Identification of Thermogenic Silencing Regulatory Factors as Biomarkers of Metabolic Health in Humans
Phase: NA
Conditions: Obesity, Metabolic Disease, Cold Exposure
Sponsor: Rockefeller University

Institutional Review Board
Sarah J. Schlesinger, MD Chair
Dale Miller, BA CIP
Sr. IRB Specialist (212) 327-8411
Vanessa Smith, MPS, CIP, CIM
Sr. IRB Specialist (212) 327-8410
Hospital Bldg., Rm 201 Box 331
April 15, 2024
 
Paul Cohen, MD, PhD
RUH - Laboratory of Molecular Metabolism (Paul Cohen)
The Rockefeller University
 
RE:PCO-1051 Identification of thermogenic silencing regulatory factors as biomarkers of metabolic health in 
humans
Dear Dr. Cohen,
Thank you for submitting the modifications to documents for the above protocol (iRIS submission # 
375150), as requested in our letter of February 1, 2024.  On behalf of the Board, I have reviewed and approved the 
modifications. 
Having met all of the criteria for approval outlined in 45 CFR 46.111 and 21 CFR 56.111, this study was 
reviewed and granted stipulated approval at the convened meeting of the Institutional Review Board (IRB) 
on February 1, 2024.  The final approval period is April 15, 2024 through April 14, 2025. 
The following documents were reviewed: 
Type
Document Name
Version
Date Submitted into 
Workflow
Submission Response by Board:
Institutional Review Board 
Review Response Submission 
Form  
Version 
1.0 
04/15/2024
02:49 PM EDT  
Review Response Submission 
Form  
Version 
1.0 
  
Submission Form:
Submission Form 
Initial Review Submission Form  Version 
1.1 
04/15/2024
02:49 PM EDT  
Submission Form 
Initial Review Submission Form  Version 
1.0 
  
Submission Attachments:
Application 
Study Application  
Version 
1.1 
04/15/2024
02:49 PM EDT  
Application 
Study Application  
Version 
1.0 
01/23/2024
03:39 PM EST  
Consent (English)
Barrow/Cohen ICF 11April2024 Version 
1.2
04/15/2024
02:49 PM EDT  
Consent
Barrow/Cohen ICF 1/24 
Version 
1.0 
01/23/2024
03:39 PM EST  
Document -
Text for Advertisements
Advertisement Flyer Polar Bear Version 
1.0
04/15/2024
02:49 PM EDT 

Institutional Review Board
Sarah J. Schlesinger, MD Chair
Dale Miller, BA CIP
Sr. IRB Specialist (212) 327-8411
Vanessa Smith, MPS, CIP, CIM
Sr. IRB Specialist (212) 327-8410
Hospital Bldg., Rm 201 Box 331
Type
Document Name
Version
Date Submitted into 
Workflow
Document -
Text for Advertisements
Advertisement Flyer Hands 
Version 
1.0
04/15/2024
02:49 PM EDT 
Document -
CCTS Utilization Report
CCTS Utilization Report 
Version 
1.0
04/15/2024
02:49 PM EDT 
Document -
Study Questionnaire
IPAQ Phone Questionnaire 
Version 
1.0
04/15/2024
02:49 PM EDT 
Document -
Study Questionnaire
DHQ3 Serving Size 
Questionnaire 
Version 
1.0
04/15/2024
02:49 PM EDT 
Document -
Schedule of Events
SOE 1/2024 
Version 
1.0
01/23/2024
03:39 PM EST 
Document -
Other Supporting Documentation
IRB Infographics 
Version 
1.0
01/23/2024
03:39 PM EST 
Document -
Other Supporting Documentation
Prescreening Survey 
Version 
1.0
01/23/2024
03:39 PM EST 
Document -
Other Supporting Documentation
Punch Biopsy SOP 
Version 
1.0
01/23/2024
03:39 PM EST 
Document -
CCTS Utilization Report
CCTS Utilization Report 
10April2024 
Version 
1.1
04/15/2024
02:49 PM EDT 
Document -
CCTS Utilization Report
CCTS Utilization Report 1/24 
Version 
1.0
01/23/2024
03:39 PM EST 
Document -
Text for Advertisements
Advertisement Flyer 
Version 
1.1
04/15/2024
02:49 PM EDT 
Document -
Text for Advertisements
Advertisement Flyer 
Version 
1.0
01/23/2024
03:39 PM EST 
Document -
HIPAA Authorization form
HIPAA Form 
Version 
1.1
04/15/2024
02:49 PM EDT 
Document -
HIPAA Authorization form
HIPAA Form 
Version 
1.0
01/23/2024
03:39 PM EST 
The number assigned to this protocol is PCO-1051.
Please note that submission for Continuing Review of this protocol is due no later than 9:30 
am on February 25, 2025.
It is the Principal Investigator’s responsibility, as required by Federal regulations, to (1) Submit any 
proposed changes in approved studies to the IRB for review and approval prior to initiation, except where necessary 
to eliminate apparent immediate hazards to the subjects; (2) To promptly inform the IRB, appropriate institutional 
officials, the Office for Human Research Protections (OHRP) and the FDA, if applicable of any unanticipated 
problems involving risks to subjects or others and research related injuries; (3) To obtain the informed consent of the 
participant in the manner and format approved; and (4) To resubmit to the IRB for continuing review at the interval 
determined by the IRB to be appropriate to the risk, but not less than once a year.
 
Sincerely yours,
 

Institutional Review Board
Sarah J. Schlesinger, MD Chair
Dale Miller, BA CIP
Sr. IRB Specialist (212) 327-8411
Vanessa Smith, MPS, CIP, CIM
Sr. IRB Specialist (212) 327-8410
Hospital Bldg., Rm 201 Box 331
Signature applied by Sarah J Schlesinger  on 04/15/2024 06:45:38 PM EDT
 
Sarah J. Schlesinger, MD
Chair, Institutional Review Board
The Rockefeller University
Federal Wide Assurance # 000004658
 

    Study Application (Version 1.2)
1.0
General Information
*Please enter the full title of your study::
Identification of thermogenic silencing regulatory factors as biomarkers of metabolic health in humans
 
 
*Please enter the study short title:
Thermogenic Silencer Regulatory Factors in Humans
* This field allows you to enter an abbreviated version of the Study Title to quickly identify this study.
 
 
Is this Study using Subject Management?
Yes
No
 
 
2.0
Add departments
2.1 List departments associated with this study:
Is
Primary? Department Name
RUH - Clinical Research Support Office (CRSO)
RUH - Laboratory of Molecular Metabolism (Paul Cohen)
RUH - Rockefeller University Hospital (RUH)
 
3.0
Assign key study personnel(KSP) access to the study
3.1 * Please add a Principal Investigator for the study:
Name
Role
Training Record
Cohen, Paul, MD, PhD
Principal Investigator
 View Training Record
3.2 If applicable, please select the Research Staff personnel:
A) Additional Investigators
Name
Role
Training Record
Barrow, Joeva, PhD
Clinical- Co-Investigator
 View Training Record
Gomez Banoy, Nicolas, MD
Clinical- Co-Investigator
 View Training Record
Walker, Jeanne Marie, DNP, ANP-BC
Clinical- Co-Investigator
 View Training Record
B) Research Support Staff
Name
Role
Training Record
Li, Muying, MS
Research Assistant
 View Training Record
Rauso, Anna, BS
Facilitator
 View Training Record
Ronning, Andrea, M.A.
Bionutritionist
 View Training Record
3.3 *Please add a Study Contact:
Name
Role
Training Record
Barrow, Joeva, PhD
Study Contact
 View Training Record
Cohen, Paul, MD, PhD
Study Contact
 View Training Record
Li, Muying, MS
Study Contact
 View Training Record
Rauso, Anna, BS
Study Contact
 View Training Record

3.0
Assign key study personnel(KSP) access to the study
Walker, Jeanne Marie, DNP, ANP-BC
Study Contact
 View Training Record
The Study Contact(s) will receive all important system notifications along with the Principal Investigator. (e.g. The project contact(s) are
typically either the Study Coordinator or the Principal Investigator themselves).
4.0
Rockefeller University Conflict of Interest
4.1   Investigator Financial Conflict of Interest All KSP must complete an annual certification of their Significant Financial
Interest (“SFI”) disclosures in the University’s online Research Administration System at
https://RAS.rockefeller.edu.  Disclosures also must be updated in connection with new human subjects research
protocols (“Research Certification”), and within 30 days of discovering or acquiring a new SFI.  To avoid delays in the
IRB review process, when prompted by an email from rascoi@rockefeller.edu requesting an updated Research
Certification, KSP should click on the Research Certification link contained in that email notification, or go to
https://RAS.rockefeller.edu, to (a) review and update his or her SFI disclosures or certify that he/she has no
updates, as appropriate, and (b) indicate whether any of his/her SFI disclosures are reasonably related to the design,
conduct, or reporting of the research protocol. If a KSP discloses a SFI that might constitute a conflict of interest with
respect to the proposed protocol, he or she must e-mail a copy of the Lay Summary of the draft protocol to Teresa
Solomon, Esq. (solomot@rockefeller.edu).  Doing so will facilitate addressing COI issues in step with the development
of the study protocol.  Non-compliance or tardiness in making or updating COI disclosures will result in a delay in IRB
review.      Institutional Conflict of Interest:
 
As early as possible the PI (or a designee) preparing a clinical research protocol must review a list of entities in which
The Rockefeller University has an Institutional Financial Interest at https://icoi.rockefeller.edu/account/login.php.  If
the proposed study involves any entity on that list, the PI (or designee) must notify Teresa Solomon, staff to the FCOI
Committee, by e-mail solomot@rockefeller.edu and Sarah Schlesinger, Chair of the IRB, by email:
schless@rockefeller.edu, provide the name(s) of the entities and a copy of the Lay Summary. Doing so will facilitate
addressing institutional COI issues in step with the development of the study protocol. Failure to take steps to review
and address potential institutional conflicts of interest will delay the IRB review process.  
5.0
External Personnel
5.1   List external personnel who will be working on the study:
Name
Institution
Telephone
E-mail
Role
Joeva Barrow 
Cornell University 
352-575-7051 
jbarrow@rockefeller.edu Clinical- Co-
Investigator
Muying Li 
Cornell University 
917-593-9655 
MLi02@rockefeller.edu
Research Assistant
6.0
Delegation of Authority 
6.1   Enter authorized activities for all Rockefeller University personnel named on the study. 
Activity Codes:
1.   Informed consent **
11.  Participant recruitment
21.  Skin biopsy *
2.   Inclusion / exclusion criteria
12.  Perform assays 
22.  Conduct sleep study
3.   Medical/medication history *
13.  Specimen / sample analysis
23.  Diet design and preparation
4.   Perform Physical Exam *
4a. Write / Sign LIP orders *    
14.  Lumbar puncture *
24.  Nutritional assessment and counseling
5.   Skin assessments and photos
15.  Femoral line placement *
25.  Addition of PABA to food 
6.   Study drug dispensing *
16.  Central line placement * 
26.  Data analysis
7.   Study drug administration *
17.  Insulin clamp procedure *
27.  Data review
8.   Study drug reconciliation
18.  Leukapheresis *
28.  Data management 
9.   Study drug compliance
19.  Sigmoidoscopy * 
29.  Maintain regulatory documents / files
10. Administer study questionnaire(s)
20.  Fat biopsy *
30.  Complete CRF's
Add up to three additional authorized activities specific to this study (do NOT add activities that
have previously designated codes):
31:
Apply Cooling Vest
32:
Hip and Waist Measurement
33:
Punch Biopsy
 Activity Codes Continued:
34.  Behavioral Testing
35.  Bod Pod
36.  Bone Marrow Aspiration *
37.  Neuropsychological Testing *
38.  Conduct Focus Group 
39.  Conduct Smell Study
40.  Genetic Counseling *
41.  Apply EEG Electrodes **
42.  Olfactometer Test
43.  Study Participant Teaching
44.  Resting Energy Expenditure 

