Brown Adipose Tissue Activity in Response to Semaglutide Administered to Obese Subjects.

Obesity Clinical Trial

Official title:

Brown Adipose Tissue Activity in Response to Semaglutide Administered to Obese Subjects.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05419726
• Other study ID #: 22-000718
• Status: Recruiting
• Start date: February 1, 2023
• Est. completion date: June 1, 2025

Study information

• Verified date: March 2024
• Source: University of California, Los Angeles
• Contact: Preethi Srikanthan, MD
• Phone: 310-825-7922
• Email: psrikanthan[@]mednet.ucla.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Glucagon like peptide (GLP-1) agonists, such as liraglutide, exenatide, and semaglutide, have been increasingly used as a medication to address the current twin epidemics of diabetes and obesity. Their activities include increasing insulin production by pancreatic beta cells, improving insulin sensitivity in muscles and weight loss. The mechanisms underpinning the weight loss caused by GLP-1 agonists have not yet been fully elucidated, but brown adipose tissue (BAT) appears to play an important role.

We propose to assess BAT activity, using infrared thermography camera images, before individuals start weekly administration of semaglutide, at week 2-4, and week 18-20. We hypothesize that this GLP-1 agonist, semaglutide, will cause an increase in BAT activity and a corresponding increase in basal metabolic rate.

Description:

Background and Rationale:

Glucagon like peptide (GLP-1) agonists, such as liraglutide, exenatide, and semaglutide, have been increasingly used as a medication to address the current twin epidemics of diabetes and obesity. Their activities include increasing insulin production by pancreatic beta cells, improving insulin sensitivity in muscles and weight loss. The mechanisms underpinning the weight loss caused by GLP-1 agonists have not yet been fully elucidated, but brown adipose tissue (BAT) appears to play an important role.

BAT is a type of adipose tissue which predominates in infants to allow thermoregulation through adaptive thermogenesis, but it is also present in adults. BAT activity also increases insulin sensitivity and whole body energy expenditure, and thus has the potential to treat type 2 diabetes and obesity. Bilateral supraclavicular and axillary BAT account for approximately two thirds of total body BAT content. Although the precise role of BAT in human metabolism and energy balance is unknown, a clear link exists between obesity and BAT dysfunction in humans.

It has been hypothesized that the prominent weight loss activity of GLP-1 agonists in humans is the result of BAT activation. However, studies with various GLP-1 agonists have been equivocal.

With more powerful GLP-1 agonists such as semaglutide entering in clinical practice, a better understanding of the relationship between GLP-1 and BAT is important. If BAT activity is found to be clinically significant as a mechanism of action of GLP-1 agonists, then the addition of adjuvants which enhance BAT activity could optimize the benefit of these medications.

Currently, the main methods available to assess BAT activity are PET-CT with 18F-fluorodeoxyglucose, single-photon-emission CT scanning with tracers such as 123 I-meta-iodobenzylguanidine or 99mTc-tetrofosmin, and/or tissue biopsy 17-19.These techniques have distinct disadvantages as they are expensive and require either the administration of radiopharmaceuticals or tissue sampling. Their utility is, therefore, greatly limited as they can only be conducted on a very small number of subjects and are unable to provide indices of BAT function in real-time. Symonds et al demonstrated the feasibility of using infrared thermography as a safe, reproducible, and robust technique for measuring the temperature of the skin overlying BAT depots in the supraclavicular region and quantifying BAT thermogenesis induced by a cold challenge.

We propose to assess BAT activity, using infrared thermography camera images, before individuals start weekly administration of semaglutide, at week 2- 4, and week 18-20. We hypothesize that this GLP-1 agonist, semaglutide, will cause an increase in BAT activity and a corresponsing increase in basal metabolic rate.

Utilizing a reproducible and non invasive measure of BAT activity, we hope to gain better understanding of BAT activity in concert with the metabolic status of patients commenced on semaglutide. This will not only allow insights into the mechanism of achieving weight loss with semaglutide, it will also allow better understanding of the importance of BAT activity manipulation in the therapy for obesity.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 1, 2025
• Est. primary completion date: January 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subjects scheduled to start semaglutide for weight loss (drug not provided by or paid for by the study)

• >18 years of age and willing to participate

• Male or post-menopausal females

Exclusion Criteria:

• History of prior neck surgery and /or neck irradiation

• Use of beta blocker agents

• Use of any other glucose lowering medication

• History of neuropathic disorders (e.g. diabetic neuropathy)

• Diabetic patients

• Individuals without normal thyroid function

• Individuals with cancer

• Any significant chronic disease or renal, hepatic or endocrine disease

• Current smokers

• Inability of patient to provide consent either for medical reasons or psychiatric reasons

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Semaglutide Injectable Product (not provided by the study)
Study Procedure: Subjects that are to be started on semaglutide by their physician will be invited to participate in the study. If the subject is eligible and signs the consent form they will be enrolled in the study. There are three (3) study visits including Baseline/Visit 1 (prior to starting semaglutide), Visit 2 (at week 2-4) and Visit 3 (at week 18-20). The subjects undergo these tests at each visit: weight circumference measured, BMR testing, thermal imaging of BAT, and perform a 24 hour food recall.

Locations

Country	Name	City	State
United States	UCLA Health	Los Angeles	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, Los Angeles

Country where clinical trial is conducted

United States, 

References & Publications (20)

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* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in supraclavicular temperature with cold exposure	delta temperature	20weeks
Primary	change in caloric intake	caloric intake	20weeks
Primary	basal metabolic rate	basal metabolic rate (ml O2/min or joule per hour per kg body mass)	20 weeks