protected health information involves no more than a
minimal risk to the privacy of individuals?
Y
Do you certify that the research could not practically be conducted with out the waiver?
Y
Do you certify that you have adequate written assurances that the protected health information will
not be reused or disclosed to any other person or entity, except as required by law, for authorized
oversight of the research project, or for other research for which the use or disclosure of protected
health information would be permitted?
Y
Do you certify that the research could not practically be conducted with out access to and use of the
protected health information?
c)
Please describe an adequate plan to protect any identifiers from improper use and disclosure.
All screening documents will be stored in a locked office in a locked file cabinet at the PAVAHCS, building
5 C-441.
d)
Please describe an adequate plan to destroy the identifiers at the earliest opportunity consistent with
conduct of the research, unless there is a health or research justification for retaining the identifiers
or such retention is otherwise required by law.
VA requires screening documents are retained for the 6 years after completion of the study.
16. Attachments
Attachment Name
Attached Date
Attached By
Submitted Date
VA RR&D grant application
08/03/2017
tdurazzo
Seizure protocol
08/03/2017
tdurazzo
TMS_SessionSafety_tcd
08/03/2017
tdurazzo
Alcohol_Abstinence_Self_Eff
icacy_Scale_17 copy
08/03/2017
tdurazzo
Alcohol_Craving_Questionna
ire_Short_Form_Revised_20
08/03/2017
tdurazzo
BAM_Scoring_Clinical_Guid
elines_01-04-2011
08/03/2017
tdurazzo
Barratt Impulsiveness Scale
08/03/2017
tdurazzo
Brief COPE
08/03/2017
tdurazzo
Cannabis Use Disorder ID
Test
08/03/2017
tdurazzo
DSM 5 Alcohol Use Disorder
08/03/2017
tdurazzo
DSM 5 Substance Use
Disorder
08/03/2017
tdurazzo
Early Life Stress
08/03/2017
tdurazzo
Emotion Regulation
Questionnaire
08/03/2017
tdurazzo
Epworth Sleepiness Scale
08/03/2017
tdurazzo
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 40 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Fagerstrom Test for Nicotine
Dependence
08/03/2017
tdurazzo
Insomnia Severity Index
08/03/2017
tdurazzo
NM-ASSIST
08/03/2017
tdurazzo
OCDS
08/03/2017
tdurazzo
WebNeuro Manual
08/03/2017
tdurazzo
WHO Quality of Life
08/03/2017
tdurazzo
MarinaLOS_RRD
08/04/2017
tdurazzo
VA required questions
09/11/2017
tdurazzo
Durazzo_RRD_DMSB_report
_FY1
07/25/2018
tdurazzo
Durazzo_RRD_DMSB_report
_FY2
06/27/2019
tdurazzo
Durazzo_RRD_DMSB_report
_FY3
07/08/2020
lcnguyen
Durazzo_RRD_DMSB_report
_FY4
06/23/2021
mmkaur
CITI training
Certificate_DURAZZO
08/03/2021
mmkaur
Durazzo_RRD_DMSB_report
_FY5
07/07/2022
tdurazzo
DSMB FY6
05/02/2023
tdurazzo
DSMB letter_FY7
04/09/2024
tdurazzo
Obligations
The Protocol Director agrees to:
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Adhere to principles of sound scientific research designed to yield valid results
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Conduct the study according to the protocol approved by the IRB
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Be appropriately qualified to conduct the research and be trained in Human Research protection, ethical
principles, regulations, policies and procedures
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Ensure all Stanford research personnel are adequately trained and supervised
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Ensure that the rights and welfare of participants are protected including privacy and confidentiality of data
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Ensure that, when de-identified materials are obtained for research purposes, no attempt will be made to
re-identify them.
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Disclose to the appropriate entities any potential conflict of interest
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Report promptly any new information, modification, or unanticipated problems that raise risks to
participants or others
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 41 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

•
Apply relevant professional standards.