45.  Source Document Review & Correction 
46.  Medical Photography
47.  See 4a 
48.  Adverse Event Assessment
49.  Clinical Trial Registration 
50.  Study Support Drug Dispensary
51.  Internal Monitoring 
52.  Randomization 
Enter delegation of authority for Rockefeller University Key Study Personnel:
NOTE:
*     Indicates procedures requiring the individual complete specific credentialing BEFORE the activity may be
added to their delegated activities.
**  Indicates procedures requiring the individual complete specific training BEFORE the activity may be added
to their delegated activities.
Name
Title
Authorized Activities
Start Date
End Date
Cohen,
Paul, MD,
PhD
PI
4a,26,27,51
01/12/2024
Barrow,
Joeva, PhD
Co-I
1,2,10,13,26,27,28,30,31,45,49,51
01/12/2024
Li, Muying,
MS
Rsch
Technician
1,2,10,13,26,27,28,29,30,31,45,48,51
01/12/2024
Ronning,
Andrea,
M.A.
Bionutritionist
32,35
01/12/2024
Walker,
Jeanne
Marie, DNP,
ANP-BC
Co-I
1,2,3,4,4a,10,33,48
01/12/2024
Rauso,
Anna, BS
Facilitator
1,29
01/12/2024
Enter delegation of authority for additional Rockefeller University Key Study Personnel:
Name
Title
Authorized Activities Start Date
End Date
No results found
Enter the authorized activities for External Personnel:
Name
Title
Authorized Activities Start Date
End Date
No results found
7.0
Study Description
7.1  
Study Classification
Full Review
7.2  
* Submission Request Category

Note: For each submission, please designate the level of review, or “Submission Request Category” you are
requesting. When completing this field, please indicate the level of review you are requesting for the specific
submission you are working on.
For example, if you are submitting an Expedited Amendment request to change the Key Study Personnel on your
existing Full Board study, you should select “Expedited Review” in both the Amendment Submission Form and Study
Application. The IRB will confirm an Expedited review of the Amendment submission is appropriate, and the overall
study will remain classified as a full Board review. Please see the help bubble for guidance.
To submit a request for a Not Human Subjects research determination, please exit this form and select the
“Not Human Subjects Research Determination” form under Create a New Study.
Exempt from Review 
Exempt with Limited Review 
Expedited Review 
Full Review 
7.3   * Lay Summary
Please provide a summary of your study in lay language that is easily understood by a non-scientist. The summary
should be no more than half a page (500 words or less) and should contain a clear statement of the rational for the
study.
Please click on the help bubble to get the information on " How to use iRIS text editor."
Please provide a summary of your study in lay language.  The summary should be no more than a half
page (500 words or less) and should contain a clear statement of the rationale for the study. 
A promising approach to correct the metabolic dysfunction associated with obesity is to activate brown fat non-
shivering thermogenesis (NST). A critical limitation with NST as a therapeutic option, however, is that this
beneficial process is silenced under human physiological temperature conditions and the mechanisms of how this
occurs is unknown. This study will be the first to identify human NST silencing factors that may be targeted for
the treatment of obesity and metabolic disorders.
7.4  
* Public Health Impact Statement
Provide a brief plain language statement (100 words or less) of the value of the research proposed and
its potential impact on population health. Additional instructions located in Help.
 
Why- Obesity and its associated health risks are the leading causes of preventable death worldwide. It may be
possible to fight obesity by activating human brown fat- a type of fat associated with heath --but the tissue is
silenced (not metabolically active) for most of human life. Cold exposure can turn on brown fat, but the
mechanisms controlling its silencing are unknown.
What- We will define the factors that control whether brown fat is active or silenced by studying the proteins and
other chemicals released into the blood of volunteers subjected to the kind of cold-exposure that stimulates
brown fat. 
How- Understanding how to control the activation of healthy brown fat could provide insights into the design of
new therapeutic approaches to combat or prevent obesity and type 2 diabetes.  
8.0
Clinical Trial Registration
8.1  
Clinical Trial Registration
The types of studies listed below must be registered at Clinical Trials website before enrolling the
first participant in order to be in compliance with federal regulations and preserve the opportunity to
publish the study in journals that adhere to the ICMJE guidelines. Please check the answer that best
applies.
Study involves testing of FDA regulated drugs or biologics (See HELP) 
Study is funded by the NIH, and meets the definition of a “clinical trial” (see HELP) 
Study meets the ICMJE definition of a “clinical trial” (See HELP) 
Additional funding agency or journal requires clinical trial registration 
None of the above 
If you selected 1, 2, 3, or 4 you must register your trial with ClinicalTrials.gov through the Rockefeller
University institutional account. Please contact the Clinical Research Support Office x7408 for
assistance.
9.0
Study Overview/Summary

9.1   * Who initiated this study?
Please specify one:
Principal Investigator Initiated 
Industry Initiated 
Other 
9.2   *Are other institutions involved in the study?
No 
Yes 
Please enter the name and IRB approval details for each involved institution. Include a description of
each site’s involvement in the Methods and Procedures section.
Attach external IRB approval letters in Other Study Documents.
Name of Other
Institution
Date of IRB
Approval by
Other Institution
Date of Pending
Approval by
Other Institution
Date of IRB
Expiration at
Other Institution
Date of
Exemption at
Other Institution
Check if Other
Institution is
relying site in a
Single IRB
arrangement
Cornell
University
06/03/2024
9.3   * Is this a multi-site trial using a single IRB (sIRB) review arrangement? Please see help bubble for definition.
  Yes  
  No
9.4  
* Who (What) is to be studied?
Human Subjects - including coded samples and/or data with links to Identifiers
Deidentified Samples - unable to be linked to identifiers by receiver
Data Only - unable to be linked to identifiers
Identifiable samples or data for exemptions (per 104 (s)(4))
9.5   *Study Type:
Interventional 
Observational 
9.6   The initial date of IRB approval/determination was:
04/15/2024
9.7   * What is the expected duration of the study?
Two years
9.8   * Are any of the following agents to be used in the study?
Check all that apply:
FDA Approved Drug
FDA Approved Drug for Off-Label Purpose (This might require an IND)
Investigational New Drug
Biologic Agents
Nutritional Supplements
Placebo
Vaccines
No Agents
FDA Exemption to use Study Drug
9.9   * Are investigational devices to be used in the study?
  Yes  
  No
9.15   Special Research Procedures

Does the study propose to directly involve participants in the following special research procedures?
Recombinant DNA
Gene Therapy
Fetal Tissue
Embryonic Stem Cells
Induced Pluripotent Stem Cells
CRISPR-Cas9
If any item is checked, please see Help for details.
9.16   * Radioactive Isotopes Involved
Will participants be exposed to any radiation other than routine x-rays solely for clinical care
purposes? 
  Yes  
  No
 
10.0
Interventional
10.1   *Interventional, please specify:
Open Label 
Single Blind 
Double Blind 
Other 
11.0
Study Phase:
11.1   Study Phase:
Select where applicable
Phase 0 
Phase I 
Phase I/II 
Phase II 
Phase III 
Phase IA 
Phase IB 
Phase IIA 
Phase IIB 
Phase IB/IIA 
Phase IIB/IIIA 
Phase IIIA 
Phase IIIB 
N/A 
12.0
Objectives and Rationale
12.1   * Overview
Briefly state the purpose of this study. Give enough background and rationale to provide both
scientists and lay members of the IRB and ACCTS with the basis for exposing human participants to
the risks involved.
Obesity and associated metabolic disease such as type 2 diabetes continue to be one of the leading causes of
death worldwide, demanding additional research into novel treatments beyond our current options. One
promising experimental approach to overcome the metabolic dysfunctions associated with obesity, such as
insulin resistance and glucose imbalance, is to activate brown fat non-shivering thermogenesis (NST). Activated
human brown fat increases energy expenditure at a molecular level and is associated with both improved insulin
tolerance and glucose homeostasis. A critical limitation with human brown fat as a therapeutic option, however,
is that its beneficial metabolic potential is restricted in a silenced state under physiological temperature
conditions for most of human life. The regulatory factors that govern this silencing process are completely
unknown. While many groups continue to seek novel mechanisms to activate brown fat, we present a unique
approach, aiming to decipher the mechanisms that govern human brown fat silencing. We hypothesize that if we
can define the regulatory factors that silence brown fat NST, then these factors can be targeted for ablation to
eliminate the “off switch”, thereby keeping brown fat in a constitutively active state. Identification of human NST
silencing factors will be critical to unlock the metabolic benefits of human brown fat and would represent
promising treatment opportunities for type 2 diabetes and other obesity-related disorders. We have identified a
suite of silencing factors in mice and given our strong proof-of-concept studies, we anticipate that the BAT
silencing regulatory program will also play a critical role in humans. We also anticipate that these BAT silencing
regulatory factors will be differentially expressed both in lean vs obese individuals and between individuals with

and without type 2 diabetes. Understanding these relationships will allow for precision treatment opportunities
for type 2 diabetes in the future.
The overall goal of this proposal is to unlock the metabolic benefits of human brown fat by defining the
regulatory mechanisms that keeps BAT in a silenced state. We will generate the first human secretome and
transcriptome compendium from human plasma and subcutaneous adipose tissue respectively which will be
composed of target proteins, metabolites, and genes that are differentially expressed in response to NST
silencing conditions. Top candidates from our profiling will then be functionally validated in human adipocytes for
their role in NST silencing. Our work will be an important resource for the field and will identify novel candidates
that may harbor regulatory potential to govern the NST silencing process in humans. These factors can then be
targeted to promote the constitutive activation of NST in order to overcome the metabolic dysfunction
associated with obesity and metabolic disease. Given the invasive nature of direct human brown fat sampling,
we will instead interrogate circulating factors in human plasma as a proxy for metabolic health. Indeed, many
groups such as Bruce Spiegelman, Camilla Scheele, and many others have reported secreted circulating factors
derived from human brown fat termed “BATokines”. We hypothesize that if these circulating factors are present
in the NST active stage, then NST silencing factors may also be present in circulation during the silenced state.
In addition, we will also obtain subcutaneous adipose tissue for RNA profiling to identify genes that are
upregulated under NST silenced conditions compared to cold exposure. 
12.4   * Engaging Stakeholders: Describe any plans to engage other stakeholders (Scientists, practitioners, patients,
advocacy groups, etc.) for hypothesis generation, or feasibility purposes.  
Input for this study was obtained from Dr. Carol Haft, PhD. who is a program director in the Division of Diabetes,
Endocrinology, and Metabolic Diseases (NIDDK) at the NIH.
12.5   * Hypothesis
Describe the research hypothesis in a single sentence.
We hypothesize that the NST silencing regulatory factors that we identified in mice, also exist in humans and are
differentially expressed in lean vs obese human subjects and in individuals with and without Type 2 diabetes.
12.6   * Aim(s)
Indicate how you will address the hypothesis (e.g., to compare groups, to estimate a parameter, to
ascertain feasibility). Since the sample size determination is usually based on the primary aim only,
the primary aim should be sufficient to justify the study.
Aim 1. Define the human secretome under NST silencing conditions, in lean and obese health volunteers, and
individuals with type II diabetes, who are undergoing controlled cold-exposure and rewarming to induce and
resilience brown adipose tissue activation.
Aim 2. Define the human adipose tissue transcriptome in response to NST silencing conditions to
identify novel genes that can be targeted for the treatment of obesity and metabolic disorders.
12.7   * Primary Outcome(s)
Indicate which variable(s) will be assessed to judge the primary specific aim.  Give measurement
units, if applicable.
Generation of transcriptomic, proteomic, and metabolomic datasets of human candidate genes, proteins, and
metabolites. 
12.8   * Secondary Outcome(s)
Indicate which additional variable(s) will be assessed to judge the secondary outcome(s). Give
measurement units, if applicable.
 
