ObesityNCT06424132
Thermogenic Silencer Regulatory Factors in Humans
A study testing Cold Vest Exposure Period, Rewarming Exposure Period and Fasting in people with Obesity and Metabolic Disease, run by Rockefeller University at 1 site in United States.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Metabolic Disease, Cold Exposure
- What is being tested?
- Cold Vest Exposure Period, Rewarming Exposure Period and Fasting
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Aug 2024to 4 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 18 years old and 35
- Lean group: BMI is between 18.5 and 24.9. HgA1c <5.7%
- Obese group: BMI is >30, HgA1c <5.7%
- Obese group with Type II diabetes: BMI is >30, HgA1c is >6.5% If on oral medication for diabetes management, HgA1c may be < 6.5% The following medications are also acceptable: statins, aspirin, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin receptor blockers (ARB).
Who cannot join
- Diabetes type I (self-report)
- Diagnosis of thyroid disease (including goiter, hyperthyroidism, hypothyroidism, thyroiditis)(self-report)
- Diagnosis with cancer including skin cancer (self-report)
- Diagnosis or evidence of Raynaud's Syndrome or systemic sclerosis (self-report)
- A recent diagnosis of Coronavirus Disease 2019 (COVID-19) (last 2 weeks) or hospitalized at the time of diagnosis with COVID-19
- Any vaccine administration within two weeks preceding the study procedure
Show all 13Show fewer
- Currently pregnant
- 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.
- Has consumed nicotine (smoking, inhaling, ingesting) within the last 6 months
- Has used illicit drugs within the last 6 months (marijuana users are eligible unless consumed in the last 30 days).
- 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 the integrity of the data
- Diabetes Type II that is managed by insulin.
- Steroid use in the last 30 days to the exclusions
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Identification of Thermogenic Silencing Regulatory Factors as Biomarkers of Metabolic Health in Humans
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.
Read the detailed description
Obesity and associated metabolic diseases 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 adipose tissue (BAT) 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, this study presents a unique approach, aiming to decipher the mechanisms that govern human brown fat silencing. The study hypothesizes that if the regulatory factors that silence brown fat NST can be defined, 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 unlocking the metabolic benefits of human brown fat and would represent promising treatment opportunities for type 2 diabetes and other obesity-related disorders. Understanding these relationships will allow for precision treatment opportunities for type 2 diabetes in the future.
The overall goal of this study is to unlock the metabolic benefits of human brown fat by defining the regulatory mechanisms that keep BAT in a silenced state. The study will generate the first human secretome (list of secreted proteins in blood) and transcriptome (list of gene transcripts in adipose tissue) 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 the profiling will then be functionally validated in human adipocytes for their role in NST silencing. The study 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, the study will instead interrogate circulating factors in human plasma as a proxy for metabolic health. In addition, the study will also obtain subcutaneous adipose tissue for RNA profiling to identify genes that are upregulated under NST-silenced conditions compared to cold exposure.
- Conditions
- Obesity, Metabolic Disease, Cold Exposure
- Being tested
- Cold Vest Exposure Period, Rewarming Exposure Period, Fasting
- Medical subject headings
- Obesity, Metabolic Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cold Vest Exposure PeriodOther
A cold vest will be placed on the participant which consists of a water-perfused wearable vest, size S-M or M-L with adjustable straps attached to a small 'cooler' reservoir to circulate cold water between the vest and the cooler (Polar Products, Stow, OH- Product link: www.polarproducts.com/polarshop/pc/CoolOR-13-Quart-System-with-Arctic-Chiller-p24757.htm) This product is safe and recommended by experimental guidelines for human BAT studies. Participants will be cold exposed for a period of 3 hours resting in a reclined position engaged in reading and/or digital entertainment of their choice.
Rewarming Exposure PeriodOther
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 30 degrees celsius and asked to return to the resting position of their choice. Participants will then engage in reading and/or digital entertainment for a 3-hour warm exposure period.
FastingOther
Participants will be requested to refrain from food and caloric drinks for 12 hours (starting at 8pm) prior to the study visit. Blood will then be drawn the following morning (between 8 and 9am) 30mins later following a breakfast meal (9:30am- 10am). Participants will be housed in a room with ambient temperature at 25 degrees celsius between the two blood draws.
| Study group | Role | What they receive |
|---|---|---|
| Obese group | Experimental | Body Mass Index (BMI) is > 30, Hemoglobin A1c (HgA1c) <5.7% Receives: Other: Cold Vest Exposure Period; Other: Rewarming Exposure Period; Other: Fasting |
| Lean group | Experimental | Body Mass Index (BMI) is between 18.5 and 24.9. Hemoglobin A1c (HgA1c) <5.7% Receives: Other: Cold Vest Exposure Period; Other: Rewarming Exposure Period; Other: Fasting |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identification of adipose tissue transcriptome
RNA sequencing to measure and identify a list of gene transcripts that are differentially expressed before and after re-warming. A true change is defined as 1.5 fold increase or decrease in gene expression.
