Effects of Growth Hormone Releasing Hormone in HIV
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
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:
|
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
- 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).
- 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
- 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.
- 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.
- 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.
- HbA1c [6 months]
Hemoglobin A1c.
- Insulin Like Growth Factor 1 (IGF-I) [6 months]
Insulin Like Growth Factor 1 (IGF-I).
- Lipid Panel [6 months]
Fasting lipids. Triglyceride value is given.
- Carotid Intimal Medial Thickness (cIMT) [6 months]
Carotid Intimal Medial Thickness (cIMT).
- Glucose Tolerance [6 months]
Glucose tolerance as measured by standard oral glucose tolerance test. 2-hour glucose is given.
- Adiponectin [6 months]
adiponectin.
- Hemostatic Markers [6 months]
Tissue plasminogen activator (tPA) and plasminogen activator inhibitor-1 (PAI-1) measured in serum.
Eligibility Criteria
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.
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.- 2007p-000638
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
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
|
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
|
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
|
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
|
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
|
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
|
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)
|
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
|
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
|
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
|
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
|
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
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 |
sgrinspoon@partners.org |
- 2007p-000638