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

This study is not yet open for participant recruitment.
Verified March 2013 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01632592
First received: June 27, 2012
Last updated: March 22, 2013
Last verified: March 2013
History of Changes
  Purpose

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.


Condition Intervention
Abdominal Obesity
 Drug: Tesamorelin
Drug: Placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Abdominal Obesity, Cardiovascular Inflammation, and Effects of a Growth Hormone Releasing Hormone Analogue to Reduce Inflammation

Resource links provided by NLM:

MedlinePlus related topics: Obesity
U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • aortic "target to background ratio" (Aortic TBR) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 160
Study Start Date: January 2014
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: June 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Growth Hormone Releasing Hormone
Growth Hormone Releasing Hormone analogue, 2mg subcutaneously every day for 12 months.
 Drug: Tesamorelin
The Growth Hormone Releasing Hormone analogue tesamorelin, 2mg subcutaneously daily by injection
Placebo Comparator: Placebo Drug: Placebo
placebo given by injection 2mg subcutaneously daily

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion/Exclusion Criteria:

Inclusion Criteria for Lean Controls:

  1. Men and women age 18-55y
  2. BMI > 18.5 and < 25 kg/m2
  3. Waist circumference < 102 cm in men and <88cm in women

Inclusion criteria for Abdominal Obesity:

  1. Men and women age 18-55y
  2. BMI ≥ 30kg/m2
  3. Abdominal obesity as defined by waist circumference ≥ 102 cm in men and ≥ 88 cm in women
  4. Relative GH deficiency as demonstrated by peak GH to arginine/GHRH stimulation test of < 9mcg/L (for treatment portion only)
  5. Negative age-appropriate screening for cancer performed by primary care physician (e.g., negative mammogram if F > 50yo) (For treatment portion only)

Exclusion criteria for all subjects:

  1. Obesity due to known secondary causes
  2. Use of weight-lowering drugs or previous weight loss surgery
  3. 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.
  4. Statin use
  5. Known coronary artery disease or peripheral vascular disease, or any history of stroke or significant chest pain
  6. Known auto-immune or inflammatory disease
  7. Any surgery or significant injury (including fracture or other trauma) within the past 6 months
  8. Hemoglobin < 11g/dL, fasting glucose > 126mg/dL, creatinine <1.5mg/dL, or AST > 2.5x upper limit of normal
  9. FSH > 20 IU/L (women only)
  10. Positive urine pregnancy test, actively seeking pregnancy, or breastfeeding
  11. Prior history of pituitary disease, pituitary surgery, or head irradiation, or any other condition known to affect pituitary function
  12. Infectious illness in the past 3 months, or chronic infectious illness
  13. Allergy to iodine containing contrast media
  14. Active illicit drug use
  15. For women of childbearing potential, failure to use an acceptable form of non-hormonal birth control
  16. Active malignancy: For the treatment part of the study, all active malignancy will be excluded. For the observational part of the study (which involves no intervention) basal cell carcinoma and low grade cervical or anal intraepithelial neoplasms will be allowed.
  17. History of colon cancer (treatment part only)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01632592

Contacts
Contact: Steven Grinspoon, MD 617-724-9109 sgrinspoon@partners.org

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Steven Grinspoon, MD Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Steven K. Grinspoon, MD, Professor of Medicine, Harvard Medical School, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01632592     History of Changes
Other Study ID Numbers: 2012p-000917
Study First Received: June 27, 2012
Last Updated: March 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Inflammation
Obesity
Obesity, Abdominal
Pathologic Processes
Overnutrition
Nutrition Disorders
Overweight
 Body Weight
Signs and Symptoms
Hormones
Growth Hormone-Releasing Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on May 16, 2013