Nutritional and anthropometric assessments of individuals correlated to expression patterns of human NST
silencer regulatory factors.
Association of individual nutritional and anthropometric assessments to expression pattenrs of Human NST
silencer regulatory factors. 
12.9   * Methods and Procedures
Please provide a description of the laboratory and clinical analyses and procedures that will be
performed. Include the role of external collaborators and consultants when appropriate. Please refer to
Help text for Guidance.
Remote Pre-Visit and Consenting
1. The recruitment team at the Rockefeller University (RU) will recruit individuals from the RU Research
Participant Repository (RKO-0648) who meet the eligibility criteria for the study (age, BMI). The recruitment
team will direct participants to complete an electronic pre-screening survey through REDCap to further gauge
eligibility criteria (i.e diabetes status and management). 
2. The recruitment team will then refer eligible participants who have passed the pre-screening metric to the
Barrow-Cohen research team who will then provide participants with the informed consent document via email
through REDCap according to RU Telephone/eConsent SOP for review.
3. The Barrow-Cohen research team will then schedule a Zoom conversation to review a 1-page infographic
containing the study design and researchers will answer any questions participants may have. After the protocol
is fully described, if the individual wants to enroll, they will be guided through eConsent process by the Barrow-
Cohen research team. Participants will be asked to provide consent by signing the eConsent via REDCap

according to the established RU eConsent SOP and will be enrolled in the study. A suitable date for in-person on-
site Visit #1 will be established at the end of the Zoom meeting. 
Requirements prior to VIST #1.
All subjects will be required to fast overnight for 12 hrs prior to the site visit (21:00 – 09:00, study will
commence at 09:00 +/- 1 hour) and refrain from caffeine and excessive exercise (i.e. vigorous aerobic exercise,
such as running or gym workout sufficient to increase the heart rate and perspiration) for 12 hours prior to the
visit. 
VISIT #1 (On-Site)
This meeting will take place at the Rockefeller University Hospital and will take approximately 2-3 hours. During
this meeting, we will 
Obtain anthropometrics measurements in a metric system from the participants including the weight and
height to calculate Body Mass Index (BMI). 
Body fat and muscle composition will also be assessed via Bod Pod following Rockefeller’s standard
operating procedures. 
Clinical staff will then obtain blood (35mL) for basic clinical labs (glucose, A1C, TSH, T3, T4 etc). 
Female subjects will complete a point-of-care urine pregnancy and will be asked to provide information
about their menstrual cycle. 
Following these assessments, 
A breakfast meal prepared by the Rockefeller Bionutrition metabolic kitchen will be provided to the
participants. 
Participants will then engage in comprehensive nutrition and anthropometric assessments. Participants
will first fill out the Diet History Questionnaire III (DHQ III) by the National Cancer Institute online
(https://epi.grants.cancer.gov/dhq3) to obtain diet quality and patterns information under the
supervision of research staff.  
Research staff will then conduct a structured interview of the International Physical Activity Questionnaire
(IPAQ) to evaluate participant’s physical activity level. 
Following the nutrition assessments, the Barrow research group will calculate estimated energy
requirements (EER) and nutrition requirements using the gold standard EER equations developed by the
National Academies of Sciences, Engineering, and Medicine Dietary Reference Intakes for Energy (DRI)
2023 for individuals. 
The Barrow research team will then formulate an individualized tailored nutrition beverage that will meet 33% of
each participants’ daily EER. This nutrition beverage (Katefarm Nutrition Shake which is USDA Organic, Non-
GMO, plant-based, vegan, and does not contain milk, eggs, fish, shellfish, tree nuts, peanuts, wheat, or
soybeans https://shop.katefarms.com/products/nutrition-shake) will be provided to participants on Visit
#2 to ensure that study participants are maintained at nutrient baseline and maintained in a fed state
throughout the study. The formula will be provided to Rockefeller Bionutrition department, by the Barrow
research team, for storage, preparation and administration. A suitable date for Visit #2 (experiment date) will
be established at the end of Visit 1. 
Requirements Prior to VISIT #2
All subjects will be required to have a hearty meal of choice the night before the visit and fast overnight for 12
hrs prior to the visit (21:00 – 09:00, study to begin at 09:00 +/- 1 hour) and refrain from caffeine and
excessive exercise (i.e. vigorous aerobic exercise, such as running or gym workout sufficient to increase the
heart rate and perspiration) for 12 hours prior to the visit. 
NOTE: Based on data from laboratory animals, exercise is linked with brown fat activation, thus refraining from
exercise immediately prior to the experiment will minimize potential variability in BAT activation between all
participants. 
VISIT #2 (On-Site)
Participants will engage in a 6.5-hour study that will encompass a customized cold environmental exposure, and
subsequently a thermoneutral exposure period. The time length for cold and rewarming periods were selected
based on previous research by Aaron Cypess and others in the field.  There will be five blood collections of 16mL
each for a total of 80mL over a span of 6.5 hours and two punch biopsies obtained after cold and warm
environmental exposure that will be cryopreserved for transcriptomic analysis. The total volume of blood
sampling (80 mL) is in accordance with the American Red Cross safety guidelines.
Baseline (30min). Participants will arrive to the Rockefeller University Hospital at 9am and enter a patient room
kept at room temperature conditions (25oC). They will be instructed to de-robe in private quarters and don
hospital gowns and the first of five blood draws of 16mL will be collected into both EDTA-treated and non-
treated tubes (8mL each) and stored at 4oC for later plasma and serum processing respectfully for proteomic
and metabolomics analysis.  After this, the Bionutrition department will measure the individualized tailored
chilled complete liquid nutrition meal replacement beverage (Katefarms Nutrition Beverage) at the amount
provided by the Barrow research team to meet a third of participants’ dietary reference intakes (DRI) for energy
based on their individualized EER that was calculated in Visit #1. This formula will then be administered to each
research participant. Bionutrition will mark the order as complete, in Cerner, once it is provided to the research
participant.  This will represent “breakfast” and ensure that all participants begin the cold exposure study at
nutrient baseline to remove any confounding effects from diet or fasting. The second blood sampling will then

take place 30min following feeding. Throughout the study, participants will be regularly offered water to ensure
that they are properly hydrated.
Cold 
Exposure 
(3 
hours). 
Water-perfused 
cold 
vests
(https://www.polarproducts.com/polarshop/pc/CoolOR-13-Quart-System-with-Arctic- 
Chiller-
p24757.htm) will be placed over the hospital gowns on study participants. The cold vests are connected to an
automated water-cooling artic chiller reservoir that delivers continual cool water infusions to the vest to
maintain a constant cold temperature. The Cohen lab has vests of varying sizes (S, M, L, XL, XXL) to
comfortably fit all study participants. We will employ the established adaptive cooling method where the cooling
temperature is set to 2oC above an individual’s shivering threshold. This will ensure that muscle thermogenesis
is not being engaged to maximize the activation of brown fat non-shivering thermogenesis. The starting infusion
temperature will be set to 16oC and the Barrow and Cohen research teams as well as the Rockefeller hospital
staff will monitor for signs of shivering using a combination of direct observation and participant reporting. When
shivering occurs, the temperature setpoint on the cold vest will be raised by increments of 2oC until shivering
subsides which will be the defined cooling temperature for that individual throughout the study period. If
shivering does not occur withing a 10 min period, then the temperature will be lowered by increments of 2oC
until shivering begins, at which the setpoint will be increased by +2oC. Participants will be cold exposed for a
period of 3 hours as has previously been shown to induce rapid activation of BAT based on human
fluorodeoxyglucose PET/CT scans. During this time, study participants will be comfortably seated or reclined and
can engage in reading and/or digital entertainment. Rockefeller hospital staff will check on the participants every
30min and monitor for signs of discomfort and/or hypothermia. Following the 3-hour cold exposure period, the
third blood draw sample will be collected as described above. The cold vests are safe for human use, and these
are well established protocols that have been successfully performed by Dr. Cohen’s IRB-approved studies and
others in the metabolism field. These are also the official recommended experimental guidelines employed by
the Brown Adipose Reporting Criteria in Imaging Studies (BARCIST) for humans. 
Re-Warming (3 hours). Following cold exposure, the cold vests will be removed, and participants will be offered
a warm blanket to ease the transition from cold back to warm temperatures. Participants will then be moved to
an adjacent warm room maintained at 30oC and asked to return to the resting position of their choice. Blood
sampling will occur 45 min after the transition to warm temperatures as described above. This will be a critical
sampling period as we hypothesize that the NST program will be shutting down in response to the warm
temperatures and therefore will maximize the potential of identifying regulatory factors that govern the acute
phase of NST silencing. Following blood collection, participants will be provided a second liquid nutrition meal
replacement beverage meeting a third of their dietary reference intakes (DRI) for energy at ~1:15pm to
represent the “lunch” meal. This will ensure that participants continue to remain in the fed state throughout the
study. Participants will then engage in reading and/or digital entertainment for the remainder of the 3- hour
warm exposure period. The last blood collection will take place as described above and we anticipate that these
samples will reveal potential regulatory factors that govern the chronic phase of NST silencing.
Adipose Tissue Biopsy
At the end of both the cold and warm exposure periods, Jeanne Walker, DNP, ANP-BC at the Rockefeller
University will perform a punch biopsy according to established standard operating procedures. Briefly, the
punch biopsy is a minor surgical procedure where a small piece of skin and some underlying fat tissue is
removed from the participants lower abdomen after it has been numbed with local anesthesia (1-2% xylocaine).
One biopsy 6 mm in diameter (about ¼ inch, the size of a pencil eraser) will be obtained. The skin will be closed
with 2 absorbable sutures. Punch samples will be transferred to 1.5 mL microcentrifuge tubes, flash frozen in
liquid nitrogen, and stored in -80oC. Samples will be transported back to the Cohen and Barrow laboratories on
dry ice where they will be processed for downstream transcriptomic analyses.
Role of the Collaborator
Dr. Barrow will obtain approval from the Cornell Ithaca IRB for the specimen analysis taking place there. A copy
of the Cornell RB approval letter will be submitted via an amendment prior to beginning work and any transfer
of materials to that site.
Dr. Joeva Barrow PhD, RD. and her research technician Muying Li, MS. RD. (Cornell University, Ithaca, NY) will
be directly involved in all phases of the study (nutrition assessment, cold and rewarming exposure, and adipose
tissue biopsies). They will reside in NYC for the duration of the study and will be on site. Following completion of
the study, half of all study samples (blood, adipose tissue etc) will be transported to Cornell University on dry ice
for downstream proteomic, transcriptomic, and metabolomic analyses to identify regulatory factors that are
critical for NST silencing and therefore harbor the potential to combat obesity and metabolic disease. The Cohen
laboratory will retain the other half of the samples for complementary rigorous analyses. The Barrow and Cohen
laboratories will maintain regular communication and will each be listed as co-authors on publications in peer-
reviewed journals that arise from each independent group. 
12.10   * Data Analysis
Describe method(s) of data analysis. 
Diet History Questionnaire III (DHQ III) web-based software is integrated with a DHQ III analysis program that
automatically calculates nutrient and food group intakes and the Healthy Eating Index (HEI)-2015 based on

