ObesitymTORHBFCNCT04206124
mTORC1 and Autophagy in Human Brown Adipocytes
A study testing Brown Fat Harvest During Anterior Neck Surgery in people with Obesity and Metabolic Disease, run by University of New Mexico at 1 site in United States.
Trial summary
The long term goal is to identify the potential therapeutic targets for the treatment of obesity and its associated disorders by studying the driving factors of activation of brown adipose tissue (BAT) in human adults. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Metabolic Disease
- What is being tested?
- Brown Fat Harvest During Anterior Neck Surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2016to 30 Sep 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Male or Female
- age 18-60
- able to give informed consent
- non-diabetic
- scheduled for anterior cervical spine, thyroidectomy, or parathyroidectomy surgery at UNMHSC
- BMI <25 (lean) or >30 (obese)
- English or Spanish speaking
Who cannot join
- has diabetes mellitus (type I or II)
- currently on any study medication (including sedatives or analgesics, coagulopathy (INR of 1.5 or greater, platelet count of <50,000/microliter), or anticoagulant)
- pregnant
- incarcerated
Trial locations and contacts
1 site in 1 country.
United States1 site
University of New Mexico Health Sciences Center
Albuquerque, New Mexico, 87131
About this study
Official title: Regulation of Beige Fat Development by mTORC1 and Autophagy
The long term goal is to identify the potential therapeutic targets for the treatment of obesity and its associated disorders by studying the driving factors of activation of brown adipose tissue (BAT) in human adults. Whereas activation of brown adipose tissue (BAT) in human adults has been considered as a potential therapeutic target to battle obesity since it was identified in 2009, the underlying mechanisms of beige adipocytes appearance in human adults is unclear. The objective of this proposal is to investigate the role of autophagy in mediating the inhibitory effect of mammalian target of rapamycin complex 1 (mTORC1) in regulating human brown adipocytes. The central hypothesis is that autophagy plays a critical role in regulating browning of white adipose tissue and mediates the beneficial effect of mTORC1 inhibition on thermogenesis in human brown adipocytes.
Read the detailed description
Specific Aim 1: To investigate the role of mTORC1 and autophagy in regulating thermogenesis in human brown adipocytes. The working hypothesis is that inhibition of mTORC1 or activation of autophagy improves thermogenesis in human brown adipocytes. It will be first determined if the mTORC1/autophagy signaling modulates thermogenic gene expression and beige markers by collecting human brown fat from lean non-diabetic subjects. The brown fat during the anterior cervical spine surgery or thyroidectomy from lean subjects with a BMI <25, or obese participants who have a BMI >30, will be harvested and then be used to determine: 1) whether mTORC1 signaling, autophagy and thermogenic gene expression, and the fraction of various types of immune cells in human brown fat are different from those in rodents;2) whether rapamycin treatment enhances basal or CL-induced thermogenic gene expression and O2 consumption in primary human brown adipocytes; and 3) whether inhibition of autophagy by 3-methyladenine (3-MA) suppresses thermogenic gene expression induced by CL316,243, a β3-adrenoceptor agonist that mimics cold stress in vivo in human brown adipocytes.
Overall, this study will lead to the identification of mTORC1 as a key regulator of thermogenesis in human adipose tissue and reveal promising new anti-obesity drug targets. In addition, this study will further investigate the role of rapamycin administration in obesity in human adults near the future. These studies are designed to be a proof-of-principle. If the results are promising, then future drug development could focus on designing new inhibitors of mTORC1.
- Conditions
- Obesity, Metabolic Disease
- Being tested
- Brown Fat Harvest During Anterior Neck Surgery
- Keywords
- Autophagy, Inflammation, Metabolism, Adipocyte, mTORC1, Obesity, Thermogenesis
- Medical subject headings
- Obesity, Metabolic Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Brown Fat Harvest During Anterior Neck SurgeryProcedure or surgery
During previously indicated thyroid gland removal or anterior cervical spine surgery, as scheduled at UNMHSC, the surgeon will identify the large muscle on the side of the neck in the surgical field. Using minimal dissection adjacent to the muscle, they will then remove 5-10mg of brown fat from this region. These samples will be further analyzed using various biochemical tools.
| Study group | Role | What they receive |
|---|---|---|
| Single Arm Study Group | Experimental | Includes all consented patients, male and female, undergoing anterior cervical spine surgery, parathyroidectomy or thyroidectomy (18-60 years old), without history of diabetes mellitus and not pregnant or incarcerated. Receives: Procedure: Brown Fat Harvest During Anterior Neck Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Protein expression levels in lean and obese human brown adipose tissue samples will be quantified via Western Blot and comparatively analyzed using a student T-test.