Any change in the research protocol must be submitted to the IRB for review prior to the implementation of
such change. Any complications in participants or evidence of increase in the original estimate of risk should
be reported at once to the IRB before continuing with the project. Inasmuch as the Institutional Review
Board (IRB) includes faculty, staff, legal counsel, public members, and students, protocols should be written
in language that can be understood by all Panel members. The investigators must inform the participants of
any significant new knowledge obtained during the course of the research.
IRB approval of any project is for a maximum period of one year. For continuing projects and activities, it is
the responsibility of the investigator(s) to resubmit the project to the IRB for review and re-approval prior to
the end of the approval period. A Notice to Renew Protocol is sent to the Protocol Director 7 weeks prior to
the expiration date of the protocol.
https://stanfordmedicine.box.com/shared/static/qbsi8u8h47qsotxhdpuzz50xlrqa0sgo.pdf Report promptly any
new information, complaints, possibly serious and/or continuing noncompliance, or unanticipated problems
involving risks to participants or others.
All data including signed consent form documents must be retained for a minimum of three years past the
completion of the research. Additional requirements may be imposed by your funding agency, your
department, or other entities. (Policy on Retention of and Access to Research Data, Research Policy
Handbook,
http://doresearch.stanford.edu/policies/research-policy-handbook/conduct-research/retention-and-access-research-data)
APPROVAL LETTER/NOTICE NOTE: List all items (verbatim) that you want to be included in your
approval letter (e.g., Amendment date, Investigator's Brochure version, consent form(s) version(s),
advertisement name, etc.) in the box below.
Y
By checking this box, I verify that I, as the Protocol Director (PD) responsible for this research protocol,
have read and agree to abide by the above obligations, or that I have been delegated authority by the PD to
certify that the PD has read and agrees to abide by the above obligations.
Protocol # 42600 ( Continuing Review )
PROTOCOL
PD: Timothy Durazzo
APPLICATION FORM
Page 42 of 42
Review Type: Regular
Human Subjects Research
Medical
Stanford University
Title :
Transcranial Magnetic Stimulation for the Treatment of Veterans With Alcohol Use Disorders
Approval Period:
02/28/2025 - 02/28/2026

Data Analyses  
Primary Hypothesis:  
1a) Veterans who receive active rTMS treatment for AUD demonstrate a significantly lower frequency of 
relapse at 6 months following treatment than controls (i.e., Veterans with AUD who receive sham rTMS).  
Statistical Approach: Primary Hypothesis 1a will be tested with binary logistic regression. The 
criterion/dependent measure is relapse status (abstained or relapsed during the 6 months after last rTMS 
session). Treatment group (active rTMS vs. control) is the target predictor, and covariates will include age and 
composite neurocognitive functioning (based on demographically adjusted RBANS total score) as these 
variables may account for both within and between subject group variance [89, 91]. PTSD severity (based on 
PCL-5 total score), substance use severity (based on NIDA Drug Survey composite score), depression severity 
(based on BDI total score), and/or smoking severity (based on pack-years) will be considered as covariates if, 
after random assignment, there are post-hoc differences between treatment groups on these variables 
following breaking of the blind. 
1b) Veterans who receive active rTMS treatment for AUD will demonstrate a significantly greater duration of 
abstinence in the 6 months following treatment than controls.  
Statistical Approach: Primary Hypothesis 1b will be tested with Cox regression. The criterion/dependent 
measure is duration of abstinence after final rTMS session, and covariates include those listed for Primary 
Hypothesis 1a. 
Secondary Hypothesis:  
In the active rTMS group, Veterans with: (a) lower Glx concentration, (b) lower perfusion (blood flow), and (c) 
smaller volume of the left DLPFC at baseline will demonstrate a longer duration of abstinence over 6 months 
post treatment. Confirmation of this hypothesis will indicate that participants who exhibit lower baseline Glx 
concentration, lower perfusion (blood flow), and/or smaller left DLPFC volume, and receive active rTMS, 
demonstrate the most robust rTMS treatment response because rTMS addresses these key neurobiological 
deficits that are associated with increased relapse risk. Confirmation of this hypothesis will advance our 
understanding of the neurobiological characteristics that predict the greatest benefit from rTMS at entry into 
treatment for AUD. 