questionnaire responses and produces analysis files. Detailed data output of DHQ III can be found on its
website: https://epi.grants.cancer.gov/dhq3/data.html.
The Barrow laboratory will use the “Guidelines for Data Processing and Analysis of the International Physical
Activity Questionnaire (IPAQ)” as the scoring protocol to analyze data and calculate the Metabolic Equivalents
(METs) values from the short IPAQ responses. The MET values will be converted to Physical Activity Level (PAL)
according to Table 12-1 Intensity and Impact of Various Activities on Physical Activity Level in Adults from the
National Academies of Sciences, Engineering, and Medicine Dietary Reference Intakes for Energy (DRI) 2005.
PAL categories (PALCAT) will be used later for the Estimated Energy Requirements (EER) calculation. PALCAT
includes sedentary (PAL ≥ 1.0 < 1.4), low active (PAL ≥ 1.4 < 1.6), active (PAL ≥ 1.6 < 1.9), and very active
(PAL ≥ 1.9 < 2.5).
Body Mass Index (BMI) will be calculated using the metric system via the BMI Calculator from CDC. Link to the
calculator: https://www.cdc.gov/nccdphp/dnpao/growthcharts/training/bmiage/page5_1.html.
The formulas to calculate EER is from the Table S-3 Summary Table of EER Equations Based on TEE Prediction
by Age, Sex, and Physical Activity: Adults, National Academies of Sciences, Engineering, and Medicine Dietary
Reference Intakes for Energy (DRI) 2023.
Whole blood stored at 4oC from our five collection points will be processed within 24 hours of collection to
extract plasma for proteomic and metabolomics analysis. Briefly, blood samples stored in EDTA-coated tubes will
be centrifuged for 10min at 4oC for 2000 xg to pellet cells. Plasma will be retained and aliquoted into sterile 2
mL microcentrifuge tubes, flash frozen and stored at -80oC for transport to the Barrow and Cohen laboratories.
In regard to the blood samples collected in the non-EDTA tubes, they will be placed at room temperature for 20-
30min to promote clotting, then blood samples will be spun down at max speed and the serum fraction will be
retained and aliquoted into 2mL microcentrifuge tubes and stored at -80oC transport to the Barrow and Cohen
laboratories.
8.8 STATISTICAL MEASURES
All statistics will be performed with the consultation of both the Cornell and Rockefeller University Statistical
Consulting Units that employs dedicated statisticians to assist with research studies. Briefly, human participant
recruitment numbers were calculated based power analysis with an alpha value of 0.05 and an effect size of 10-
20% to yield statistical significance based on previous human studies performed in the field. An n=20 per group
for our proteomic, metabolomic, and transcriptomic analysis will produce high scientific rigor and reproducibility.
Statistics for our proteomic analysis will utilize target peptide signals normalized by total peptide amount with P-
values calculated by Student’s T test with correction for multiple testing using the Proteome Discover 2.4
software. Metabolomics and transcriptomics statistical analyses will be performed by Student’s T test according
to core facility standards and will be confirmed using the GraphPad Prism 9 software.
12.11   * Explain the rationale for the choice of statistical measures and the number of participants
proposed for the study, including the power calculations when applicable.
This is a pilot study that will provide data for power analysis in future studies. A biostatistician will be consulted
to guide clinical data integration and correlations with blood biomarkers and genes discovered in this study.
                                                       
    
12.12   * Will samples be coded?
 Yes  
 No
If Yes, Please describe coding scheme consistent with GCP.  If samples will not be coded, please
provide justification for this proposed departure from GCP practice.
 
JBA-10 1A- Cooling
JBA-10 1B- Rewarming
There are 6 blood draws and 2 optional biopsies.
If available, upload the Data and Sample Sharing Management Plan approved by RU IT.
Version
Title
Category
Expiration
Date
Document
Outcome
View Document
No Document(s) have been attached to this form.
13.0
Participants of Study
13.1   Specify age range of participants: 
* Minimum Age:
18
* Maximum Age:
35

Please note:  If the age of participants indicated is less than 18 years old, you will be prompted to
attach a Pediatric Assent form later on in the submission process.  A link to the Pediatric Assent form
can be found in the Help link to the right, or this form can be downloaded later on in the submission
process.
 
 
13.2   * Indicate the gender(s) of the participants:
Female
Male
Unknown
Not Reported
13.3   * Indicate projected enrollment by race and ethnicity.  See Help for disease/volunteer population
demographics. 
Ethnic Category
Sex/Gender
Females
Males
Unknown or Not
Reported
Total
  Hispanic or Latino
18
16
0
34
  Not Hispanic or Latino
46
40
0
86
  Unknown
  (individuals not reporting ethnicity)
0
0
0
0
  Ethnic Category: Total of All Subjects*
64
56
0
120
                   Racial Categories
  American Indian/Alaska Native
0
0
0
0
  Asian
10
10
0
20
  Native Hawaiian or Other Pacific
Islander
0
0
0
0
  Black or African American
17
16
0
33
  White
31
29
0
60
  More Than One Race
0
0
0
0
  Unknown or Not Reported
6
1
0
7
  Racial Categories: Total of All
Subjects*
64
56
0
120
13.4   Exclusion of Protected Groups:
*Research involving human participants should be designed/conducted to be as broadly inclusive as
possible regarding sex, gender, race, age, and ethnicity. Exclusions regarding these characteristics
require an explanation of the rationale and justification.
Will participants of a specific sex/gender/race/ethnicity/age or other protected group
characteristic be excluded from participation?
  Yes  
  No
13.5   Vulnerable Populations
Indicate whether any of the following populations will be included in the study:
Children
Pregnant Women
Cognitively Impaired Persons
RU Employees
RU Students
Other:
If you checked any of the above, give a brief explanation of the need to use these particular
individuals:
If the participant is a Rockefeller University employee, does she/he work within the Laboratory of the
Principal Investigator or Co-Investigator(s)?
Yes 
No 
N/A 

If the participant is a Rockefeller University student, does she/he work within the Laboratory of the
Principal Investigator or Co-Investigator(s)?
Yes 
No 
N/A 
13.6   *What is the total number of evaluable participants you plan to enroll at Rockefeller University Hospital over the
course of the entire study?
120
13.7   * What is the total number of participants who will need to sign consent at Rockefeller University
Hospital over the course of the entire study to result in the desired number of evaluable participants?
140
13.8   * What is the total number of participants you plan to sign consent at Rockefeller University Hospital
in the next year?
60
13.9   * What will be the total number of evaluable participants at all sites over the course of the entire
study?
120
13.10   Inclusion Criteria
Please list participant inclusion criteria:
Order
Number
Criteria
1 
Age between 18 years old and 35
 
2 
Lean group: BMI is between 18.5 and 24.9. A1C <5.7%
 
3 
Obese group: BMI is >30, A1C <5.7%
 
4 
Obese group with Type II diabetes: BMI is >30, A1C is >6.5%
If on oral medication for diabetes management, A1C may be < 6.5%
The following medications are also acceptable: statins, aspirin, ACEi, ARB. 
 
13.11   Exclusion Criteria
Please list participant exclusion criteria:
Order
Number
Criteria
1 
Diabetes type I (self-report)
 
2 
Diagnosis of thyroid disease (including goiter, hyperthyroidism, hypothyroidism, thyroiditis)
(self-report)
 
3 
Diagnosis with cancer including skin cancer (self-report)
 
4 
Diagnosis or evidence of Raynaud’s Syndrome or systemic sclerosis (self report)
 
5 
A recent diagnosis of COVID-19 (last 2 weeks) or hospitalized at the time of diagnosis with
COVID-19
 
6 
Any vaccine administration within two weeks preceding the study procedure
 
7 
Currently pregnant
 
8 
Currently taking any prescribed medication other than oral contraceptives Treatments for weight
loss or any other supplements that may alter weight or metabolism are not acceptable
Vitamins are acceptable
 
9 
Has consumed nicotine (smoking, inhaling, ingesting) within the last 6 months
 
10 
Has used illicit drugs within the last 6 months (marijuana users are eligible unless consumed in
the last 30 days).
 
11 
Any medical, psychological, or social condition that, in opinion of principle investigators, would
jeopardize the health or well-being of the participant during the study procedure or integrity of
the data
 
12 
Diabetes Type II that is managed by insulin. 
 

13 
Steroid use in the last 30 days to the exclusions
 
14.0
Schedule of Events/Study Plan
14.1  
Instructions:New Studies:
A Schedule of Events is required for all new studies involving interactions with human subjects.
The iRIS Study Plan will not be accepted for new protocols. 
A template Schedule of Events is available on the IRB Website. For any new study, populate the template
with the visits and procedures for the study. 
The content of the Schedule of Events should be consistent with any descriptions of study procedures that
may be in the protocol text and informed consent. 
Attach the completed Schedule of Events document to the Submission Form in the Schedule of Events section.
Existing Studies: For existing studies, investigators may elect to update the existing Study Plan OR may replace the
Study Plan with a Schedule of Events, following the instructions above for new studies.
Attach the Study Plan (an option only for studies with pre-existing Study
Plans):
No Study Plan Templates have been associated.
* What is the total number of outpatient visits for all participants projected for the next
year?
60
* What is the average length of each outpatient visit (in hours)?
3
* What is the total number of Day Patient visits for all participants projected for the next
year?
60
* What is the average length of each Day Patient visit (in hours)?
7
*  What is the total number of inpatient days for all participants projected for the next year?
0
15.0
Consent Procedure
15.1   * This study will use the following types of informed consent:
Informed Consent Form Standard - a standard consent form with instructions for adapting it to your study
Consent Form Genetic- a consent form designed for a study where genetic testing (as defined by NYS law) is
to be done in the CURRENT study
Consent for studies including genome wide sequencing
Pediatric Assent Form (To be used in addition to Consent) for Pediatric patients
Other (e.g., waivers, electronic informed consent)
Links to the Standard Consent, Genetic Testing Consent and the Pediatric Assent forms can be
found in the Help link to the right, or these forms can be downloaded later on in the submission
process.
15.2   * Indicate the consent process to be used.  
   (See Help for CCTS SOP)
Describe how the required information is being presented to participants (consent form, orally,
information sheet, etc.).  Attach a copy of what is being presented to participants (usually the ICF and
Assent forms).
Prior to the initiation of any study related procedures, the potential subjects will be given a copy of the most
recent IRB stamped and approved informed consent form to read. Additionally, the PI or study staff member who
has been designated and is proficient in the consent form process will discuss the specifics of the study including
but not limited to the purpose of the research, procedures, time commitment, required tasks, test article or
device, alternative treatments, benefits, risks, confidentiality etc. in a comprehensible (non-scientific) manner,
using language readily understandable by the subject. Subjects will be told that participation is voluntary and
that, if they do not give informed consent, they will not be penalized. The person obtaining informed consent will
assure the voluntariness of the subject. THe Zoom consent process will be obtained by having participants sign
the eConsent via REDCap according to the established eConsent SOP and will be enrolled in the study. 
Describe the circumstances under which consent will be obtained, where the process will take place
and any waiting period between informing the prospective participant and obtaining consent. 
All subjects will be consented by Zoom. Zoom consenting will be conducted as per the IRB-approved RU
electronic Consent Process Guidelines. The subject will receive the consent form in advance of a Zoom
conversation in which the study will be discussed and all questions answered. The subject will return a signed
consent form to the person obtaining consent, who will then sign and date the consent form, file the original, and
return a copy to the subject.

