Trial Outcomes & Findings for Effects of Growth Hormone Releasing Hormone in HIV (NCT NCT01263717)

NCT ID: NCT01263717

Last Updated: 2017-10-30

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 54 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2017-10-30

Participant Flow

Participant milestones

Measure	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	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
Overall Study STARTED	28	26
Overall Study Baseline Visit	28	22
Overall Study COMPLETED	23	20
Overall Study NOT COMPLETED	5	6

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Effects of Growth Hormone Releasing Hormone in HIV

Baseline characteristics by cohort

Measure	Tesamorelin n=28 Participants 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 (Inactive Injection) n=22 Participants 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 n=50 Participants Total of all reporting groups
Age, Continuous	49 years n=5 Participants	53 years n=7 Participants	51.5 years n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	18 Participants n=7 Participants	42 Participants n=5 Participants
Race/Ethnicity, Customized White	20 participants n=5 Participants	14 participants n=7 Participants	34 participants n=5 Participants
Race/Ethnicity, Customized Black	6 participants n=5 Participants	3 participants n=7 Participants	9 participants n=5 Participants
Race/Ethnicity, Customized Hispanic	1 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants
Race/Ethnicity, Customized Other	1 participants n=5 Participants	2 participants n=7 Participants	3 participants n=5 Participants
Region of Enrollment United States	28 participants n=5 Participants	22 participants n=7 Participants	50 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 months

Population: 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.

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).

Outcome measures

Measure	Tesamorelin n=22 Participants 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 (Inactive Injection) n=19 Participants 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
Liver Fat	-2.0 Change in hepatic lipid-to-water % Interval -6.4 to 0.1	0.9 Change in hepatic lipid-to-water % Interval -0.6 to 3.7

PRIMARY outcome

Timeframe: 6 months

Population: 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.

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

Outcome measures

Measure	Tesamorelin n=24 Participants 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 (Inactive Injection) n=20 Participants 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
Visceral Adipose Tissue	-34 change in cm^2 after 6 months Interval -53.0 to -15.0	8 change in cm^2 after 6 months Interval -14.0 to 30.0

SECONDARY outcome

Timeframe: 6 months

Population: 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.

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.

Outcome measures

Measure	Tesamorelin n=23 Participants 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 (Inactive Injection) n=20 Participants 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
Intramyocellular Lipid	-1.7 Change in ratio of IMCL/Cr Interval -3.9 to 0.7	-0.2 Change in ratio of IMCL/Cr Interval -5.2 to 5.5

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used; data were not available for some subjects.

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

Outcome measures

Measure	Tesamorelin n=21 Participants 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 (Inactive Injection) n=15 Participants 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
Endogenous Growth Hormone Secretion	0.35 Change in ng/mL Interval 0.15 to 0.57	-0.01 Change in ng/mL Interval -0.07 to 0.06

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used; data were not available for some subjects.

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.

Outcome measures

Measure	Tesamorelin n=10 Participants 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 (Inactive Injection) n=9 Participants 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
Insulin Sensitivity	0.4 Change in mg/kg/min Interval -1.2 to 1.9	0.7 Change in mg/kg/min Interval -0.6 to 2.1

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used; data were not available for one subject.

Hemoglobin A1c.

Outcome measures

Measure	Tesamorelin n=22 Participants 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 (Inactive Injection) n=20 Participants 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
HbA1c	0.20 Change in % Interval 0.04 to 0.36	0.02 Change in % Interval -0.07 to 0.1

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used; data were not available for one subject.

Insulin Like Growth Factor 1 (IGF-I).

Outcome measures

Measure	Tesamorelin n=22 Participants 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 (Inactive Injection) n=20 Participants 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
Insulin Like Growth Factor 1 (IGF-I)	79 Change in ng/mL Standard Deviation 92	7 Change in ng/mL Standard Deviation 62

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used; data were not available for one subject.

Fasting lipids. Triglyceride value is given.

Outcome measures

Measure	Tesamorelin n=22 Participants 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 (Inactive Injection) n=20 Participants 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
Lipid Panel	-25 Change in triglyceride, mg/dL Interval -68.0 to 8.0	-10 Change in triglyceride, mg/dL Interval -33.0 to 8.0

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used.