Statistical Approach: The Secondary Hypothesis will be tested with generalized linear mixed modeling or linear 
mixed modeling, depending on the distribution of the dependent measure. Duration of abstinence is the 
dependent measure. Neuroimaging measure (e.g., Glx level) and treatment group (active rTMS vs. control) are 
the target predictors, with age as a covariate because it will likely account for significant within and between 
subject variance [20]. Smoking, PTSD and/or substance use severities will be used as covariates if there are 
post-hoc differences between treatment groups on these variables after random assignment. We predict an 
interaction between the specific neuroimaging measure (e.g., Glx level) and treatment group; follow-up simple 
effect tests will indicate that participants in the active rTMS group with lower Glx concentration, lower perfusion 
(blood flow), and smaller volume of the left DLPFC at baseline will show the longest duration of abstinence. 
Separate models will be run for each neuroimaging predictor to minimize the risk of overfitting and 
corresponding inflated Type I error. To control significance levels of main effects and interactions for multiplicity 
of tests, we will employ a modified Bonferroni procedure described in our previous studies (see [71] for details). 
Exploratory Hypothesis 1  
1a) Veterans with co-occurring MDD, who receive active rTMS, demonstrate a significantly lower frequency of 
relapse over 6 months following treatment than controls (i.e. Veterans with co-occurring MDD who receive 
sham rTMS).  
Statistical Approach: Exploratory Hypothesis 1a will be tested with binary logistic regression. The 
criterion/dependent measure is relapse status (abstained or relapsed during the 6 months after last rTMS 
session). Treatment group (active rTMS vs. control) is the target predictor, with antidepressant use (binary, 
yes/no) as a covariate. Education and severity of PTSD, substance use, and/or depressive symptomatology 
will be considered as covariates if, after random assignment, there are post-hoc differences between treatment 
groups on these variables following breaking of the blind. 
1b) Veterans with co-occurring MDD, who receive active rTMS, demonstrate significantly greater duration of 
abstinence in the 6 months following treatment than controls. 
Statistical Approach: Exploratory Hypothesis 1b will be tested with Cox regression. The criterion/dependent 
measure is duration of abstinence after the final rTMS session. The target predictor and covariates include 
those for Exploratory Hypothesis 1a. 

Exploratory Hypothesis 2  
2a) Cigarette smokers, who receive active rTMS, demonstrate a significantly lower frequency of relapse over 6 
months following treatment than controls (i.e., Veterans with co-occurring smoking who receive sham rTMS).  
Statistical Approach: Exploratory Hypothesis 2a will be tested with binary logistic regression. The 
criterion/dependent measure is relapse status (abstained or relapsed during the 6 months after last rTMS 
session). Treatment group (active rTMS vs. control) is the target predictor and with current pharmacotherapy 
for smoking cessation use (binary, yes/no) as a covariate. Education and severity of PTSD, substance use, 
and/or smoking severity (based on pack-years) will be considered as covariates if, after random assignment, 
there are post-hoc differences between treatment groups on these variables following breaking of the blind. 
2b) Smokers, who receive active rTMS, demonstrate a significantly greater duration of abstinence over the 6 
months following psychosocial treatment than controls. 
Statistical Approach: Exploratory Hypothesis 2b will be tested with Cox regression. The criterion/dependent 
measure is duration of abstinence after final rTMS session. Treatment group is the target predictor and 
covariates include those for Exploratory Hypothesis 2a. 
Tertiary Analyses  
We will concurrently examine the associations between treatment group, multiple neurobiological, 
neurocognitive and clinical variables (and their potential interactions) and relapse status via an advanced 
multivariate dynamic longitudinal latent variable modeling framework [23]. However, we are mindful of the 
proposed sample size and will avoid building models that risk overparameterization and overfitting.