Physiologic Growth Hormone Effects in HIV Lipodystrophy

This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat. Secondary endpoints will include measures of insulin-like growth factor-1 (IGF-1), glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters.

Study Overview

• Status: Completed
• Conditions: HIV Infections; AIDS
• Intervention / Treatment: Drug: recombinant human growth hormone; Drug: placebo

Detailed Description

This study will investigate long-term, low-dose growth hormone administration in HIV-infected patients with reduced growth hormone (GH) secretion and increased visceral adiposity. We hypothesize that low-dose growth hormone will reduce visceral fat preferentially over subcutaneous fat, and increase lean body mass. Secondary endpoints will include measures of IGF-1, glucose homeostasis, lipids, blood pressure,bone density, cardiovascular risk and safety parameters. Dosing of growth hormone will be based on patients' IGF-1 levels and will not exceed 6mcg/kg/day.

• Study Type: Interventional
• Enrollment (Actual): 56
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • MGH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women age 18-60
• Previously diagnosed HIV infection
• Stable antiviral regimen for at least 12 weeks prior to enrollment
• Waist-to-hip ratio >0.90 for men and >0.85 for women

• Evidence of at least one of the following recent changes: *increased abdominal girth,

  *relative loss of fat in the extremities, *relative loss of fat in the face

• Simulated peak GH response to arginine/GHRH of less than 7.5 mcg/dL

Exclusion Criteria:

• Use of Megace, anti-diabetic agents, GH, or other anabolic agents, pharmacologic glucocorticoid (prednisone >5 mg/day or its equivalent) for 3 months prior to enrollment. Patients on a standard dose of testosterone for documented hypogonadism will be allowed to enter the protocol. Women taking standard estrogen replacement therapy for >3 months will be allowed in the study.
• Diabetes mellitus
• Other severe chronic illness
• HgB <9.0 g/dL, creatinine >1.4 mg/dL, or PSA >4 ng/mL
• Positive BHCG or failure to use appropriate birth control during study. Acceptable methods include oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, IUD's, barrier devices (condoms, diaphragms), and abstinence.
• Carpal tunnel syndrome
• Active malignancy or history of pituitary malignancy, history of colon cancer or prostate malignancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; recombinant human growth hormone subcutaneously once a day	Drug: recombinant human growth hormone; growth hormone dosed by weight and IGF-1 level,subcutaneously once a day, 18 months; Other Names: Serostim
Placebo Comparator: 2; placebo subcutaneously once a day	Drug: placebo; placebo subcutaneously once a day, 18 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Visceral Adipose Tissue Area From Baseline to 18 Months	change in visceral adipose tissue area as measured by single-slice abdominal computed tomographic scan	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Insulin-like Growth Factor-I From Baseline to 18 Months	Change in insulin-like growth factor-1	18 months
Change in Trunk Fat		18 months
Change in Fasting Glucose	change in fasting glucose	18 months
Change in Trunk to Extremity Ratio	change in trunk to extremity ratio	18 months
Change in Triglycerides	Change in triglycerides	18 months
Change in Subcutaneous Adipose Tissue	Change in subcutaneous adipose tissue	18 months
Change in CD4 Cells	Change in CD4 cells	18 months
Change in Logarithm HIV Viral Load	Change in logarithm base 10 HIV viral load	18 months
Change in Lean Body Mass	change in lean body mass	18 months
Change in Quality of Life Score From the Medical Outcomes Study-HIV Survey From Baseline to 18 Months	Change in quality of life score was measured by the Medical Outcomes Study-HIV (MOS-HIV)survey. The MOS-HIV asks patients to report on health-related quality of life and physical function from the past 4 days. The scoring range is 0-100, and a higher score indicates better quality of life.	18 months
Change in Diastolic Blood Pressure	Change in diastolic blood pressure	18 months
Change in Adiponectin	Change in adiponectin	18 months
Change in Carotid Intima Media Thickness (IMT)	change in carotid intima media thickness (IMT)	18 months
Change in Body Mass Index	Change in body mass index	18 months
Change in Extremity Fat	Change in extremity fat	18 months
Change in 2-hour Glucose	Change in 2-hour glucose	18 months
Change in Systolic Blood Pressure	Change in systolic blood pressure	18 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Publications and helpful links

General Publications

• Lo J, You SM, Canavan B, Liebau J, Beltrani G, Koutkia P, Hemphill L, Lee H, Grinspoon S. Low-dose physiological growth hormone in patients with HIV and abdominal fat accumulation: a randomized controlled trial. JAMA. 2008 Aug 6;300(5):509-19. doi: 10.1001/jama.300.5.509.

Study record dates

Study Major Dates

• Study Start: January 1, 2004
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: January 4, 2005
• First Submitted That Met QC Criteria: January 4, 2005
• First Posted (Estimate): January 5, 2005

Study Record Updates

• Last Update Posted (Estimate): July 27, 2010
• Last Update Submitted That Met QC Criteria: July 22, 2010
• Last Verified: July 1, 2010

More Information

Terms related to this study

• Keywords: HIV; Treatment Experienced; growth hormone; visceral fat; lipodystrophy; IGF-I
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Lipid Metabolism Disorders; Skin Diseases, Metabolic; Lipodystrophy; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormones
• Other Study ID Numbers: DK63639; R01DK063639 (U.S. NIH Grant/Contract)