Human brown adipose tissue (BAT) samples will be collected during previously scheduled anterior neck surgery and then cultured and amplified for experiments including Western Blot (WB), an assay to quantify the relative amounts of protein present in a sample.
WB will be used to determine how protein expression levels differ between lean and obese BAT samples. Specifically, the translational levels of key markers of mTOR signaling including UCP1, C/EBPβ, HSL, S6K, ADPN, PKA, AMPK and ATGL will be quantified by WB and analyzed statistically using student T-test, and protein activation levels will be quantified by dividing phosphorylated protein content by total protein content.
Measured: Up to six years after date of sample collection.
Gene transcript expression levels in lean and obese human brown adipose tissue samples will be quantified via quantitative Polymerase Chain Reaction and comparatively analyzed using a student T-test.
Human brown adipose tissue (BAT) samples will be collected during previously scheduled anterior neck surgery and then cultured and amplified for experiments including quantitative-Polymerase Chain Reaction (q-PCR), an assay to quantify the relative amounts of mRNA (transcribed genes) present in a sample.
q-PCR will be used to determine how gene expression levels differ between lean and obese BAT samples. Specifically, the transcriptional levels of key markers of mTOR signaling including UCP1, C/EBPβ, HSL, S6K, ADPN, PKA, AMPK and ATGL will be quantified by q-PCR and analyzed using student T-test.
Measured: Up to six years after date of sample collection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Dec 2019
- Study start1 Nov 2016
- Primary completion30 Sep 2020
- Study completion30 Sep 2020
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
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Patients will be recruited based on sex, age, and medical history including BMI (lean, \<25, or obese, \>30), medication list, and health status. Included patients indicated for thyroidectomy, parathyroidectomy, or cervical spine injury surgery, who are able to consent, will have a soybean-sized amount of brown fat removed from the neck during surgery. These tissue samples will be further analyzed using biochemical tools after being de-identified from patient records.
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of New Mexico
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Meilian Liu, University of New Mexico
- Investigators
- Meilian Liu, PhD, Principal investigator, University of New Mexico Biochemistry & Molecular Biology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04206124
- Sponsor's protocol ID
- 14-272
- Acronym
- mTORHBFC
- Status last verified
- Oct 2024
- First submitted
- 13 Dec 2019
- Last updated
- 22 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Participant data will be de-identified after specimen collection. De-identified data will be stored securely and not shared with other researchers.
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Beige Fat Development by mTORC1 and Autophagy
- ClinicalTrials.gov ID
- NCT04206124
- Acronym / sponsor ID
- mTORHBFC / 14-272
- Conditions
- Obesity, Metabolic Disease
- Keywords
- Autophagy, Inflammation, Metabolism, Adipocyte, mTORC1, Obesity, Thermogenesis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- University of New MexicoUniversity, hospital or other
- Study start
- 1 Nov 2016 (actual)
- Primary completion
- 30 Sep 2020 (actual)
- Study completion
- 30 Sep 2020 (actual)
- First posted
- 20 Dec 2019 (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.
The long term goal is to identify the potential therapeutic targets for the treatment of obesity and its associated disorders by studying the driving factors of activation of brown adipose tissue (BAT) in human adults. Whereas activation of brown adipose tissue (BAT) in human adults has been considered as a potential therapeutic target to battle obesity since it was identified in 2009, the underlying mechanisms of beige adipocytes appearance in human adults is unclear. The objective of this proposal is to investigate the role of autophagy in mediating the inhibitory effect of mammalian target of rapamycin complex 1 (mTORC1) in regulating human brown adipocytes. The central hypothesis is that autophagy plays a critical role in regulating browning of white adipose tissue and mediates the beneficial effect of mTORC1 inhibition on thermogenesis in human brown adipocytes.
Detailed description
Specific Aim 1: To investigate the role of mTORC1 and autophagy in regulating thermogenesis in human brown adipocytes. The working hypothesis is that inhibition of mTORC1 or activation of autophagy improves thermogenesis in human brown adipocytes. It will be first determined if the mTORC1/autophagy signaling modulates thermogenic gene expression and beige markers by collecting human brown fat from lean non-diabetic subjects. The brown fat during the anterior cervical spine surgery or thyroidectomy from lean subjects with a BMI <25, or obese participants who have a BMI >30, will be harvested and then be used to determine: 1) whether mTORC1 signaling, autophagy and thermogenic gene expression, and the fraction of various types of immune cells in human brown fat are different from those in rodents;2) whether rapamycin treatment enhances basal or CL-induced thermogenic gene expression and O2 consumption in primary human brown adipocytes; and 3) whether inhibition of autophagy by 3-methyladenine (3-MA) suppresses thermogenic gene expression induced by CL316,243, a β3-adrenoceptor agonist that mimics cold stress in vivo in human brown adipocytes.
