Effects of Growth Hormone Releasing Hormone in HIV

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Steven K. Grinspoon, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01263717
First received: December 16, 2010
Last updated: October 10, 2014
Last verified: October 2014
  Purpose

HIV-infection and its treatment are often associated with an increase in belly fat, as well as abnormal cholesterol and problems metabolizing sugar. People with HIV infection and increased belly fat often have decreased growth hormone (GH) levels. Low GH levels may contribute independently to increased belly fat and to increased cardiovascular risk through effects on sugar metabolism, inflammation, and other mechanisms. Tesamorelin, a growth hormone releasing hormone (GHRH) analogue, has been shown to to reduce belly fat in patients with HIV-associated abdominal fat accumulation. However, the effects of tesamorelin on fat accumulation in the liver and muscle, sugar metabolism, and cardiovascular health are not yet known. The current study is designed to determine the effects of tesamorelin treatment on fat accumulation in the muscle and liver, insulin sensitivity and sugar metabolism, and markers of cardiovascular health including blood vessel thickness (carotid intima media thickness [cIMT]) and markers of inflammation in the body. The investigators hypothesize that tesamorelin will decrease fat accumulation in the liver and muscle and will decrease markers of inflammation, with either neutral or beneficial effects on glucose metabolism.


Condition Intervention
HIV
HIV Lipodystrophy
Drug: tesamorelin
Drug: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Growth Hormone Releasing Hormone on Fat Redistribution, Cardiovascular Indices, and Growth Hormone Secretion in HIV Lipodystrophy

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Liver Fat [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Hepatic fat as measured by magnetic resonance (MR) spectroscopy, and expressed by normalizing lipid to water and expressing as a percent (lipid-to-water percent).

  • Visceral Adipose Tissue [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra.


Secondary Outcome Measures:
  • Intramyocellular Lipid [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Intramyocellular lipid (IMCL) as measured by magnetic resonance (MR) spectroscopy of the calf. Soleus IMCL normalized to creatinine (IMCL/Cr based on areas determined by spectroscopy) was measured. The change over 6 months is reported.

  • Endogenous Growth Hormone Secretion [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given.

  • Insulin Sensitivity [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    In a subgroup of 1/2 of the subjects, euglycemic hyperinsulinemic clamp will be performed to assess insulin-stimulated glucose uptake. Insulin stimulated glucose uptake (M) calculated using the method of DeFronzo is shown.

  • HbA1c [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Hemoglobin A1c.

  • Insulin Like Growth Factor 1 (IGF-I) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Insulin Like Growth Factor 1 (IGF-I).

  • Lipid Panel [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Fasting lipids. Triglyceride value is given.

  • Carotid Intimal Medial Thickness (cIMT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Carotid Intimal Medial Thickness (cIMT).

  • Glucose Tolerance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.

  • Adiponectin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    adiponectin.

  • Hemostatic Markers [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.


Enrollment: 54
Study Start Date: December 2010
Study Completion Date: February 2014
Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tesamorelin
Tesamorelin (growth hormone releasing hormone) 2mg daily given subcutaneously x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose
Drug: tesamorelin
Tesamorelin (growth hormone releasing hormone) 2mg daily given by subcutaneous injection x 6 months during randomized phase, followed by 6 months of open-label tesamorelin at same dose
Other Name: Egrifta, growth hormone releasing hormone, TH9507
Placebo Comparator: Placebo (inactive injection)
Placebo 2mg daily given subcutaneously for the first 6 months of the study, followed by 6 months of tesamorelin (growth hormone releasing hormone) 2mg daily during an open label phase
Drug: placebo
Placebo 2mg daily given by subcutaneous injection for the first 6 months of the study, followed by an open-label phase of 6 months of tesamorelin (growth hormone releasing hormone) treatment, 2mg daily given by subcutaneous injection

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women age 18-65
  2. Previously diagnosed HIV infection
  3. Stable antiviral regimen for at least 12 weeks prior to enrollment
  4. WC>95 cm and WHR>0.94 for male, WC>94 cm and WHR>0.88 for female occurring in the context of treatment for HIV disease
  5. Subjective evidence of at least one of the following recent changes, occurring during the treatment of HIV disease: increased abdominal girth, relative loss of fat in the extremities, or relative loss of fat in the face
  6. For female subjects 40yo or older, negative mammogram within one year of baseline

Exclusion Criteria:

  1. Use of anti-diabetic agents, Megace, testosterone or any steroid use within 6 months of the study. Stable use of testosterone (> 6 mos) at dose equivalent to 200 mg IM q 2 weeks or < 10g/day to skin will be permitted.
  2. Use of GH or GHRH within the past 6 months
  3. Change in lipid lowering or antihypertensive regimen within 3 months of screening
  4. Fasting blood sugar > 126 mg/dL, SGOT > 2.5 times ULN, HgB < 12.0 g/dL, creatinine > 1.4 mg/dL, CD4 count < 200
  5. Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer
  6. For men, history of prostate cancer or evidence of prostate malignancy by PSA > 5 ng/mL
  7. Prior history of hypopituitarism, head irradiation or any other condition known to affect the GH axis
  8. For women, positive urine hCG
  9. Oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study.
  10. Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01263717

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Investigators
Principal Investigator: Steven Grinspoon, MD Massachusetts General Hospital
  More Information

Publications:
Responsible Party: Steven K. Grinspoon, MD, Professor of Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01263717     History of Changes
Other Study ID Numbers: 2007p-000638
Study First Received: December 16, 2010
Results First Received: September 8, 2014
Last Updated: October 10, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
HIV
lipodystrophy
tesamorelin
Egrifta
growth hormone releasing hormone

Additional relevant MeSH terms:
Lipodystrophy
Skin Diseases, Metabolic
Skin Diseases
Lipid Metabolism Disorders
Metabolic Diseases
Hormones
Growth Hormone-Releasing Hormone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 19, 2014