Effects of Growth Hormone Releasing Hormone in HIV

NCT01263717 | Completed Results DMC

• 1 other identifier: 2007p-000638
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV; HIV Lipodystrophy

Keywords

HIV; lipodystrophy; tesamorelin; Egrifta; growth hormone releasing hormone

Outcome Measures

Primary Outcomes (2)

• Liver Fat

  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).

  6 months

• Visceral Adipose Tissue

  Change in visceral adipose tissue area as measured by single-slice computed tomography (CT) scan at the L4 vertebra.

  6 months

Secondary Outcomes (10)

• Intramyocellular Lipid

  6 months

• Endogenous Growth Hormone Secretion

  6 months

• Insulin Sensitivity

  6 months

• HbA1c

  6 months

• Insulin Like Growth Factor 1 (IGF-I)

  6 months

Study Arms (2)

Tesamorelin

EXPERIMENTAL

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

Placebo (inactive injection)

PLACEBO COMPARATOR

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

Interventions

tesamorelin DRUG

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

Also known as: Egrifta, growth hormone releasing hormone, TH9507

Tesamorelin

placebo DRUG

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

Placebo (inactive injection)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women age 18-65
• Previously diagnosed HIV infection
• Stable antiviral regimen for at least 12 weeks prior to enrollment
• 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
• 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
• For female subjects 40yo or older, negative mammogram within one year of baseline

You may not qualify if:

• 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.
• Use of GH or GHRH within the past 6 months
• Change in lipid lowering or antihypertensive regimen within 3 months of screening
• Fasting blood sugar \> 126 mg/dL, SGOT \> 2.5 times ULN, HgB \< 12.0 g/dL, creatinine \> 1.4 mg/dL, CD4 count \< 200
• 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 \> 5 ng/mL
• Prior history of hypopituitarism, head irradiation or any other condition known to affect the GH axis
• For women, positive urine hCG
• Oral contraceptives, depo provera or combined progesterone-estrogen injections, transdermal contraceptive patches, estrogen or progestin coated IUD's within 6 months of the study.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (2)

• 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.

  PMID: 25038357 RESULT

• 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.

  PMID: 29031905 DERIVED

MeSH Terms

Conditions

Lipodystrophy

Interventions

tesamorelin; Growth Hormone-Releasing Hormone

Condition Hierarchy (Ancestors)

Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Limitations and Caveats

Please note that we intended to collect and analyze data on PAI1 and tPA but we did not have sufficient funds to do this.

Results Point of Contact

• Title: Steven K. Grinspoon, MD
• Organization: Massachusetts General Hospital

sgrinspoon@partners.org

617-724-9109

Study Officials

• Steven Grinspoon, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: December 16, 2010
• First Posted: December 21, 2010
• Study Start: December 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: October 30, 2017
• Results First Posted: October 13, 2014

Record last verified: 2017-09

Locations

US (1)