Describe the experience of the investigators designated for this task in the DOA in obtaining consent
from participants.
The following staff, Joeva Barrow and Muying Li have demonstrated competency in consenting participants for
participation in research studies and are certified. This competency is based on attending a consenting class
which includes regulations, the do’s and don’ts and didactic role playing. It also includes observing the
consenting process as performed by an experienced consenter and then consenting a participant to participate in
a research study while being observed by the experienced consenter.
How will it be determined that the participants or the participants' authorized representatives
understand the information presented? 
The "Teach Back" method will be used in the clinical research setting to ask research participants to repeat or
“teach back” the information, concepts and directions that the staff member has attempted to convey to the
participant. This method is used to assess comprehension and retention of protocol requirements, adverse event
information, risks and benefits, and the participant's rights described in the Informed Consent process.
If English is not the participants' native language, how will written and/or verbal translation be
provided?
For unexpected or isolated participants who are candidates for this study, but for whom English is not a primary
language, a translator provided through Pacific Interpreters will be used to facilitate the explanation of the study,
either in person or through Zoom consenting.
Will any participants be cognitively impaired so that they may not have the capacity to give consent?
  Yes  
  No
For participants where it has been determined that they lack the capacity to give consent, describe the
provisions for obtaining consent from the participants' legally authorized representative.
Zoom consent process will be performed in accord with the RU SOP on Virtual Visits; a copy of the document is
shared by Study Correspondence.
15.3   * Based on the demographics, will this study's participant population require foreign language
consent form? 
  Yes  
  No
15.4   * This study's consent procedure will require the following waivers:  
(See Help for additional information.)
Waiver of one or more elements of informed consent, 45 CFR 46.116(f) 
Waiver of documentation of informed consent, 45 CFR 46.117(c) 
No waiver is requested 
15.5   Will you obtain a Certificate of Confidentiality (CoC) for this study?
  Yes  
  No
15.6   * Does this study include video/audio recording, photography or other electronic recording of human
participants?
  Yes  
  No
16.0
Recruitment and Advertising
For assistance consult CRSO to create a robust Recruitment Plan see Help.
16.1   * What is the plan for recruitment?
What is the plan for recruitment?
Overview: The CRROSS seeks to prescreen up to 200 healthy volunteers between the ages of 18-35 to
achieve the overall goal of 120 evaluable participants. 
Feasibility and Assessment:
Incentives:1) Altruism; 2) Interest in study topic 3) Compensation 
Challenges:  1) Overall impact of the Covid-19 pandemic may dissuade individuals from voluntarily
participating in research studies; 2) Long study visits, 3) Age eligibility of 18-35 is somewhat narrow for
Type-2 diabetics and obesity 4) Compensation is modest and may need to be increased to provide
greater incentive to participate.
Issues relevant to rapid accrual:
Positive:  1) Existing cohort of healthy volunteers in the repository; 2)With the exception of members
of the PI’s laboratory, RU employees and students are allowed to participate in the study
Negative: 1) High no-show turnout for healthy participant studies 2) Study involves visit lasting up to
almost 7 hours; 3) Participants must undergo12 hour fasts and refrain from caffeine prior to the two
study visits, 4) Multiple blood draws during main study visit over the course of almost 7 hours, 5)

Anticipated discomfort from the various study procedures, including prolonged cold exposure, optional
punch biopsies and consuming liquid nutrition in place of solid foods during main study visit.
Projected Time to Accrual Completion (PTAC):
The research team plans to screen 2 participants 3 days per week (M-W) 
Factors Affecting Predicted Time to Accrual Completion
Weeks
Volunteers will be prescreened and referred for remote consenting in advance of study visits.
This should reduce no-shows and increase screen/enrollment ratio.
-----
The research team plans to screen 2 consented participants x 3 days per week to start, which
translates to enrolling up to 6 participants per week (120÷6 = 20).However, given the high
likelihood of screen outs due to eligibility criteria, an additional 20 weeks has been added to the
predicted time frame(20+20 = 40). 
40
Anticipatedstartup,add1 2weeks;ifassaynotready,addestimatedtimetoreadiness
2
Addanyvacationtimewhenscreen/visitcapacitywillbereduced
---
RecruitmentistooccurduringAugust?add2weeksduetohistoricalslowing
2
RecruitmenttooccuracrossDec Januarytimeframe;add2weeksforunitclosure
2
Knownanticipatedmaternityleave,otherLOAofkeystaff–addest.weekslostcapacity 
--
StafforKSPchanges–addonboardingtime-
--
Stafftravelformajorconferences–addweekslostcapacity
--
Institutionalinterruptions(graduation,symposiumdays,etc.)addteamestimate
--
Projected Time to Accrual Completion (PTAC) 46
Recruitment Implementation:
Advertising- CRROSS will advertise on RU Classifieds, Craigslist, and ResearchMatch. Volunteers will
also be drawn from the Clinical Conductor Repository.   
Centralized Call Management – CRROSS will work with the research team to develop a protocol-
specific pre-screening script based on IRB approved protocol eligibility criteria to prescreen volunteers
who call 1800RUCARES. Potentially eligible candidates will be scheduled for the study team for further
screening. CRROSS staff will also call volunteers based on Repository queries described above.
Research teams are responsible to provide timely updates on pre/screening outcomes by updating
volunteers’ Study Status in Cerner. The Recruitment team uses screening outcomes to review progress
and strategy to keep enrollment on target.
Please describe how the Recruitment Plan addresses recruitment of the volunteers
consistent with the demographics of the condition under
study: (referenceCensus,Maps,CDCdata)
People of all races and genders between the ages of 18-35 will be eligible to pre-screen for the
study, exceptfor RU employees and students in the Principal Investigator’s laboratory. RU employees
and students who are not affiliated with the PI’s laboratory may participate in the study if they meet
eligibility requirements.  
We will also be using flyers distributed around RU and surrounding areas. 
16.2   *From the date of final IRB approval, how long will it take to complete enrollment of
the study?
6 Months 
12 Months 
18 Months 
24 Months 
More than 2 years (specify in years) 
16.3   This Study
Involves an intervention or comparison and a defined enrollment target 
Is a natural history study with expected annual enrollment over many years 
Is an exploratory mechanistic study 
Other 
16.4   This Study will enroll:
Healthy volunteers 

Individuals affected with a specific disease/disorder 
Both 
16.5   * Do you plan on using the Research Participant Repository (RKO-0648) ?
 Yes  
 No
16.6   * Are you screening or recruiting from or through a record review of an existing patient database of a
healthcare provider? 
 
  Yes  
  No
16.7   * Please describe how the Recruitment Plan addresses recruitment of the volunteers consistent with
the demographics of the condition under study:  
Through our plan to advertise locally and query the volunteer repository, we anticipate being able to enroll 120
healthy participants representative of a range of races, ethnicities and genders.
16.8   * Do you plan to advertise directly to potential volunteers?  (As opposed to relying on practitioner
referrals  or flyers to practitioners)
 Yes  
 No
16.9   * Do you plan to use the free, web-based volunteer registry, ResearchMatch.org, as a recruitment
tool?
 Yes  
 No
17.0
Research Participant Repository (RKO-0648)
17.1   This protocol, will be linked with the Research Volunteer Screening/Recruitment Data Repository run by the
Recruitment staff and the Clinical Research Support Office (protocol RKO-0648-1008).   In order to participate in the
generation of the Repository the PI will enter into a Collector/Collaborator agreement regarding the Repository. The
role of Collector/Collaborator is to contribute to the Repository the name, contact and demographic information,
recruitment referral information, and screening outcome information, as well as appropriate protocol specific
screening information, of volunteers who are screened by telephone or in person for entry into the protocol
regardless of the screening outcome. In addition to screening volunteers for the PI's current study, verbal consent
will be obtained from the volunteers regarding their willingness to be contacted in the future about possible
additional research studies. This permission may be obtained by the Recruitment office staff through the central Call
Center.  If the  PI receives calls directly from participants for initial prescreening, then the PI is responsible for
collecting the required information and conveying it to the Recruitment staff for data entry.  The consent or
withholding of permission will be recorded in the Repository as will the name of the person who obtained the
permission. A volunteer’s permission or declination will not affect their eligibility for my current protocol, or future
protocols. The Recruitment staff of the Clinical Research Support Office may gather the Repository information and
request the verbal consent of the volunteer for re-contacting on my behalf as part of our recruitment plan.   In order
to benefit from the Repository,  the PI will enter into a Recipient/Collaborator agreement with the Repository.  The
Recipient/Collaborator may receive from the Repository pre-screened lists of potentially eligible participants for
his/her study as a means to facilitate recruitment. The Recruitment staff will prepare the Repository queries
according to the protocol eligibility requirements and available Repository information, and may re-affirm permission
to re-contact volunteers as necessary. The PI may use the information and names in the list from the Repository only
for the current study and may not save the list to use for a future study of his/her own, nor may he/she share the
list with colleagues for other studies."
18.0
Utilization of ResearchMatch.org 
18.1   Utilization of ResearchMatch.org for Recruitment
 
Basic information regarding this tool:
 
ResearchMatch.org is a national electronic, web-based recruitment tool that was created through the Clinical
& Translational Science Awards Consortium in 2009 and is maintained at Vanderbilt University.  There is no
cost for researchers at participating institutions in the ResearchMatch.org Network to use ResearchMatch.org.
The Vanderbilt IRB provides oversight for ResearchMatch.org as a recruitment tool and this has been
documented within the ResearchMatch.org IRB Letter of Understanding which was executed by Dr. Gotschlich
in October, 2009.  However, individual requests to use ResearchMatch.org as a recruitment tool must be
submitted to this institutions’ IRB.
Registration:
 
This recruitment tool may be utilized once the PI or research staff registers for recruitment access through
ResearchMatch.org and the Institutional Liaison provides approval.
The ResearchMatch.org Institutional Liaison will review the study information and evidence of IRB approval.
He/she will set the researcher’s expiration date to mirror that of the study’s IRB approval.
Search Capability:
 
After being granted recruitment access, the researcher can search for appropriate matches amongst the non-
identifiable ResearchMatch.org Volunteer profiles in the system.  He/she can enter study inclusion/exclusion
criteria in the ResearchMatch.org Search Builder which will yield a list of potential matches to the study’s
criteria. 
Contacting ResearchMatch.org Volunteers:
 

