Exenatide and Brown Adipose Tissue

NCT03002675 | Unknown Phase 4 DMC

• 1 other identifier: P16.078
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

The obesity epidemic has led to a enormous increase in the prevalence of type 2 diabetes mellitus (T2D), dyslipidemia and cardiovascular events. Particularly South Asians, who comprise 1/5 of the world population, are at increased risk of developing a disadvantageous metabolic phenotype and these diseases. Moreover, T2D occurs at a younger age and at a lower BMI when compared to white Caucasians. Recent research has shown that South Asians not only have a lower energy expenditure than their Caucasian counterparts, but also less active brown adipose tissue (BAT). For some time, it has been known that adult humans have active BAT. This metabolic tissue produces heat by combusting triglycerides, in contrast to white adipose tissue, which stores this form of energy. It has been shown that activation of BAT has a positive effect on whole body metabolism, via increasing energy expenditure and improving glucose- and lipid metabolism. For this matter, BAT has been proposed as a major key player in energy homeostasis, which may be implemented in the current combat against the obesity epidemic. Aside from cold exposure, more research focuses on pharmacological activation of BAT. Glucagon-like peptide 1 (GLP-1) is an incretin hormone which is produced by intestinal L-cells and upon food intake stimulates insulin secretion by pancreatic beta cells. The GLP-1 analogue Exenatide is a currently much used antidiabetic drug to reduce hyperglycemia via this aforementioned mechanism. Beyond its blood glucose-improving effects, Exenatide has also shown to lower body weight and improve dyslipidemia in T2D patients. Elucidation of the underlying mechanism of these beneficial effects is highly relevant. Recent preclinical research in our group has shown that central activation of the GLP-1 receptor through exenatide increases BAT activity and thereby contributes to weight loss and improvement of dyslipidemia. The aim of this research project is to investigate whether exenatide is also able to activate BAT and increase resting energy expenditure, thereby improving glucose- and lipid metabolism and reducing fat mass and body weight in humans. Moreover, the investigators aim to validate the MRI scan as a novel way to measure BAT activity. The investigators hope that these forthcoming findings lead to the discovery of new treatment strategies against obesity.

Conditions

Obesity

Keywords

Adipose tissue; Type 2 diabetes

Outcome Measures

Primary Outcomes (1)

• The effect of exenatide on BAT activity and energy expenditure in healthy young South Asian compared to white Caucasian men

  End of the study, up to 21 months

Secondary Outcomes (1)

• Visualisation of BAT as measured with MRI scan compared to FDG-PET CT

  End of the study, up to 21 months

Study Arms (1)

exenatide

EXPERIMENTAL

Participants will receive exenatide (Bydureon, 2mg s.c. 1x/wk, AstraZeneca) during 12 weeks

Drug: Bydureon

Interventions

Bydureon DRUG

exenatide (Bydureon) 2mg s.c. 1x/wk

Also known as: exenatide

exenatide

Eligibility Criteria

• Age: 20 Years - 30 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Dutch South Asian or white Caucasian male, 20-30 years
• BMI ≥ 18 and ≤ 25 kg/m2
• Good general health

You may not qualify if:

• BMI \> 25 kg/m2 or \< 18 kg/m2
• Use of medication known to influence glucose and/or lipid metabolism or brown fat activity (e.g. beta blockers)
• Any significant chronic disease
• Renal, hepatic or endocrine disease
• Smoking
• Participation in an intensive weight-loss program or vigorous exercise program during the last year before the start of the study
• Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year
• Contraindications for undergoing an MRI scan:
• Presence of non-MR safe metal implants or objects in the body.
• Pacemaker, neurostimulator, hydrocephalus pump, drug pump, non-removable hearing aid, large recent tattoos.
• Claustrophobia
• Tinnitus or hyperacusis

Sponsors & Collaborators

• Ingrid Jazet: lead
• AstraZeneca: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, South Holland, 2333 ZA, Netherlands

RECRUITING

Related Publications (1)

• Janssen LGM, Nahon KJ, Bracke KFM, van den Broek D, Smit R, Sardjoe Mishre ASD, Koorneef LL, Martinez-Tellez B, Burakiewicz J, Kan HE, van Velden FHP, Pereira Arias-Bouda LM, de Geus-Oei LF, Berbee JFP, Jazet IM, Boon MR, Rensen PCN. Twelve weeks of exenatide treatment increases [18F]fluorodeoxyglucose uptake by brown adipose tissue without affecting oxidative resting energy expenditure in nondiabetic males. Metabolism. 2020 May;106:154167. doi: 10.1016/j.metabol.2020.154167. Epub 2020 Jan 23.

  PMID: 31982480 DERIVED

MeSH Terms

Conditions

Obesity; Diabetes Mellitus, Type 2

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Study Officials

• Ingrid Jazet, MD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ingrid Jazet Jazet, MD

CONTACT

i.m.jazet@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: December 15, 2016
• First Posted: December 26, 2016
• Study Start: August 1, 2016
• Primary Completion: June 1, 2018
• Last Updated: December 26, 2016

Record last verified: 2016-12

Locations

NL (1)