Effects of Growth Hormone Releasing Hormone in HIV

• ClinicalTrials.gov Identifier: NCT01263717
• Recruitment Status: Completed
• First Posted: December 21, 2010
• Results First Posted: October 13, 2014
• Last Update Posted: October 30, 2017
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Steven K. Grinspoon, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: December 16, 2010
• First Posted Date: December 21, 2010
• Results First Submitted Date: September 8, 2014
• Results First Posted Date: October 13, 2014
• Last Update Posted Date: October 30, 2017
• Study Start Date: December 2010
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2014)

• Liver Fat [ Time Frame: 6 months ]
  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 ]
  Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra.

Original Primary Outcome Measures (submitted: December 20, 2010)

• Liver fat [ Time Frame: 6 months ]
  Hepatic fat as measured by magnetic resonance (MR) spectroscopy.
• Visceral Adipose Tissue [ Time Frame: 6 months ]
  Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra.

Current Secondary Outcome Measures (submitted: October 10, 2014)

• Intramyocellular Lipid [ Time Frame: 6 months ]
  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 ]
  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 ]
  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 ]
  Hemoglobin A1c.
• Insulin Like Growth Factor 1 (IGF-I) [ Time Frame: 6 months ]
  Insulin Like Growth Factor 1 (IGF-I).
• Lipid Panel [ Time Frame: 6 months ]
  Fasting lipids. Triglyceride value is given.
• Carotid Intimal Medial Thickness (cIMT) [ Time Frame: 6 months ]
  Carotid Intimal Medial Thickness (cIMT).
• Glucose Tolerance [ Time Frame: 6 months ]
  Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.
• Adiponectin [ Time Frame: 6 months ]
  adiponectin.
• Hemostatic Markers [ Time Frame: 6 months ]
  Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.

Original Secondary Outcome Measures (submitted: December 20, 2010)

• Intramyocellular Lipid [ Time Frame: 6 months ]
  Intramyocellular lipid as measured by magnetic resonance (MR) spectroscopy of the calf.
• Endogenous growth hormone secretion [ Time Frame: 6 months ]
  Endogenous growth hormone concentrations will be measured by overnight freqent blood sampling, and a deconvolution algorithm will be used to characterize the pulsatility of secretion.
• Insulin sensitivity [ Time Frame: 6 months ]
  In a subgroup of 1/2 of the subjects, euglycemic hyperinsulinemic clamp will be performed to assess insulin-stimulated glucose uptake.
• HbA1c [ Time Frame: 6 months ]
  Hemoglobin A1c.
• Insulin Like Growth Factor 1 (IGF-I) [ Time Frame: 6 months ]
  Insulin Like Growth Factor 1 (IGF-I).
• Lipid panel [ Time Frame: 6 months ]
  Fasting lipids as well as lipoprotein (a), Apoprotein B, Apoprotein A1, low density lipid (LDL) particle size, lipoprotein-associated phospholipase A2 (Lp-PLA2).
• Carotid Intimal Medial Thickness (cIMT) [ Time Frame: 6 months ]
  Carotid Intimal Medial Thickness (cIMT).
• Glucose tolerance [ Time Frame: 6 months ]
  Glucose tolerance as measured by standard oral glucose tolerance test.
• adiponectin [ Time Frame: 6 months ]
  adiponectin.
• hemostatic markers [ Time Frame: 6 months ]
  Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effects of Growth Hormone Releasing Hormone in HIV
• Official Title: Effects of Growth Hormone Releasing Hormone on Fat Redistribution, Cardiovascular Indices, and Growth Hormone Secretion in HIV Lipodystrophy
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• HIV
• HIV Lipodystrophy

Intervention

• 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
• 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

Study Arms

• 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
  Intervention: Drug: tesamorelin
• 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
  Intervention: Drug: placebo

Publications *

• Stanley TL, Feldpausch MN, Oh J, Branch KL, Lee H, Torriani M, Grinspoon SK. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation: a randomized clinical trial. JAMA. 2014 Jul 23-30;312(4):380-9. doi: 10.1001/jama.2014.8334.
• Braun LR, Feldpausch MN, Czerwonka N, Torriani M, Grinspoon SK, Stanley TL. Fibroblast growth factor 21 decreases after liver fat reduction via growth hormone augmentation. Growth Horm IGF Res. 2017 Dec;37:1-6. doi: 10.1016/j.ghir.2017.10.002. Epub 2017 Oct 7.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 10, 2014): 54
• Original Estimated Enrollment (submitted: December 20, 2010): 60
• Actual Study Completion Date: February 2014
• Actual Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older 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: NCT01263717
• Other Study ID Numbers: 2007p-000638
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Steven K. Grinspoon, MD, Massachusetts General Hospital
• Original Responsible Party: Steven K. Grinspoon, M.D., Massachusetts General Hospital
• Current Study Sponsor: Massachusetts General Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Steven Grinspoon, MD; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: September 2017