Once yielding a list of potential matches (ResearchMatch.org Volunteers), the researcher will send out IRB-
approved content that will be the initial recruitment message that these volunteers receive about the study
through ResearchMatch.org. The study’s recruitment message will be inserted into the standard
ResearchMatch.org electronic notification that informs possible matched Volunteers that he/she has been
identified as a potential match for the study.  The secure ResearchMatch.org clearinghouse will route this
standard ResearchMatch.org email notification. These potential matching volunteers will have the option of
replying yes, no, or not respond through a set of quick links available in this notification to the study
announcement. THE CONTACT MESSAGE WILL NOT INCLUDE THE STUDY’S DIRECT CONTACT INFORMATION
(e.g. EMAIL, PHONE).  By responding yes, the Volunteer has authorized ResearchMatch.org to release his/her
contact information to the researcher.  The researcher will be responsible for managing this contact
information as called for by this IRB-approved study protocol. 
Study Management in ResearchMatch.org:
 
Researchers (and the Liaison) can view information regarding his/her study’s status in ResearchMatch.org
(e.g. number of volunteers contacted for the study via ResearchMatch.org to date, response rate of volunteers,
etc.).  ResearchMatch.org will also be collecting aggregate data regarding the status of ResearchMatch.org
volunteers within the study. Volunteers consent to this within the ResearchMatch.org Volunteer Agreement.
This information will allow the researcher to indicate where the Volunteer currently stands within the
recruitment process and thus will help the researcher monitor the utility and effectiveness of using this
resource (e.g. Did not contact, Not eligible, Enrolled, Completed, etc.).
19.0
Potential Benefits to Participants
19.1   * Will participation in this study provide direct benefits to the participant?
  Yes  
  No
20.0
Potential Risks to Participants
20.1  
*  Describe any potential risks: physical, psychological, social, legal or other and assess their
likelihood and seriousness. Indicate risks both to the participants and to the embryo or fetus if the
participant is or may become pregnant.  Please provide the potential risks below:
Potential risks associated with venipuncture include discomfort or pain, ecchymosis, bleeding, phlebitis and
infection at the needle insertion site. Additional risks include lightheadedness and a vasovagal response.
Potential risks associated with wearing a cooling jacket for 3 hours is feeling uncomfortable due to the coolness.
There is a rare risk of hypothermia while wearing the cooling jacket.
Potential risks associated with an overnight fast and fasting throughout the procedure are feeling hypoglycemic
and hungry.
The potential risk associated with the BodPod is feeling claustrophobic.
Potential risks of biopsy: A punch biopsy produces a small scar. Other potential side effects include pain,
bleeding, or bruising at the site.  Rarely a patient may develop a superficial skin infection.  In people prone to
keloid formation, a biopsy may heal with a keloid.  Occasionally people may faint or become lightheaded during
the procedure.
21.0
Procedures to Minimize Risks
21.1   * Describe the procedures for protecting against or minimizing any potential risks, and include an
assessment of their likely effectiveness. Include a discussion of confidentiality safeguards, where
relevant, and arrangements for providing medical treatment, if needed.
Venipuncture will be conducted by trained staff.
To assess for evidence of hypothermia, tympanic temperature will be monitored every 15 minutes (+/- 5
minutes) Participants will also complete a questionnaire on an iPad every 15 minutes (+/- 5 minutes) to assess
their level of comfort.
The cooling vest will be worn over a hospital gown to prevent skin contact or damage. The cooling jackets used
for this study have been used multiple times and have been shown to be safe. We will employ the established
adaptive cooling method where the cooling temperature is set to 2oC above an individual’s shivering threshold.
How to minimize risk for punch biopsy: Skin/fat punch biopsy will be performed by an experienced clinician
approved by the Medical Staff credentialing committee after completion of training per the RUH standard
operating procedure. The procedure will be performed using sterile technique. The participant will be instructed
verbally and in writing on wound care, signs and symptoms of infection, expected healing schedule, and on-call
contact phone numbers. He/she will be provided wound care supplies. The participant will be contacted by the
study team within 2-3 days post biopsy to monitor healing and address any concerns. Absorbable sutures rwill be
used so patients will not need to return for suture removal.
A warm drink and snack will be offered after the cooling period is complete to aid with rewarming and feeling
hungry.
For data protection, only coded samples and data are shared between the lab and the collaborator.
22.0
Alternative Methods or Treatments
22.1   * Describe alternative methods or treatments for the disease(s) under study, if any, that were
considered and why they will not be used:  
The study does not involve any treatments. The alternative to participation is not to participate. 

23.0
Data and Safety Monitoring
This section describes the Data and Safety Monitoring Plan (DSMP) required
of each protocol undertaken at the CCTS according to HRPP and NIH policies
Notice 98 -084 and Notice 00-038, as cited in Help Sections below.  
Depending on the level or risk and trial phase, some protocols will need Data
and Safety Monitoring Boards.
23.1   * Overall Risk Classification
An estimate of risk is necessary to evaluate the adequacy of the planned monitoring.  The HELP
section provides guidance in making the risk assessment. 
Read the risk definitions and examples of risk in the HELP section and select the risk category that
best describes the current study. 
If your assessment differs from the definitions the HELP section, describe any factors that modify
your judgment of the overall risk in the text box after the risk designation.
MINIMAL RISK 
LOW RISK 
MODERATE RISK 
SIGNIFICANT RISK 
Please provide any optional description(s):
23.2   Protocols Involving Minors
The chance of direct benefit to the child, or to understanding a disorder not otherwise understood,
may be major factors in justifying more than minimal risk in research involving children.  
Based on the above definitions, please specify your study's risk classification below:
NOT GREATER THAN MINIMAL RISK (the risk of daily life to a healthy child living in a safe environment) 45
CFR 46.404 
GREATER THAN MINIMAL RISK WITH DIRECT BENEFIT TO PARTICIPANT; 45 CFR 46.405 
GREATER THAN MINIMAL RISK, NO DIRECT BENEFIT, BUT BENEFIT TO UNDERSTANDING OF PARTICPANT'S
DISORDER; 45 CFR 46.406 
RESEARCH NOT OTHERWISE APPROVED PRESENTING OPPORTUNITY TO UNDERSTAND, PREVENT OR
ALLEVIATE SERIOUS PROBLEM AFFECTING CHILDREN 45 CFR 46.407 (cannot be approved by IRB; requires
public comment) 
23.3   DSMB
1. The NIH requires that all SIGNIFICANT RISK protocols have a Data and Safety Monitoring
Board and provide information about the expertise and independence of that Board
2. Phase III trials require a Data and Safety Monitoring Board,
3. A DSMB may be appropriate for some Phase I and II protocols. (See Help for examples.)
4. It is the investigator's responsibility to report to the IRB, the findings and recommendations of
the DSMB as they become available.
Please specify:
A DSMB is required for this study 
A DSMB is not required for this study 
Unsure 
If a DSMB is not required, but is being constituted for other reasons, please explain:
23.4   * Safety Review
Select one:
Safety Review is conducted as follows: Laboratory results for research volunteers will be reviewed in a timely
manner, usually within 24 hours of receipt by a licensed practitioner. The potential clinical significance of any
abnormal finding will be documented in the medical and research record(s), and an appropriate plan or
referral developed. The PI's review of safety issues at research team rounds will be documented in the
meeting minutes. 
Protocol Specific 
23.5   Monitoring

Monitoring Personnel:  See Help Bubble to the right.
Internal Monitoring
The PI or his/her designee shall conduct internal monitoring to assure the safe and proper conduct of
the protocol and all the elements list above in monitoring, following the general principles of quality
management.  The intensity and frequency of internal monitoring will depend on the protocol risk to
participants, the experience of the PI and research team, rate of enrollment, and specific details of the
protocol. 
Internal monitoring of informed consent and eligibility documentation will be conducted by the
research team shortly after enrollment begins.  Internal monitoring activities will be documented by
logs, meeting minutes or other systematic means.  
Specify the research team members who will conduct the internal monitoring of the study (see Help
for who may monitor):
The PI or their designee shall conduct internal monitoring to assure the safe and proper conduct of the protocol
and all the elements list above in monitoring, following the general principles of quality management.  The
intensity and frequency of internal monitoring will depend on the protocol risk to participants, the experience of
the PI and research team, rate of enrollment, and specific details of the protocol.
Internal monitoring of informed consent and eligibility documentation will be conducted by the research team
shortly after enrollment begins.  Internal monitoring activities will be documented by logs, meeting minutes or
other systematic means.
Specify the research team members who will conduct the internal monitoring of the study (see Help for who may
monitor):
The PI will be taught how to conduct internal monitoring of her study.
For new investigators:  Internal monitoring should be conducted at least monthly by new investigators until there
are essentially no findings to correct at each review.
For new investigators:  Internal monitoring should be conducted at least monthly by new investigators
until there are essentially no findings to correct at each review.
External Monitoring
*  Is external monitoring planned for this protocol?
Yes 
No 
Unsure 
If external monitoring is planned, please specify (see Help for who may monitor):
(Significant Risk) External monitoring will occur at least every six weeks unless there is no enrollment 
(Moderate Risk) External monitoring will occur at least quarterly 
(Low or Minimal Risk) External monitoring will occur at least annually 
If external monitoring is planned, please specify the name of the monitor:
Note that copies of external monitoring reports must be supplied to the IRB and the CRSO as soon as they
are made available
Additionally, audits of the research records of minimal, moderate or significant-risk protocols may be
performed by the CRSO staff on a random basis or as part of a prospectively identified auditing plan. 
23.6   Adverse Event Classification
Adverse events are classified by definition, severity, and association with the investigational trial.
 
Definition of an Adverse Event
Any unfavorable or unintended sign (including abnormal lab findings), symptom or disease temporally
associated with the use of a medical treatment or procedure, or protocol,  regardless of whether it is
considered related to the medical treatment or procedure or protocol.
 
Definition of a Serious Adverse Event
Any unanticipated event that involves the following:
o   results in death
o   is life-threatening
o   requires hospitalization or prolongs existing hospitalization
o   results in persistent or significant disability/incapacity
o   is any medical event which requires treatment to prevent one of the outcomes listed above
Other events can be classified as "serious adverse events" at the discretion of the PI.
 
Definition of Anticipated/Expected Adverse Event
Any adverse event, which has been reported in the Investigator's Brochure, package insert, safety reports,
clinical protocol, consent form or listed in the NCI agent-specific Expected Adverse Event List3, is classified as
an expected adverse event.  The investigator must provide the available data of known adverse events and
toxicities that have been associated with the study drug, device, intervention, or procedures.  This information
helps to define the level of risk of the trial and enables safety monitoring.  A minimal risk trial may not have
any defined risks and a statement to that effect is sufficient to meet the DSMP requirements.
 
Definition of an Unanticipated/Unexpected Adverse Event
Any adverse event that is not consistent with the known, predicted possible effects of the research protocol. 
An unexpected adverse event varies in nature, intensity or frequency from information on the investigational
product provided in the Investigator's Brochure, package insert, safety reports, clinical protocol, or listed in
the consent form.

 
Definition of an Unanticipated Problem (UaP)
A UaP is an event or circumstance that meets all the following three criteria: [1] the nature, severity,
frequency of the event(s) or information was not expected in the descriptions in the study documents or the
characteristics of the participant population being studied; [2] there is a reasonable possibility that the
procedures involved in the research caused or are linked in a significant way to the problem; [3]the event or
information suggests that the research places particpants or others at a greater risk of harm than was
previously known or recognized (including physical, psychological, economic, or social harm.
 
