Trial Outcomes & Findings for Effectiveness of Growth Hormone Releasing Hormone in Reducing Abdominal Fat in People Who Are Obese (NCT NCT00675506)

Last Updated: 2017-12-13

Results Overview

Abdominal visceral adipose tissue and subcutaneous adipose tissue were assessed using a single crosssectional slice from noncontrast computed tomography at the L4 level. The change in abdominal visceral adiposity between baseline and twelve months is reported.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

60 participants

Primary outcome timeframe

Measured at baseline and Months 6 and 12

Results posted on

2017-12-13

Participant Flow

Participant milestones

Participant milestones
Measure	TH9507 Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months	Placebo Participants received treatment with placebo medication. Placebo : 2-mg sub-cutaneous abdominal injections once daily for 12 months
Overall Study STARTED	31	29
Overall Study Received Intervention	29	29
Overall Study COMPLETED	19	17
Overall Study NOT COMPLETED	12	12

Reasons for withdrawal

Reasons for withdrawal
Measure	TH9507 Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months	Placebo Participants received treatment with placebo medication. Placebo : 2-mg sub-cutaneous abdominal injections once daily for 12 months
Overall Study Lost to Follow-up	1	5
Overall Study Lost interest	3	5
Overall Study Elevated fasting glucose	2	1
Overall Study Elevated IGF-1 prior to treatment	1	0
Overall Study Elevated IGF-1	2	0
Overall Study Hypersensitivity Reaction	1	0
Overall Study Disclosed history of cancer	1	0
Overall Study Declined participation	1	0
Overall Study Schedule conflict	0	1

Baseline Characteristics

Effectiveness of Growth Hormone Releasing Hormone in Reducing Abdominal Fat in People Who Are Obese

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	TH9507 n=31 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months	Placebo n=29 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	31 Participants n=5 Participants	29 Participants n=7 Participants	60 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	42.5 years STANDARD_DEVIATION 7.1 • n=5 Participants	39.9 years STANDARD_DEVIATION 9.5 • n=7 Participants	41.2 years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	20 Participants n=5 Participants	19 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment United States	31 participants n=5 Participants	29 participants n=7 Participants	60 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured at baseline and Months 6 and 12

Population: All data were included in the analysis by intention to treat principle. For participants who did not complete a 12-month visit, last observation carried forward was performed for those participants for whom interim data post the baseline visit was available. Data from 6 month is utilized in the linear mixed effects modeling.

Outcome measures

Outcome measures
Measure	TH9507 n=29 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). TH9507: Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months.	Placebo n=29 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Change in Visceral Adipose Tissue Volume	-16 cm2 Standard Error 9	19 cm2 Standard Error 9

SECONDARY outcome

Timeframe: Measured at baseline and Months 6 and 12

Carotid intima media thickness imaging of the common carotid artery was conducted using a high-resolution 7.5-MHz phased-array transducer (SONOS 2000/2500. The change of the carotid intima media thickness measurement between baseline and 12 months is reported.

Outcome measures

Outcome measures
Measure	TH9507 n=29 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). TH9507: Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months.	Placebo n=29 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Change in Carotid Intima-media Thickness	-0.03 mm Standard Error 0.01	0.01 mm Standard Error 0.01

SECONDARY outcome

Timeframe: Measured at baseline and Months 6 and 12

Lipid Profile (total cholesterol, high-density lipoproteins \[HDL\] cholesterol, low-density lipoproteins \[LDL\] cholesterol, triglycerides)was determined after an overnight fast. The change in lipid profile between baseline and 12 months is reported.

Outcome measures

Outcome measures
Measure	TH9507 n=29 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). TH9507: Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months.	Placebo n=29 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Change in Lipid Profile (Total Cholesterol, High-density Lipoproteins [HDL] Cholesterol, Low-density Lipoproteins [LDL] Cholesterol, Triglycerides) Total Cholesterol	4 mg/dL Standard Error 4	7 mg/dL Standard Error 5
Change in Lipid Profile (Total Cholesterol, High-density Lipoproteins [HDL] Cholesterol, Low-density Lipoproteins [LDL] Cholesterol, Triglycerides) High-density lipoproteins [HDL] cholesterol	4 mg/dL Standard Error 1	3 mg/dL Standard Error 1
Change in Lipid Profile (Total Cholesterol, High-density Lipoproteins [HDL] Cholesterol, Low-density Lipoproteins [LDL] Cholesterol, Triglycerides) Low-density lipoproteins [LDL] cholesterol	4 mg/dL Standard Error 4	1 mg/dL Standard Error 4
Change in Lipid Profile (Total Cholesterol, High-density Lipoproteins [HDL] Cholesterol, Low-density Lipoproteins [LDL] Cholesterol, Triglycerides) Triglycerides	-26 mg/dL Standard Error 16	12 mg/dL Standard Error 8

SECONDARY outcome

Timeframe: Measured at baseline and Months 6 and 12

Glucose tolerance was determined after an overnight fast using standard 75 gram oral glucose tolerance test (OGTT) with glucose measured at timepoints 0, 30, 60, 90 and 120. Change in glucose tolerance (fasting and 2 hour OGTT) between baseline and twelve months is reported.

