Effects of Growth Hormone Releasing Hormone in HIV

Sponsor
Massachusetts General Hospital (Other)
Overall Status
Completed
CT.gov ID
NCT01263717
Collaborator
(none)
54
1
2
38
1.4

Study Details

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.

Condition or Disease Intervention/Treatment Phase
N/A

Study Design

Study Type:
Interventional
Actual Enrollment :
54 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Effects of Growth Hormone Releasing Hormone on Fat Redistribution, Cardiovascular Indices, and Growth Hormone Secretion in HIV Lipodystrophy
Study Start Date :
Dec 1, 2010
Actual Primary Completion Date :
Feb 1, 2014
Actual Study Completion Date :
Feb 1, 2014

Arms and Interventions

Arm Intervention/Treatment
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

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 Names:
  • Egrifta, growth hormone releasing hormone, TH9507
  • 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

    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

    Outcome Measures

    Primary Outcome Measures

    1. Liver Fat [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).

    2. Visceral Adipose Tissue [6 months]

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

    Secondary Outcome Measures

    1. Intramyocellular Lipid [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.

    2. Endogenous Growth Hormone Secretion [6 months]

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

    3. Insulin Sensitivity [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.

    4. HbA1c [6 months]

      Hemoglobin A1c.

    5. Insulin Like Growth Factor 1 (IGF-I) [6 months]

      Insulin Like Growth Factor 1 (IGF-I).

    6. Lipid Panel [6 months]

      Fasting lipids. Triglyceride value is given.

    7. Carotid Intimal Medial Thickness (cIMT) [6 months]

      Carotid Intimal Medial Thickness (cIMT).

    8. Glucose Tolerance [6 months]

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

    9. Adiponectin [6 months]

      adiponectin.

    10. Hemostatic Markers [6 months]

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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Massachusetts General Hospital Boston Massachusetts United States 02114

    Sponsors and Collaborators

    • Massachusetts General Hospital

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Steven K. Grinspoon, MD, Professor of Medicine, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT01263717
    Other Study ID Numbers:
    • 2007p-000638
    First Posted:
    Dec 21, 2010
    Last Update Posted:
    Oct 30, 2017
    Last Verified:
    Sep 1, 2017
    Keywords provided by Steven K. Grinspoon, MD, Professor of Medicine, Massachusetts General Hospital
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Period Title: Overall Study
    STARTED 28 26
    Baseline Visit 28 22
    COMPLETED 23 20
    NOT COMPLETED 5 6

    Baseline Characteristics

    Arm/Group Title Tesamorelin Placebo (Inactive Injection) Total
    Arm/Group 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 Total of all reporting groups
    Overall Participants 28 22 50
    Age (years) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [years]
    49
    53
    51.5
    Sex: Female, Male (Count of Participants)
    Female
    4
    14.3%
    4
    18.2%
    8
    16%
    Male
    24
    85.7%
    18
    81.8%
    42
    84%
    Race/Ethnicity, Customized (participants) [Number]
    White
    20
    71.4%
    14
    63.6%
    34
    68%
    Black
    6
    21.4%
    3
    13.6%
    9
    18%
    Hispanic
    1
    3.6%
    3
    13.6%
    4
    8%
    Other
    1
    3.6%
    2
    9.1%
    3
    6%
    Region of Enrollment (participants) [Number]
    United States
    28
    100%
    22
    100%
    50
    100%

    Outcome Measures

    1. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for some subjects. Data from 1 patient who was discontinued between the 3 and 6mo visits for adverse event are included. These data were obtained at a termination visit.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 22 19
    Median (Inter-Quartile Range) [Change in hepatic lipid-to-water %]
    -2.0
    0.9
    2. Primary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    Data from 1 patient who was discontinued between the 3 and 6mo visits for adverse event are included. These data were obtained at a termination visit.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 24 20
    Mean (95% Confidence Interval) [change in cm^2 after 6 months]
    -34
    8
    3. Secondary Outcome
    Title Intramyocellular Lipid
    Description 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.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for some subjects. Data from 1 patient who was discontinued between the 3 and 6mo visits for adverse event are included. These data were obtained at a termination visit.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 23 20
    Median (Inter-Quartile Range) [Change in ratio of IMCL/Cr]
    -1.7
    -0.2
    4. Secondary Outcome
    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