Overall, this study will lead to the identification of mTORC1 as a key regulator of thermogenesis in human adipose tissue and reveal promising new anti-obesity drug targets. In addition, this study will further investigate the role of rapamycin administration in obesity in human adults near the future. These studies are designed to be a proof-of-principle. If the results are promising, then future drug development could focus on designing new inhibitors of mTORC1.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients will be recruited based on sex, age, and medical history including BMI (lean, <25, or obese, >30), medication list, and health status. Included patients indicated for thyroidectomy, parathyroidectomy, or cervical spine injury surgery, who are able to consent, will have a soybean-sized amount of brown fat removed from the neck during surgery. These tissue samples will be further analyzed using biochemical tools after being de-identified from patient records.
| Arm | Type | Receives |
|---|---|---|
| Single Arm Study Group | Experimental | Procedure: Brown Fat Harvest During Anterior Neck SurgeryIncludes all consented patients, male and female, undergoing anterior cervical spine surgery, parathyroidectomy or thyroidectomy (18-60 years old), without history of diabetes mellitus and not pregnant or incarcerated. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Male or Female
- age 18-60
- able to give informed consent
- non-diabetic
- scheduled for anterior cervical spine, thyroidectomy, or parathyroidectomy surgery at UNMHSC
Key exclusion criteria (4 listed)
- has diabetes mellitus (type I or II)
- currently on any study medication (including sedatives or analgesics, coagulopathy (INR of 1.5 or greater, platelet count of <50,000/microliter), or anticoagulant)
- pregnant
- incarcerated
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 |
|---|---|---|
| Brown Fat Harvest During Anterior Neck SurgeryDuring previously indicated thyroid gland removal or anterior cervical spine surgery, as scheduled at UNMHSC, the surgeon will identify the large muscle on the side of the neck in the surgical field. Using minimal dissection adjacent to the muscle, they will then remove 5-10mg of brown fat from this region. These samples will be further analyzed using various biochemical tools. | Procedure or surgery | Single Arm Study Group |
Primary outcome
Protein expression levels in lean and obese human brown adipose tissue samples will be quantified via Western Blot and comparatively analyzed using a student T-test.
Time frame: Up to six years after date of sample collection.
Human brown adipose tissue (BAT) samples will be collected during previously scheduled anterior neck surgery and then cultured and amplified for experiments including Western Blot (WB), an assay to quantify the relative amounts of protein present in a sample. WB will be used to determine how protein expression levels differ between lean and obese BAT samples. Specifically, the translational levels of key markers of mTOR signaling including UCP1, C/EBPβ, HSL, S6K, ADPN, PKA, AMPK and ATGL will be quantified by WB and analyzed statistically using student T-test, and protein activation levels will be quantified by dividing phosphorylated protein content by total protein content.
Gene transcript expression levels in lean and obese human brown adipose tissue samples will be quantified via quantitative Polymerase Chain Reaction and comparatively analyzed using a student T-test.
Time frame: Up to six years after date of sample collection.
Human brown adipose tissue (BAT) samples will be collected during previously scheduled anterior neck surgery and then cultured and amplified for experiments including quantitative-Polymerase Chain Reaction (q-PCR), an assay to quantify the relative amounts of mRNA (transcribed genes) present in a sample. q-PCR will be used to determine how gene expression levels differ between lean and obese BAT samples. Specifically, the transcriptional levels of key markers of mTOR signaling including UCP1, C/EBPβ, HSL, S6K, ADPN, PKA, AMPK and ATGL will be quantified by q-PCR and analyzed using student T-test.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2024.
- Individual participant dataSharing planned: No. Participant data will be de-identified after specimen collection. De-identified data will be stored securely and not shared with other researchers.
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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.
Meilian Liu, PhD principal investigator
University of New Mexico Biochemistry & Molecular Biology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Brown Fat Harvest During Anterior Neck Surgery in people with Obesity and Metabolic Disease, run by University of New Mexico 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 7 inclusion and 4 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: finished, as of the sponsor's last update on 22 Oct 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Protein expression levels in lean and obese human brown adipose tissue samples will be quantified via Western Blot and comparatively analyzed using a student T-test. (time frame: Up to six years after date of sample collection.). The study lists 2 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 22 Oct 2024.