 
Grade and Relatedness of Adverse Events:
Adverse Events are graded for severity and scored for relatedness to the protocol, according to a published
scale.  Several standardized AE Reporting scales are available.  (See Help for links to these scales.)  
* Please indicate the scale you intend to use:
CTC v2.0 ( http://ctep.info.nih.gov/reporting/ctc.html ) 
CTCAE v3.0 ( http://ctep.info.nih.gov/protocolDevelopment/electronic_applications/docs/ctcaev3.pdf) 
CTCAE v4.0 (http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_8.5x11.pdf) 
CTCAE v5.0
(https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf) 
AIDS Clinical Trials Group (http://aactg.s-3.com/) 
Other 
23.7   Reporting Adverse Events
All AEs will be reported to the IRB at least annually.
Reporting Serious AEs
Serious Adverse Events, (SAEs) will be reported to the IRB according to policy, within two working days of
identification of the SAE.
Select all that apply:
SAEs will be reported to the Sponsor and or ESCROW
SAEs will be reported to the sponsor within how many days of the event?
 
SAEs will be reported directly to the FDA, per 21 CFR 312
      SAEs must be reported directly to the FDA within 7 days of the event by the investigator/sponsor.
SAEs will be reported to another entity
Describe:
Reporting Unanticipated AEs:
Select all that apply:
UAEs will be reported to the IRB
UAEs that are related and greater than moderate severity must be reported to the IRB according to
policy, within two working days of identification of the UAE. 
 
UAEs will be reported to the Sponsor
UAE will be reported to the sponsor within how many days of the event?
UAEs will be reported to the FDA, per 21 CRF 312
UAEs will be reported to the FDA, per 21 CRF 312, within 15 days.
UAEs will be reported to another entity
Describe:
23.8   Reporting Unanticipated Problems
Unanticipated problems involving risks to participants or others will be reported to the IRB and the CRSO
within five working days.

23.9   CLIA/CLEP
 
Only laboratory and research tests that are CLIA/CLEP certified or waived may be used to determine
eligibility, shared with research volunteers, and used in clinical decision making.
Select if applicable:
This study includes tests that are not CLIA/CLEP certified; the results of such tests will not be used in clinical
decision making, or to determine eligibility, or shared with participants or their health care providers.
23.10   Tissue Repository
Human Tissue and Data Repositories collect, store, and distribute human tissue materials and or
data for research purposes. Repository activities involve three components: (i) the collectors of
tissue samples\data;  (ii) the repository storage and data management center; and (iii) the recipient
investigators.
*  Select one:
I DO NOT intend to collect, store, and distribute human tissue materials for research purposes 
I DO intend to collect, store, and distribute human tissue materials for research purposes, therefore this
protocol entails the Operation of a Tissue Repository. The IRB requires that the protocol specify the
conditions under which data and specimens may be accepted and shared, and ensuring adequate provisions
to protect the privacy of participants and maintain the confidentiality of data. 
If you do intend to collect, store, and distribute human tissue materials, you will be asked to upload
the following documents later on in the submission:
A Sample collection protocol (for tissue collector collaborators to follow) and informed consent
document for distribution to tissue collectors and their local IRBs.
A Certificate of Confidentiality (to protect confidentiality of repository specimens and data).
A Recipients Agreement describing the commitment of the recipient to preserve the anonymity
of the samples shared.
24.0
Toxicity Management and Stopping Rules
24.1   * Describe any drug toxicity or other conditions under which the participation of a participant or the
conduct of the study would be stopped in order to maximize safety (e.g., toxicity management and
stopping rules):
 
The study will be stopped for safety reasons related to symptomatic hypothermia (e.g., shivering, slurred speech
or mumbling, shallow breathing, weak pulse, clumsiness, or loss of coordination, drowsiness, or confusion.
* Indicate withdrawal criteria and procedures below:
If the participant exhibits any major discomfort or hypothermia, the experiment will be stopped, the cooling
jacket removed, and the participant will be warmed with blankets.
The participant will be withdrawn from the study if the participant’s temperature reaches 35.5 degrees Celsius.
25.0
Compensation/Costs
25.1   *Will any compensation be offered to participants in return for their participation, e.g., direct
payment, medical care, tests, etc.?  
No 
Yes (Please describe) 
Please Describe
Participants will be compensated up to $300 upon completion of the study, participants who complete both
biopsies will receive an additional $100 in cash.
25.2   * Will there be any costs to participants associated with their participation in research?
  Yes  
  No
26.0
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26.1    Enter your bibliography below:
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Blüher M, Goodyear LJ, Hotamisligil GS, Stanford KI, Tseng YH. The cold-induced lipokine
12,13-diHOME promotes fatty acid transport into brown adipose tissue. Nat Med. 2017
May;23(5):631-637. doi: 10.1038/nm.4297. Epub 2017 Mar 27. Erratum in: Nat Med. 2017
Nov 7;23 (11):1384. PMID: 28346411; PMCID: PMC5699924.

10. Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O, Holman AR, Tal I, Palmer MR,
Kolodny GM, Kahn CR. Cold but not sympathomimetics activates human brown adipose
tissue in vivo. Proc Natl Acad Sci U S A. 2012 Jun 19;109(25):10001-5. doi:
10.1073/pnas.1207911109. Epub 2012 Jun 4. PMID: 22665804; PMCID: PMC3382513.
11. Chondronikola M, Volpi E, Børsheim E, Porter C, Annamalai P, Enerbäck S, Lidell ME, Saraf
MK, Labbe SM, Hurren NM, Yfanti C, Chao T, Andersen CR, Cesani F, Hawkins H, Sidossis
LS. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity
in humans. Diabetes. 2014 Dec;63(12):4089-99. doi: 10.2337/db14-0746. Epub 2014 Jul
23. PMID: 25056438; PMCID: PMC4238005.
12. National Academies of Sciences, Engineering, and Medicine. 2023. Dietary Reference
Intakes for Energy. Washington, DC: The National Academies
Press. https://doi.org/10.17226/26818
13. Saito M, et al. High incidence of metabolically active brown adipose tissue in healthy adult
humans: effects of cold exposure and adiposity. Diabetes. 2009;58(7):1526–1531.
doi: 10.2337/db09-0530
14. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ,
Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N
Engl J Med. 2009 Apr 9;360(15):1500-8. doi: 10.1056/NEJMoa0808718. Erratum in: N Engl
J Med. 2009 Apr 30;360(18):1917. PMID: 19357405.
15. Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA, Enerbäck S, Kinahan PE,
Lichtenbelt Wv, Lin FI, Sunderland JJ, Virtanen KA, Wahl RL. Brown Adipose Reporting
Criteria in Imaging STudies (BARCIST 1.0): Recommendations for Standardized FDG-
PET/CT Experiments in Humans. Cell Metab. 2016 Aug 9;24(2):210-22. doi:
10.1016/j.cmet.2016.07.014. PMID: 27508870; PMCID: PMC4981083.
16. Yoneshiro T, Wang Q, Tajima K, Matsushita M, Maki H, Igarashi K, Dai Z, White PJ,
McGarrah RW, Ilkayeva OR, Deleye Y, Oguri Y, Kuroda M, Ikeda K, Li H, Ueno A, Ohishi M,
Ishikawa T, Kim K, Chen Y, Sponton CH, Pradhan RN, Majd H, Greiner VJ, Yoneshiro M,
Brown Z, Chondronikola M, Takahashi H, Goto T, Kawada T, Sidossis L, Szoka FC, McManus
MT, Saito M, Soga T, Kajimura S. BCAA catabolism in brown fat controls energy homeostasis
through SLC25A44. Nature. 2019 Aug;572(7771):614-619. doi: 10.1038/s41586-019-
1503-x. Epub 2019 Aug 21. PMID: 31435015; PMCID: PMC6715529.
17. Shinoda K, Luijten IH, Hasegawa Y, Hong H, Sonne SB, Kim M, Xue R, Chondronikola M,
Cypess AM, Tseng YH, Nedergaard J, Sidossis LS, Kajimura S. Genetic and functional
characterization of clonally derived adult human brown adipocytes. Nat Med. 2015
Apr;21(4):389-94. doi: 10.1038/nm.3819. Epub 2015 Mar 16. PMID: 25774848; PMCID:
PMC4427356.
18. O'Neill SM, Hinkle C, Chen SJ, Sandhu A, Hovhannisyan R, Stephan S, Lagor WR, Ahima
RS, Johnston JC, Reilly MP. Targeting adipose tissue via systemic gene therapy. Gene Ther.
2014 Jul;21(7):653-61. doi: 10.1038/gt.2014.38. Epub 2014 May 15. PMID: 24830434;
PMCID: PMC4342115.
19. Yu J, Vogt MC, Fox BW, Wrobel CJJ, Fajardo Palomino D, Curtis BJ, Zhang B, Le HH,
Tauffenberger A, Hobert O, Schroeder FC. Parallel pathways for serotonin biosynthesis and
metabolism in C. elegans. Nat Chem Biol. 2023 Feb;19(2):141-150. doi: 10.1038/s41589-
022-01148-7. Epub 2022 Oct 10. Erratum in: Nat Chem Biol. 2022 Nov 18;: PMID:
36216995; PMCID: PMC9898190.
20. Le HH, Wrobel CJ, Cohen SM, Yu J, Park H, Helf MJ, Curtis BJ, Kruempel JC, Rodrigues PR,
Hu PJ, Sternberg PW, Schroeder FC. Modular metabolite assembly in Caenorhabditis
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22. Cero C, Lea HJ, Zhu KY, Shamsi F, Tseng YH, Cypess AM. β3-Adrenergic receptors regulate
human brown/beige adipocyte lipolysis and thermogenesis. JCI Insight. 2021 Jun
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23. O'Mara AE, Johnson JW, Linderman JD, Brychta RJ, McGehee S, Fletcher LA, Fink YA,
Kapuria D, Cassimatis TM, Kelsey N, Cero C, Sater ZA, Piccinini F, Baskin AS, Leitner BP, Cai
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Herscovitch P, Chen KY, Cypess AM. Chronic mirabegron treatment increases human brown
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Lichtenbelt WD. Brown adipose tissue in morbidly obese subjects. PLoS
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27.0
Appendices
27.1   Enter your appendices below:
28.0
Funding
28.1   * Do you have sufficient financial resources to support your study? 
 Yes  
 No
28.2  
If this study is/was pilot funded, please specify dates of funding:
From date:
To date:
28.3   Source of investigational agents:
N/A (no investigational agents) 

Provided by a pharmaceutical sponsor/partner with funding as described below 
Provided by a pharmaceutical sponsor/partner without additional funding 
Provided by investigator, participants, or other 
28.4   Specify funding by Rockefeller University, industry sponsor and/or grant:
   Search for a sponsor   
 Sponsor
Funding
Rockefeller
University
  Paul Cohen Laboratory.
Industry
 
Grant
 
Pilot
Award
 
28.5   List grants in which this study is named:
PHS or Non-PHS Program
Grant Number
Grant Name
From Date
To Date
No results found
29.0
Clinical Services
29.1   *What is the general health status of your study group(s)?
Well/Minimally Ill
Moderately Ill
Severely Ill
Other
Not Applicable
If other than Well/Minimally Ill, please describe:
29.2   * Does your study group have special care needs? 
  Yes  
  No
29.3   * Does your study have special equipment needs? 
 Yes  
 No
If Yes, please describe:
Polar Cooling jacket; provided by the research team. 
29.4   * Will you require storage space on the clinical units for supplies to conduct this study?
 Yes  
 No
If Yes, please describe:
Cooling jacket stored in locked closet on the RUH unit. 
29.5   * Is special training of hospital staff required?
  Yes  
  No
30.0
Pharmacy Services
30.1   * Does the study require Pharmacy Services?

