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Effects of Growth Hormone Releasing Hormone in HIV

Primary Purpose

HIV, HIV Lipodystrophy

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

tesamorelin

placebo

About this trial

This is an interventional treatment trial for HIV focused on measuring HIV, lipodystrophy, tesamorelin, Egrifta, growth hormone releasing hormone

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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.
Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.

Sites / Locations

Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Tesamorelin

Placebo (inactive injection)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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).

Visceral Adipose Tissue

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

Secondary Outcome Measures

Intramyocellular Lipid

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

Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given.

Insulin Sensitivity

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

Hemoglobin A1c.

Insulin Like Growth Factor 1 (IGF-I)

Insulin Like Growth Factor 1 (IGF-I).

Lipid Panel

Fasting lipids. Triglyceride value is given.

Carotid Intimal Medial Thickness (cIMT)

Carotid Intimal Medial Thickness (cIMT).

Glucose Tolerance

Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.

Adiponectin

adiponectin.

Hemostatic Markers

Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.

Full Information

NCT ID

NCT01263717

First Posted

December 16, 2010

Last Updated

September 28, 2017

Sponsor

Massachusetts General Hospital

1. Study Identification

Unique Protocol Identification Number

NCT01263717

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

Study Type

Interventional

2. Study Status

Record Verification Date

September 2017

Overall Recruitment Status

Completed

Study Start Date

December 2010 (undefined)

Primary Completion Date

February 2014 (Actual)

Study Completion Date

February 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

HIV, HIV Lipodystrophy

Keywords

HIV, lipodystrophy, tesamorelin, Egrifta, growth hormone releasing hormone

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

54 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Tesamorelin

Arm Type

Experimental

Arm Description

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

Arm Title

Placebo (inactive injection)

Arm Type

Placebo Comparator

Arm Description

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 Type

Drug

Intervention Name(s)

tesamorelin

Other Intervention Name(s)

Egrifta, growth hormone releasing hormone, TH9507

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

placebo

Intervention Description

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

Primary Outcome Measure Information:

Title

Liver Fat

Description

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).

Time Frame

6 months

Title

Visceral Adipose Tissue

Description

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

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Intramyocellular Lipid

Description

Time Frame

6 months

Title

Endogenous Growth Hormone Secretion

Description

Endogenous growth hormone (GH) concentrations measured by overnight frequent blood sampling every 20 minutes. Mean overnight GH concentration is given.

Time Frame

6 months

Title

Insulin Sensitivity

Description

Time Frame

6 months

Title

HbA1c

Description

Hemoglobin A1c.

Time Frame

6 months

Title

Insulin Like Growth Factor 1 (IGF-I)

Description

Insulin Like Growth Factor 1 (IGF-I).

Time Frame

6 months

Title

Lipid Panel

Description

Fasting lipids. Triglyceride value is given.

Time Frame

6 months

Title

Carotid Intimal Medial Thickness (cIMT)

Description

Carotid Intimal Medial Thickness (cIMT).

Time Frame

6 months

Title

Glucose Tolerance

Description

Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.

Time Frame

6 months

Title

Adiponectin

Description

adiponectin.

Time Frame

6 months

Title

Hemostatic Markers

Description

Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 Exclusion Criteria: 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. Routine MRI exclusion criteria such as the presence of a pacemaker or cerebral aneurysm clip.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven Grinspoon, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

25038357

Citation

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.

Results Reference

result

PubMed Identifier

29031905

Citation

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.

Results Reference

derived

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Effects of Growth Hormone Releasing Hormone in HIV

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