Abdominal Obesity, Cardiovascular Inflammation, and Effects of Growth Hormone Releasing Hormone Analogue

NCT01632592 | Withdrawn DMC

• 1 other identifier: 2012p-000917
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity is strongly associated with risk of cardiovascular disease (CVD). Data increasingly suggest that visceral adipose tissue (VAT) accumulation -- or increased abdominal fat -- is particularly deleterious to cardiovascular health, but further study is needed to test this idea. Increased abdominal fat may also be associated with lower secretion of a hormone called growth hormone (GH), which helps the body burn fat. The current study aims to carefully characterize relationships between abdominal fat and CVD. In addition, by using a medication called growth hormone releasing hormone, which is a strategy to reduce abdominal fat, the investigators will test the hypothesis that abdominal fat contributes uniquely to increased arterial inflammation. In the first part of this study, the investigators will investigate both lean (healthy weight) individuals and individuals with increased abdominal fat. The investigators will study their body composition, cardiovascular risk measures, insulin sensitivity, and growth hormone dynamics, with the hypothesis that abdominal fat, independent of general obesity, will be strongly associated with arterial wall thickening and atherosclerotic inflammation. The investigators will assess arterial wall thickness, plaque morphology, and atherosclerotic inflammation, and the investigators will determine associations between these variables and regional fat accumulation, with particular attention to abdominal fat. The second, treatment part of the study will be only for individuals with increased abdominal fat who are found to have low growth hormone secretion. In that part of the study, the investigators will test the effects of a growth hormone releasing hormone (GHRH) analogue to reduce abdominal fat and, consequently, reduce arterial inflammation. The investigators hypothesize that abdominal fat reduction, independent of changes in growth hormone, will reduce arterial inflammation and arterial wall thickness.

Conditions

Abdominal Obesity

Outcome Measures

Primary Outcomes (1)

• aortic "target to background ratio" (Aortic TBR)

  aortic target-to-background ratio is a measure of the inflammation in the wall of the aorta that is made by positron emission tomography (PET) scanning in conjunction with computed tomography (CT) scanning.

  12 months

Study Arms (2)

Growth Hormone Releasing Hormone

EXPERIMENTAL

Growth Hormone Releasing Hormone analogue, 2mg subcutaneously every day for 12 months.

Drug: Tesamorelin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Tesamorelin DRUG

The Growth Hormone Releasing Hormone analogue tesamorelin, 2mg subcutaneously daily by injection

Growth Hormone Releasing Hormone

Placebo DRUG

placebo given by injection 2mg subcutaneously daily

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Men and women age 18-55y
• BMI \> 18.5 and \< 25 kg/m2
• Waist circumference \< 102 cm in men and \<88cm in women
• Men and women age 18-55y
• BMI ≥ 30kg/m2
• Abdominal obesity as defined by waist circumference ≥ 102 cm in men and ≥ 88 cm in women
• Relative GH deficiency as demonstrated by peak GH to arginine/GHRH stimulation test of \< 9mcg/L (for treatment portion only)
• Negative age-appropriate screening for cancer performed by primary care physician (e.g., negative mammogram if F \> 50yo) (For treatment portion only)
• Obesity due to known secondary causes
• Use of weight-lowering drugs or previous weight loss surgery
• Use of gonadal steroids, GH, GHRH, glucocorticoids, megesterol acetate, antidiabetic agents, or any other hormonal medication judged by the investigator to be inappropriate within the past 6 months. Use of physiologic testosterone replacement will be allowed.
• Statin use
• Known coronary artery disease or peripheral vascular disease, or any history of stroke or significant chest pain
• Known auto-immune or inflammatory disease
• Any surgery or significant injury (including fracture or other trauma) within the past 6 months

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Obesity, Abdominal

Interventions

tesamorelin

Condition Hierarchy (Ancestors)

Obesity; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Steven Grinspoon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine, Harvard Medical School

Study Record Dates

• First Submitted: June 27, 2012
• First Posted: July 3, 2012
• Study Start: January 1, 2014
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: January 24, 2014

Record last verified: 2014-01

Locations

US (1)