Measured: Before and after 3-hour rewarming period.
Identification of cold and warm-regulated proteome.
Proteins will be captured from blood and analyzed via mass spectrometry which generates a list of proteins for each sample. The investigators will compare the mean fold change (true change is greater than 1.5 fold) in protein abundance at the specified study time points.
Measured: Before and after 3 hour cold exposure period and before and after 3 hour rewarming period.
Identification of cold and warm-regulated metabolome.
Metabolites will be captured from blood and analyzed via mass spectrometry which generates a list of metabolites for each sample. The investigators will compare the mean fold change (true change is greater than 1.5 fold) in metabolite abundance at the specified study time points.
Measured: Time frame will be before and after 3 hour cold exposure period as well as before and after 3 hour rewarming period.
Secondary outcomes (4)
Nutritional assessments of individuals correlated to expression patterns of human silencer regulatory factors.
Diet History Questionnaire III (DHQ III) to assess food consumption patterns as it relates to the Dietary Guidelines for Americans.
Measured: Baseline
Body Mass Index (BMI) correlated to expression patterns of human silencer regulatory factors.
BMI is calculated by weight and height measured by anthropometric assessments, using the formula weight in kilograms divided by height in meters squared (kilograms/meter^2).
Measured: Baseline
Fat mass body composition (%) measured by Bod Pod correlated to expression patterns of human silencer regulatory factors.
Bod Pod uses Air Displacement Plethysmography (ADP) to determine body composition, the ratio of fat mass to lean mass. The investigators will measure fat mass composition in units of percentage (%).
Measured: Baseline
Lean Mass body composition (%) measured by Bod Pod correlated to expression patterns of human silencer regulatory factors.
Bod Pod uses Air Displacement Plethysmography (ADP) to determine body composition, the ratio of fat mass to lean mass. The investigators will measure lean mass composition in units of percentage (%).
Measured: Baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2024
- Study start16 Aug 2024
- Primary completion4 Dec 2026 (estimated)
- Study completion4 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- Participants in from the two different study groups (lean and obese) will receive the same intervention: cold environmental exposure followed by a rewarming period
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Rockefeller University
- Sponsor type
- University, hospital or other
- Collaborators
- Cornell University
- Responsible party
- Sponsor
- Investigators
- Joeva Barrow, Ph.D., R.D., Principal investigator, The Rockefeller University and Cornell UniversityPaul Cohen, Ph.D., M.D., Principal investigator, The Rockefeller University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06424132
- Sponsor's protocol ID
- PCO1051
- Status last verified
- Sep 2026
- First submitted
- 10 May 2024
- Last updated
- 14 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of Thermogenic Silencing Regulatory Factors as Biomarkers of Metabolic Health in Humans
- ClinicalTrials.gov ID
- NCT06424132
- Acronym / sponsor ID
- PCO1051
- Conditions
- Obesity, Metabolic Disease, Cold Exposure
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Rockefeller UniversityUniversity, hospital or other
- Collaborators
- Cornell University
- Study start
- 16 Aug 2024 (actual)
- Primary completion
- 4 Dec 2026 (estimated)
- Study completion
- 4 Dec 2026 (estimated)
- First posted
- 21 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Obesity and associated metabolic diseases 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 adipose tissue (BAT) 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, this study presents a unique approach, aiming to decipher the mechanisms that govern human brown fat silencing. The study hypothesizes that if the regulatory factors that silence brown fat NST can be defined, 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 unlocking the metabolic benefits of human brown fat and would represent promising treatment opportunities for type 2 diabetes and other obesity-related disorders. Understanding these relationships will allow for precision treatment opportunities for type 2 diabetes in the future.
