Effects of Short-term Growth Hormone in HIV-infected Patients

• ClinicalTrials.gov Identifier: NCT00795210
• Recruitment Status: Completed
• First Posted: November 21, 2008
• Results First Posted: January 8, 2014
• Last Update Posted: January 8, 2014
• Sponsor: Massachusetts General Hospital
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Steven K. Grinspoon, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: November 20, 2008
• First Posted Date: November 21, 2008
• Results First Submitted Date: October 9, 2013
• Results First Posted Date: January 8, 2014
• Last Update Posted Date: January 8, 2014
• Study Start Date: February 2009
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 6, 2013)

Overnight Mean Growth Hormone Secretion After 2 Weeks of Study Drug [ Time Frame: after 2 weeks treatment ]

Serum was sampled for growth hormone concentrations every 20 minutes between 20:00 (8pm) and 07:40 (7:40am). Subjects in GH 6mcg/kg/day and GH 2mg daily groups received their final dose of study drug approximately 36 hours prior to start of sampling. Subjects in Growth Hormone Releasing Hormone group received their final dose of study drug approximately 8 hours prior to start of sampling.

• Original Primary Outcome Measures (submitted: November 20, 2008): Overnight mean growth hormone secretion [ Time Frame: after 2 weeks treatment and 2 weeks withdrawal ]

Current Secondary Outcome Measures (submitted: December 6, 2013)

Insulin Sensitivity [ Time Frame: after two weeks treatment ]

insulin-stimulated glucose uptake as measured by euglycemic hyperinsulinemic clamp; "M" value (infusion rate with space correction, using method of DeFronzo) for the steady state between 100-120 minutes of clamp is given

• Original Secondary Outcome Measures (submitted: November 20, 2008): Insulin Sensitivity [ Time Frame: after two weeks treatment and two weeks withdrawal ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Short-term Growth Hormone in HIV-infected Patients
• Official Title: Effects of Short-term Growth Hormone in HIV-infected Patients
• Brief Summary: The purpose of this study is to examine the short-term effects of two different doses of growth hormone, compared to treatment with growth hormone releasing hormone, on the brain's secretion of growth hormone and the body's glucose metabolism. We hypothesize that growth hormone administration will alter the body's endogenous pulsatile growth hormone secretion and that higher dose growth hormone may decrease insulin sensitivity. We hypothesize that growth hormone releasing hormone will augment endogenous GH pulsatility and be neutral to insulin sensitivity.
• Detailed Description: The primary objective of this study is to determine the differential effects of growth hormone releasing hormone (GHRH) vs. low dose physiologic growth hormone (GH) vs. higher dose GH treatment and withdrawal on endogenous overnight growth hormone secretion and pulsatility, as well as insulin-stimulated glucose uptake. Subjects with HIV-infection will be randomized to receive one of three treatments: GHRH 2mg/day, or growth hormone 6mcg/kg/day (physiologic "low" dose), or growth hormone 2mg/day ("higher" dose) for 2 weeks. At baseline and after two weeks of treatment, we will assess overnight growth hormone by frequent sampling as well as insulin stimulated glucose uptake by clamp. Subjects will then stop the treatment and will return for an identical assessment after a 2 week withdrawal period.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV Lipodystrophy

Intervention

• Drug: Growth hormone
  Recombinant Human Growth Hormone (Teva pharmaceuticals), with one arm receiving 6mcg/kg SC once daily for two weeks and the other arm receiving 2mg SC once daily for two weeks
  Other Name: rhGH from Teva Pharmaceuticals
• Drug: Growth Hormone Releasing Hormone
  Tesamorelin (GHRH) 2mg SC QD x 2 weeks

Study Arms

• Experimental: GH 6mcg/kg/d
  Recombinant human growth hormone 6mcg/kg SC once daily
  Intervention: Drug: Growth hormone
• Experimental: GH 2mg daily
  Recombinant human growth hormone 2mg SC once daily
  Intervention: Drug: Growth hormone
• Experimental: Growth Hormone Releasing Hormone
  Growth Hormone Releasing Hormone (Tesamorelin) 2mg daily, injected subcutaneously, x 2 weeks
  Intervention: Drug: Growth Hormone Releasing Hormone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 9, 2012): 25
• Original Estimated Enrollment (submitted: November 20, 2008): 51
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• previously diagnosed HIV infection
• Stable antiretroviral regimen for at least 12 weeks prior to enrollment
• Waist circumference >/= 95cm and waist-to-hip ratio >/= 0.94 for males or waist circumference >/=94cm and WHR >/= 0.88 for females, occurring in the context of treatment for HIV disease
• Subjective evidence of at least one of the following 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

Exclusion Criteria:

• Use of anti-diabetic agents, Megace, testosterone, or any steroid use within 6 months of the study
• Use of GH or Growth hormone releasing factor within six months of starting the study
• Change in lipid lowering or antihypertensive regimen within 3 months of screening
• Fasting blood sugar >126mg/dL, SGOT > 2.5 times ULN, Hgb < 12.0 g/dL, creatinine > 1.4 mg/dL, FSH > 20 IU/L in women, or CD4 count < 200
• Carpal tunnel syndrome
• Severe chronic illness or active malignancy or history of pituitary malignancy or history of colon cancer
• For men, history of prostate cancer or evidence of prostate malignancy by PSA > 5ng/mL
• Prior history of hypopituitarism, head irradiation, or any other condition known to affect the GH axis
• positive beta-HCG (women only)
• Oral contraceptives, depo provera, or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study
• weight < 110 pounds

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00795210
• Other Study ID Numbers: DK63639A; R01DK063639 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Steven K. Grinspoon, MD, Massachusetts General Hospital
• Study Sponsor: Massachusetts General Hospital
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Steven K Grinspoon, M.D.; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: October 2013