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for some subjects.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 21 15
    Median (Inter-Quartile Range) [Change in ng/mL]
    0.35
    -0.01
    5. Secondary Outcome
    Title Insulin Sensitivity
    Description 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.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for some subjects.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 10 9
    Mean (95% Confidence Interval) [Change in mg/kg/min]
    0.4
    0.7
    6. Secondary Outcome
    Title HbA1c
    Description Hemoglobin A1c.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for one subject.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 22 20
    Mean (95% Confidence Interval) [Change in %]
    0.20
    0.02
    7. Secondary Outcome
    Title Insulin Like Growth Factor 1 (IGF-I)
    Description Insulin Like Growth Factor 1 (IGF-I).
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for one subject.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 22 20
    Mean (Standard Deviation) [Change in ng/mL]
    79
    (92)
    7
    (62)
    8. Secondary Outcome
    Title Lipid Panel
    Description Fasting lipids. Triglyceride value is given.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for one subject.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 22 20
    Median (Inter-Quartile Range) [Change in triglyceride, mg/dL]
    -25
    -10
    9. Secondary Outcome
    Title Carotid Intimal Medial Thickness (cIMT)
    Description Carotid Intimal Medial Thickness (cIMT).
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 23 20
    Mean (95% Confidence Interval) [Change in mm]
    -0.03
    -0.00
    10. Secondary Outcome
    Title Glucose Tolerance
    Description Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used; data were not available for some subjects.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 22 18
    Mean (95% Confidence Interval) [Change in 2-hour glucose, mg/dL]
    -1
    -8
    11. Secondary Outcome
    Title Adiponectin
    Description adiponectin.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    All available data were used. Data were not available for 1 subject.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 22 20
    Median (Inter-Quartile Range) [Change in ng/mL]
    0
    0
    12. Secondary Outcome
    Title Hemostatic Markers
    Description Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.
    Time Frame 6 months

    Outcome Measure Data

    Analysis Population Description
    Please note that we do not have data for these markers (neither PAI1 or tPA) because we did not have adequate funds to assess these.
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    Measure Participants 0 0

    Adverse Events

    Time Frame 6 month randomized portion of study
    Adverse Event Reporting Description
    Arm/Group Title Tesamorelin Placebo (Inactive Injection)
    Arm/Group 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
    All Cause Mortality
    Tesamorelin Placebo (Inactive Injection)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Tesamorelin Placebo (Inactive Injection)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/28 (10.7%) 3/22 (13.6%)
    Cardiac disorders
    Congestive Heart Failure 1/28 (3.6%) 1 0/22 (0%) 0
    Gastrointestinal disorders
    esophageal myotomy 0/28 (0%) 0 1/22 (4.5%) 1
    Respiratory, thoracic and mediastinal disorders
    pneumonia 1/28 (3.6%) 1 0/22 (0%) 0
    Skin and subcutaneous tissue disorders
    basal cell carcinoma 1/28 (3.6%) 1 1/22 (4.5%) 1
    Vascular disorders
    cerebrovascular accident 0/28 (0%) 0 1/22 (4.5%) 1
    Other (Not Including Serious) Adverse Events
    Tesamorelin Placebo (Inactive Injection)
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 25/28 (89.3%) 21/22 (95.5%)
    Blood and lymphatic system disorders
    edema 2/28 (7.1%) 1/22 (4.5%)
    Endocrine disorders
    hyperglycemia 2/28 (7.1%) 2/22 (9.1%)
    Infections and infestations
    sinusitis 2/28 (7.1%) 1/22 (4.5%)
    Musculoskeletal and connective tissue disorders
    joint pain 4/28 (14.3%) 4/22 (18.2%)
    muscle pain 3/28 (10.7%) 0/22 (0%)
    Nervous system disorders
    paresthesia 6/28 (21.4%) 1/22 (4.5%)
    Skin and subcutaneous tissue disorders
    injection site bruising 10/28 (35.7%) 11/22 (50%)
    erythema at injection site 4/28 (14.3%) 2/22 (9.1%)
    stinging of skin 3/28 (10.7%) 0/22 (0%)

    Limitations/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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Steven K. Grinspoon, MD
    Organization Massachusetts General Hospital
    Phone 617-724-9109
    Email sgrinspoon@partners.org
    Responsible Party:
    Steven K. Grinspoon, MD, Professor of Medicine, Massachusetts General Hospital
    ClinicalTrials.gov Identifier:
    NCT01263717
    Other Study ID Numbers:
    • 2007p-000638
    First Posted:
    Dec 21, 2010
    Last Update Posted:
    Oct 30, 2017
    Last Verified:
    Sep 1, 2017