Carotid Intimal Medial Thickness (cIMT).

Outcome measures

Measure	Tesamorelin n=23 Participants 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 (Inactive Injection) n=20 Participants 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
Carotid Intimal Medial Thickness (cIMT)	-0.03 Change in mm Interval -0.07 to 0.0	-0.00 Change in mm Interval -0.03 to 0.03

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used; data were not available for some subjects.

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

Outcome measures

Measure	Tesamorelin n=22 Participants 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 (Inactive Injection) n=18 Participants 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
Glucose Tolerance	-1 Change in 2-hour glucose, mg/dL Interval -18.0 to 15.0	-8 Change in 2-hour glucose, mg/dL Interval -24.0 to 8.0

SECONDARY outcome

Timeframe: 6 months

Population: All available data were used. Data were not available for 1 subject.

adiponectin.

Outcome measures

Measure	Tesamorelin n=22 Participants 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 (Inactive Injection) n=20 Participants 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
Adiponectin	0 Change in ng/mL Interval -515.0 to 1159.0	0 Change in ng/mL Interval -1030.0 to 515.0

SECONDARY outcome

Timeframe: 6 months

Population: 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.

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

Outcome measures

Outcome data not reported

Adverse Events

Tesamorelin

Serious events: 3 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo (Inactive Injection)

Serious events: 3 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Measure	Tesamorelin n=28 participants at risk 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 (Inactive Injection) n=22 participants at risk 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
Cardiac disorders Congestive Heart Failure	3.6% 1/28 • Number of events 1 • 6 month randomized portion of study	0.00% 0/22 • 6 month randomized portion of study
Respiratory, thoracic and mediastinal disorders pneumonia	3.6% 1/28 • Number of events 1 • 6 month randomized portion of study	0.00% 0/22 • 6 month randomized portion of study
Skin and subcutaneous tissue disorders basal cell carcinoma	3.6% 1/28 • Number of events 1 • 6 month randomized portion of study	4.5% 1/22 • Number of events 1 • 6 month randomized portion of study
Gastrointestinal disorders esophageal myotomy	0.00% 0/28 • 6 month randomized portion of study	4.5% 1/22 • Number of events 1 • 6 month randomized portion of study
Vascular disorders cerebrovascular accident	0.00% 0/28 • 6 month randomized portion of study	4.5% 1/22 • Number of events 1 • 6 month randomized portion of study

Other adverse events

Measure	Tesamorelin n=28 participants at risk 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 (Inactive Injection) n=22 participants at risk 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
Skin and subcutaneous tissue disorders injection site bruising	35.7% 10/28 • 6 month randomized portion of study	50.0% 11/22 • 6 month randomized portion of study
Nervous system disorders paresthesia	21.4% 6/28 • 6 month randomized portion of study	4.5% 1/22 • 6 month randomized portion of study
Skin and subcutaneous tissue disorders erythema at injection site	14.3% 4/28 • 6 month randomized portion of study	9.1% 2/22 • 6 month randomized portion of study
Musculoskeletal and connective tissue disorders joint pain	14.3% 4/28 • 6 month randomized portion of study	18.2% 4/22 • 6 month randomized portion of study
Skin and subcutaneous tissue disorders stinging of skin	10.7% 3/28 • 6 month randomized portion of study	0.00% 0/22 • 6 month randomized portion of study
Musculoskeletal and connective tissue disorders muscle pain	10.7% 3/28 • 6 month randomized portion of study	0.00% 0/22 • 6 month randomized portion of study
Endocrine disorders hyperglycemia	7.1% 2/28 • 6 month randomized portion of study	9.1% 2/22 • 6 month randomized portion of study
Blood and lymphatic system disorders edema	7.1% 2/28 • 6 month randomized portion of study	4.5% 1/22 • 6 month randomized portion of study
Infections and infestations sinusitis	7.1% 2/28 • 6 month randomized portion of study	4.5% 1/22 • 6 month randomized portion of study

Additional Information

Steven K. Grinspoon, MD

Massachusetts General Hospital

Phone: 617-724-9109

Email: sgrinspoon@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place