The overall goal of this study is to unlock the metabolic benefits of human brown fat by defining the regulatory mechanisms that keep BAT in a silenced state. The study will generate the first human secretome (list of secreted proteins in blood) and transcriptome (list of gene transcripts in adipose tissue) 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 the profiling will then be functionally validated in human adipocytes for their role in NST silencing. The study 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, the study will instead interrogate circulating factors in human plasma as a proxy for metabolic health. In addition, the study will also obtain subcutaneous adipose tissue for RNA profiling to identify genes that are upregulated under NST-silenced conditions compared to cold exposure.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants in from the two different study groups (lean and obese) will receive the same intervention: cold environmental exposure followed by a rewarming period
| Arm | Type | Receives |
|---|---|---|
| Obese group | Experimental | Other: Cold Vest Exposure Period, Other: Rewarming Exposure Period, Other: FastingBody Mass Index (BMI) is > 30, Hemoglobin A1c (HgA1c) <5.7% |
| Lean group | Experimental | Other: Cold Vest Exposure Period, Other: Rewarming Exposure Period, Other: FastingBody Mass Index (BMI) is between 18.5 and 24.9. Hemoglobin A1c (HgA1c) <5.7% |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Age between 18 years old and 35
- Lean group: BMI is between 18.5 and 24.9. HgA1c <5.7%
- Obese group: BMI is >30, HgA1c <5.7%
- Obese group with Type II diabetes: BMI is >30, HgA1c is >6.5% If on oral medication for diabetes management, HgA1c may be < 6.5% The following medications are also acceptable: statins, aspirin, angiotensin-converting enzyme inhibitors (ACEi), and angiotensin receptor blockers (ARB).
Key exclusion criteria (13 listed)
- Diabetes type I (self-report)
- Diagnosis of thyroid disease (including goiter, hyperthyroidism, hypothyroidism, thyroiditis)(self-report)
- Diagnosis with cancer including skin cancer (self-report)
- Diagnosis or evidence of Raynaud's Syndrome or systemic sclerosis (self-report)
- A recent diagnosis of Coronavirus Disease 2019 (COVID-19) (last 2 weeks) or hospitalized at the time of diagnosis with COVID-19
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cold Vest Exposure PeriodA cold vest will be placed on the participant which consists of a water-perfused wearable vest, size S-M or M-L with adjustable straps attached to a small 'cooler' reservoir to circulate cold water between the vest and the cooler (Polar Products, Stow, OH- Product link: www.polarproducts.com/polarshop/pc/CoolOR-13-Quart-System-with-Arctic-Chiller-p24757.htm) This product is safe and recommended by experimental guidelines for human BAT studies. Participants will be cold exposed for a period of 3 hours resting in a reclined position engaged in reading and/or digital entertainment of their choice. | Other | Lean group, Obese group |
| Rewarming Exposure PeriodFollowing 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 30 degrees celsius and asked to return to the resting position of their choice. Participants will then engage in reading and/or digital entertainment for a 3-hour warm exposure period. | Other | Lean group, Obese group |
| FastingParticipants will be requested to refrain from food and caloric drinks for 12 hours (starting at 8pm) prior to the study visit. Blood will then be drawn the following morning (between 8 and 9am) 30mins later following a breakfast meal (9:30am- 10am). Participants will be housed in a room with ambient temperature at 25 degrees celsius between the two blood draws. | Other | Lean group, Obese group |
Primary outcome
Identification of adipose tissue transcriptome
Time frame: Before and after 3-hour rewarming period.
RNA sequencing to measure and identify a list of gene transcripts that are differentially expressed before and after re-warming. A true change is defined as 1.5 fold increase or decrease in gene expression.
Identification of cold and warm-regulated proteome.
Time frame: Before and after 3 hour cold exposure period and before and after 3 hour rewarming period.
Proteins will be captured from blood and analyzed via mass spectrometry which generates a list of proteins for each sample. The investigators will compare the mean fold change (true change is greater than 1.5 fold) in protein abundance at the specified study time points.
Identification of cold and warm-regulated metabolome.
Time frame: Time frame will be before and after 3 hour cold exposure period as well as before and after 3 hour rewarming period.
Metabolites will be captured from blood and analyzed via mass spectrometry which generates a list of metabolites for each sample. The investigators will compare the mean fold change (true change is greater than 1.5 fold) in metabolite abundance at the specified study time points.
4 secondary outcomes
Nutritional assessments of individuals correlated to expression patterns of human silencer regulatory factors.
Time frame: Baseline
Body Mass Index (BMI) correlated to expression patterns of human silencer regulatory factors.
Time frame: Baseline
Fat mass body composition (%) measured by Bod Pod correlated to expression patterns of human silencer regulatory factors.
Time frame: Baseline
Lean Mass body composition (%) measured by Bod Pod correlated to expression patterns of human silencer regulatory factors.
Time frame: Baseline
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joeva Barrow, Ph.D., R.D. principal investigator
The Rockefeller University and Cornell University
Paul Cohen, Ph.D., M.D. principal investigator
The Rockefeller University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cold Vest Exposure Period, Rewarming Exposure Period and Fasting in people with Obesity and Metabolic Disease, run by Rockefeller University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 14 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Identification of adipose tissue transcriptome (time frame: Before and after 3-hour rewarming period.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Sep 2026.