  Yes  
  No
31.0
Bionutrition
31.1   * Will study require patient meals? 
 Yes  
 No
If Yes, please specify:
Type of Diet
In/Outpatient
Pack Meal
Standard
Inpatient
Outpatient
Pack Meal 
Therapeutic
Inpatient
Outpatient
Pack Meal 
Research Diet
Inpatient
Outpatient
Pack Meal 
Formula Diet
Inpatient
Outpatient
Pack Meal 
Nutrient(s) to be controlled (specify):
Visit #1:  The BodPod will be ordered for the participant on visit 1.  The BodPod will be the first scheduled
procedure on visit 1. It will be conducted first thing in the morning, about 9 am.  
The participant will have an in.pt. hot breakfast and hot lunch ordered.  Bionutrition will administer either meal,
as requested.
Visit #2. The Barrow research team will then formulate an individualized tailored nutrition beverage that will
meet 33% of each participants’ daily EER. This nutrition beverage (Katefarm Nutrition Shake which is USDA
Organic, Non-GMO, plant-based, vegan, and does not contain milk, eggs, fish, shellfish, tree nuts, peanuts,
wheat, or soybeans https://vpn.rhttps://shop.katefarms.com/products/nutrition-shake) will be provided to
participants on Visit #2 to ensure that study participants are maintained at nutrient baseline and maintained in a
fed state throughout the study. The formula will be provided to Rockefeller Bionutrition department, by the
Barrow research team, for storage, preparation and administration.
31.2   Will meal times be altered? 
 Yes  
 No
If Yes, please explain:
Meals will be offered whenever the participant is ready for them. 
31.3   Does the protocol require any of the following activities?
Food Frequency Questionnaire
Bod Pod/ Anthropometric Measurements
Diet History/ Food Records
Diet/ Nutrition Education
31.4   Will food be provided to caregiver, parent or significant other?  
  Yes  
  No
31.5   For metabolic diets, is diet homogenization required for nutrient analysis
 by independent lab?
Yes 
No 
N/A 
32.0
Clinical and Translational Research Facilitation Office
32.1   Indicate navigation assistance requested and/or received in the development of the study:
Requested
Received
Protocol Development

Protocol Implementation
Protocol Conduct
ACCTS/IRB Submission
32.2   Indicate additional education assistance requested and/or received in the development of the study:
Requested
Received
IND
IDE
Team Science Education
Study Progress Meeting
Investigator Responsibilities
Regulatory Binder/Folder
Source Documentation
Participant Involvement in
Research
33.0
Clinical Research Support Office Resources (CRSO)
33.1   Indicate regulatory input assistance requested and/or received in the development of the study:
Regulatory Support/Design
Requested
Received
General,
Vulnerable Populations,
Minors, Group Harms
IND/IDE advice, assistance,
and referral
Informed Consent/Assent
Data Safety Monitoring Plan
Clinical Trial Registration
Plan For Return of Research
Results
Audit/Monitoring Service,
Referrals, SOPs
33.2   Indicate recruitment assistance requested and/or received in the development of the study:  
Recruitment of Participants
Requested
Received

Recruitment Planning and/or
written Plan
Advertising Strategy, Content,
Placement
Repository/Research Match
Queries
Call
Center/Prescreening/Scheduling
Cost Sharing for Advertising
33.3   Indicate community engaging assistance requested and/or received in the development of the study:
Community Engagement
Requested
Received
PHI Statement/Engaging
Stakeholders Section
CEnR Navigation – fostering
pt/community partnership
Outreach to
community/partner/advocacy
group/CE Studio
33.4   Indicate other assistance requested and/or received in the development of the study:
Other
Requested
Received
Survey design, fielding,
validation
Data transfer and security
planning
34.0
BERD: Biostatistics, Epidemiology and Research Design
Resource
34.1   Indicate the Biostatistical assistance requested and/or received in the development of this
study:
Requested
Received
Development of experimental
design
Power analysis/Sample size
determination (# of subjects)
Navigation (Did Statistician
participate in a navigation
meeting)
Randomization schedule

Data analysis
Development of new
statistical techniques for data
analysis (Statistical research)
Protocol implementation
Other
34.2   If you are/will be using data analysis specify:
Exploratory
Descriptive
Hypothesis testing
Statistical modeling
Other
34.3   If you are/will be assisted with protocol implementation, specify:
Publication
Conference
Other (type of dissemination)
Grant(s)
34.4   Please select the Biostatistician on this Protocol:
Roger Vaughan, DrPH
Caroline Jiang, MS
Sandra Garcet, PhD
Adam Qureshi, MA
Other
35.0
Biomedical Informatics Resources
35.1   Indicate Bioinformatics assistance requested and/or received in the development of this study:
Requested
Received
Microarray analysis
Pathway analysis
RNA-seq analysis
Bioinformatics training and
consultation
Bioinformatics experimental
design
HPC computing
Other
35.2   If you are/will be using pathway analysis software, specify:

Ingenuity IPA
David
GSEA
Other
35.3   If you are/will be using RNAseq analysis software, specify:
Tophat
Cufflinks
Cuffdiff
CummRbund
STAR
featureCounts
DESeq2
VOOM
RNA-SeQC
If other, specify:
35.4  
Indicate Medical Informatics assistance requested and/or received in the development of this study:
Requested
Received
Data storage inside of iRIS
Redcap Database
Custom or Ad Hoc reports
Study plan creation
Specialize database or
custom software
Other
36.0
HIPAA Form
36.1   A study's specific HIPAA form signed by the volunteer is required for institutions that are HIPAA
covered entities so that they may communicate Private Health Information (PHI) to the Investigator.  
Below, Memorial Sloan Kettering Cancer Center, New York-Presbyterian Hospital and Weill Medical
College of Cornell University are listed so that that they may report laboratory results and X-ray
readings respectively.  If you foresee that any other entity may need to provide PHI then add them to
the field highlighted in green.
36.2   Name of Study:     
Identification of thermogenic silencing regulatory factors as biomarkers of metabolic health in humans
36.3   Principal Investigator:
Paul Cohen, MD, PhD
36.4   Industry Sponsor:
If the funding source is industry please type in the sponsor here
Who may obtain, use, and/or disclose your health information?

The following persons and organizations may obtain, use, or disclose health information about you.
The Principal Investigator(s) listed at the top of this form, and persons who assist the
Investigator(s) in carrying out the research
Each research site for this study, including The Rockefeller University, and the research
management and support staff and the medical staff at each site
Health care providers who have provided in the past, or currently provide, health care services
to you
Laboratories and other persons and organizations that will analyze your health information
and/or biological samples as part of this study, including Memorial Sloan Kettering Cancer
Center, New York-Presbyterian Hospital and Weill Medical College of Cornell University
Other entities that may need to provide PHI:
Cornell University- Ithaca, NY 
Members and staff of the Institutional Review Board and other boards and committees that
watch over research at The Rockefeller University 
Members and staff of The Rockefeller University's Office of Sponsored Research
The sponsor(s) of the research, named above, and persons who watch over the research for the
sponsor(s)
The United States Food and Drug Administration, other government agencies, regulatory entities
and Rockefeller University consultants that watch over the safety, effectiveness, and quality of
research and/or fund The Rockefeller University Hospital
Others (as described here):
What information will be obtained, used, or disclosed?   
The persons and organizations listed above may obtain, use, and disclose:  
Information about you that is created or collected during the research study (but not including
any HIV-related information) 
Health information in your medical records that is relevant to the research study (but not
including any HIV-related information)
And, if checked below:
 
___ HIV-related information (this includes any information indicating that you have had an HIV-
related test or have HIV infection, HIV-related illness, or AIDS, as well as information that could
indicate you may have been exposed to HIV) 
___ Other information (as described here):
                                                                                                                                              
                                                                                                                                              
                                                                                                                                              
                                                                                                                                               
Other information (as described here):
 
By signing this form, you give permission to the persons and organizations listed above to obtain, use
and disclose your health information noted above. 
 
 
How will your health information be used?
 
The health information noted above, as well as information shown by the boxes checked above (if
any), may be obtained, used, and disclosed: 
to conduct the research study explained to you during the informed consent process; and
to assure the quality, safety, and effectiveness of the research study 
 
Please note that the persons and organizations listed above may re-use or further disclose your
information if they are permitted by law to do so.
 
 
What are your rights?
 
It is your right to refuse to sign this authorization form.  If you do not sign this form, you will not be
able to participate in the research study.  Your health care outside the study will not be affected.  The
payment for your health care and your health care benefits will not be affected.
If you sign this authorization form, you will have the right to withdraw it at any time except to the
extent that the persons and organizations listed above:
have already taken action based upon your authorization;
need the previously collected information to complete analysis and reports of data for this
research; or
will continue to use and disclose previously collected information as permitted by the informed
consent form signed by you (except as to HIV-related information, for which disclosure to new
persons or organizations will not occur unless permitted by federal or state law). 
If you withdraw the authorization, you will not be permitted to continue taking part in the research
study.  This authorization form will not expire unless you withdraw it.  If you want to withdraw this
authorization, please write to the above named investigators. 
You have a right to see and copy your health information described in this authorization form in
accordance with The Rockefeller University's policies; in certain circumstances where the integrity of
the study will be affected, you will not be able to obtain your health records in this study until the
study has been completed.
You will receive a copy of this form after you have signed it.
 
 
Notice Concerning HIV-Related Information

If you are authorizing the release of HIV-related information, you should be aware that such
information may not be shared without your approval unless permitted by federal or state law.  You
also have a right to request a list of people who may receive or use your HIV-related information
without authorization.  If you experience discrimination because of the release or disclosure of HIV-
related information, you may contact the New York State Division of Human Rights at (212) 480-
2493 or the New York City Commission of Human Rights at (212) 306-7450.  These agencies are
responsible for protecting your rights.
 
Your signature
I have read this form, and all of my questions have been answered.  By signing below, I acknowledge
that I have read and accept all of the information above.
 
 
 
                                                           
Signature of participant or participant's legal
representative
 
                                                           
Printed name of participant
 
 
 
 
                                                           
Date
 
 
________________________________
Printed name of legal representative (if applicable)
 
 
                                    ___________
Representative's relationship to participant
 
 
 
 
 
 
THE STUDY PARTICIPANT OR HIS OR HER PERSONAL REPRESENTATIVE MUST BE PROVIDED WITH A
COPY OF THIS FORM AFTER IT HAS BEEN SIGNED.
 
37.0
End of Application Form
37.1   The study application form is complete.   
The next step in the submission  process is to gather attachments before proceeding to the
submission form. 
 
The following submission reports are generated in the Lab/Dept Reports menu, Submission Reports
section:
   - Delegation of Authority (if applicable, and if not previously generated)
   - HIPAA form (if applicable)
   - CCTS Utilization Report (required for all submissions)
   - Study Progress Report  (if the study has been managed in iRIS for a minimum of one year,
generate the Progress Report from the report menu in iRIS.  if the study has not been managed in iRIS
for one year, complete the Progress Report located on the IRB website.)
 
All other required forms can be downloaded from the corresponding sections' help links above or from the IRB
website.