Outcome measures

Outcome measures
Measure	TH9507 n=29 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). TH9507: Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months.	Placebo n=29 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Change in Glucose Tolerance as Measured by Oral Glucose Tolerance Test Fasting Glucose	2 mg/dL Standard Error 3	1 mg/dL Standard Error 2
Change in Glucose Tolerance as Measured by Oral Glucose Tolerance Test 2 Hour OGTT Glucose	-11 mg/dL Standard Error 7	-3 mg/dL Standard Error 8

SECONDARY outcome

Timeframe: Measured at baseline and Month 12

Population: All available data (all participants for whom change from baseline to 12 months was available)

Overnight frequent sampling of growth hormone levels was performed and characteristics of pulsatile secretion were determine using automated deconvolution (using AutoDecon software). Based on the deconvolution, the median pulse mass (in nanograms per millileter of growth hormone) was calculated. A positive number indicates an increase in median pulse mass between baseline and 12 months.

Outcome measures

Outcome measures
Measure	TH9507 n=18 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). TH9507: Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months.	Placebo n=12 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Change in Growth Hormone Pulse Characteristics (Median Pulse Mass) as Assessed by Overnight Frequent Sampling of Growth Hormone	0.54 nanograms/milliliter Standard Deviation 1.35	0.20 nanograms/milliliter Standard Deviation 0.30

SECONDARY outcome

Timeframe: Measured at Baseline and Month 12

Population: All available data. Assessment of mitochondrial function could not be performed in all patients.

Change in post-exercise phosphocreatine recovery \[ViPCr\] between baseline and 12 months (positive change indicates increase in the variable between baseline and 12 months). ViPCR is the initial rate of phosphocreatine recovery normalized based on participant effort. Greater ViPCr represents relatively better mitochondrial function.

Outcome measures

Outcome measures
Measure	TH9507 n=9 Participants Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). TH9507: Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months.	Placebo n=11 Participants Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Mitochondrial Function (Post-exercise Phosphocreatine Recovery [ViPCr]) by 31P-MRS	0.01 milliMoles/second Standard Deviation 11.3	-1.02 milliMoles/second Standard Deviation 5.7

Adverse Events

TH9507

Serious events: 0 serious events

Other events: 28 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 26 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Steven K. Grinspoon MD

Massachusetts General Hospital

Phone: 617-726-3890

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	TH9507 n=31 participants at risk Participants received treatment with growth hormone releasing hormone 1-44 (TH9507). Growth hormone releasing hormone (GHRH) 1-44 : 2-mg sub-cutaneous abdominal injections once daily for 12 months	Placebo n=29 participants at risk Participants received treatment with placebo medication. Placebo: 2-mg sub-cutaneous abdominal injections once daily for 12 months
Musculoskeletal and connective tissue disorders Arthralgia	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Injection site bruising	54.8% 17/31 • Number of events 17 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	72.4% 21/29 • Number of events 21 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Cardiac disorders Hypertension	25.8% 8/31 • Number of events 8 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	17.2% 5/29 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Injection-site bleeding	12.9% 4/31 • Number of events 4 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	17.2% 5/29 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Injection-site pain	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Metabolism and nutrition disorders Hyperglycemia	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Nervous system disorders Tingling/ Paresthesia	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Vascular disorders Peripheral edema	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Injection site puritis	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Injection site reaction	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Injection site erythema	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Psychiatric disorders Anxiety	3.2% 1/31 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	10.3% 3/29 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Gastrointestinal disorders Abdominal pain	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	10.3% 3/29 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Psychiatric disorders Atypical chest pain	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Musculoskeletal and connective tissue disorders Back pain	12.9% 4/31 • Number of events 4 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	13.8% 4/29 • Number of events 4 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Gastrointestinal disorders Constipation	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Psychiatric disorders Depression	0.00% 0/31 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Skin and subcutaneous tissue disorders Dermatitis	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Gastrointestinal disorders Diarrhea	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Nervous system disorders Fatigue	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Infections and infestations Fungal infection	0.00% 0/31 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	10.3% 3/29 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Gastrointestinal disorders Gastroenteritis	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	3.4% 1/29 • Number of events 1 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Gastrointestinal disorders Gastroesophageal reflux disease	0.00% 0/31 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Nervous system disorders Headache	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	17.2% 5/29 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Infections and infestations Infection	0.00% 0/31 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
General disorders Mechanical injury	0.00% 0/31 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	10.3% 3/29 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Musculoskeletal and connective tissue disorders Musculoskeletal injury	16.1% 5/31 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	17.2% 5/29 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	12.9% 4/31 • Number of events 4 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	17.2% 5/29 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Musculoskeletal and connective tissue disorders Myalgia	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	10.3% 3/29 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Infections and infestations Nasopharyngitis	0.00% 0/31 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	6.9% 2/29 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Gastrointestinal disorders Nausea	9.7% 3/31 • Number of events 3 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Infections and infestations Sinusitis	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	20.7% 6/29 • Number of events 6 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Musculoskeletal and connective tissue disorders Tendonitis	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
General disorders Toothache	6.5% 2/31 • Number of events 2 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	0.00% 0/29 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.
Infections and infestations Upper respiratory tract infection	16.1% 5/31 • Number of events 5 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.	24.1% 7/29 • Number of events 7 • Safety visits occurred at 2 weeks, 1, 3, 6 and 9 months at which time fasting glucose and IGF-1 were monitored.