Clinical trial NCT04357964: Beige Fat, Energy, and the Natriuretic Peptide System
Official title: Beige Fat, Energy, and the Natriuretic Peptide System (ENDA-025-17S)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Obesity
Keywords: adipose tissue
beige adipose tissue
cardiovascular physiology
B-type natriuretic peptide
metabolism
obesity
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
Collaborators: name: Vanderbilt University Medical Center
First posted: 2020-04-22
Enrollment: 137
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Healthy volunteers who are U.S. veterans

Brief summary: Obese individuals experience an increased risk of cardiovascular and metabolic diseases. Evidence from genetic studies indicate that the natriuretic peptide (NP) system may protect against these diseases. NP levels differ by obesity status and race has not been established in humans. Thus, the investigators propose a study in which will quantify adipose tissue gene expression and energy expenditure in states of NP deficiency in humans. The overarching postulate is that obese and black individuals have NP deficiencies that contribute to less beige adipose tissue and lower energy expenditure.

Detailed description: Obesity represents a serious public health burden. Obese individuals experience increased risk of cardiovascular and metabolic cardiometabolic disease, including insulin diabetes, resistance, hypertension, and dyslipidemia. Obesity and obesity-associated cardiometabolic dysfunction are significant contributors to morbidity and mortality in Veterans. This indicates that obesity and cardiometabolic dysfunction are complex and multifactorial, and suggests that there are additional factors that contribute to the pathogenesis of obesity and its associated cardiometabolic risk that have been discovered. Moreover, some of the pharmacologic therapies for obesity can have adverse cardiovascular effects. Thus, it is crucial to improve the understanding of the multiple pathways contributing to the pathogenesis of obesity and obesity-associated cardiometabolic risk, including the identification of novel relevant pathways, in order to develop more effective treatments for these diseases. The proposed work will form a foundation for future high-impact studies of mechanisms for adiposity and cardiometabolic disease.

Eligibility criteria: Inclusion Criteria:

* Men and women ages 18-55 years
* Body Mass Index (BMI) \>= 18.5 and \<25 kg/m2 (lean), or BMI 30 kg/m2 (obese)

Exclusion Criteria:

* Significant pulmonary, liver, or renal disease
* Heart failure (any type) or unstable coronary artery disease
* Diabetes Mellitus (Types 1 and 2)
* Thyroid dysfunction
* Active malignancy
* Chronic inflammatory diseases, such as inflammatory bowel disease, hepatitis, rheumatoid arthritis
* Current use of medications likely to affect energy homeostasis, including glucocorticoids, amphetamines, and beta blockers
* Currently pregnant or breastfeeding, or unwilling to avoid becoming pregnant or breastfeeding during study duration
* Significant claustrophobia that would prevent the use of the metabolic cart as part of the study protocol
* Hemoglobin A1c (HbA1c) \>= 6.5%
* Liver Function Tests (LFTs) elevated \>3x upper limit of normal
* Estimated Glomerular Filtration Rate (eGFR) \<40 ml/min
* Currently abnormal thyroid stimulating hormone (TSH)

Primary outcomes:
measure: Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Obesity Status
timeFrame: Study Day 1
Secondary outcomes:
measure: Associations of Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1) With Natriuretic Peptide Markers
timeFrame: Study Day 1
measure: Adipose Tissue Gene Expression of UCP1 (Uncoupling Protein 1)- Differences by Race
timeFrame: Study Day 1
Other outcomes:
Locations:
city: Nashville
country: United States
facility: VA TVHS Nashville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
affiliation: Tennessee Valley Healthcare System Nashville Campus, Nashville, TN
name: Alp Ikizler, MD
role: PRINCIPAL_INVESTIGATOR
References: