Effectiveness of Growth Hormone Releasing Hormone in Reducing Abdominal Fat in People Who Are Obese
|Abdominal Obesity Growth Hormone Deficiency||Drug: Growth hormone releasing hormone (GHRH) 1-44 Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Physiologic Effects of Long-Term GHRH1-44 in Abdominal Obesity|
- Change in Visceral Adipose Tissue Volume [ Time Frame: Measured at baseline and Months 6 and 12 ]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.
- Change in Carotid Intima-media Thickness [ Time Frame: 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.
- Change in Lipid Profile (Total Cholesterol, High-density Lipoproteins [HDL] Cholesterol, Low-density Lipoproteins [LDL] Cholesterol, Triglycerides) [ Time Frame: 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.
- Change in Glucose Tolerance as Measured by Oral Glucose Tolerance Test [ Time Frame: 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.
- Change in Growth Hormone Pulse Characteristics as Assessed by Overnight Frequent Sampling of Growth Hormone [ Time Frame: Measured at baseline and Month 12 ]Analysis ongoing, no data available currently.
- Mitochondrial Function by 31P-MRS [ Time Frame: Measured at Baseline and Months 6 and 12 ]Analysis ongoing, no data available currently.
|Study Start Date:||July 2008|
|Study Completion Date:||January 2012|
|Primary Completion Date:||January 2012 (Final data collection date for primary outcome measure)|
Participants will receive treatment with growth hormone releasing hormone 1-44 (TH9507).
Drug: Growth hormone releasing hormone (GHRH) 1-44
2-mg sub-cutaneous injections once daily for 12 months
Other Name: TH9507
Placebo Comparator: 2
Participants will receive treatment with placebo medication.
2-mg sub-cutaneous injections once daily for 12 months
Obesity, defined as having a high amount of excess body fat, is one of the most wide-spread health problems of today. A variety of factors can lead to obesity. These factors include physical inactivity, family history and genetics, metabolism, and hormone imbalance. The excess body fat in obesity increases a person's risk of a number of life-threatening diseases, including heart disease, gall stones, type 2 diabetes, and certain types of cancer. People with abdominal obesity, where fat is stored predominantly around a person's midsection, are particularly prone to weight-related diseases. Studies have shown that administration of growth hormone to obese people reduces abdominal fat, but can be associated with adverse side effects. GHRH is a natural hypothalamic peptide that stimulates growth hormone release. GHRH may be able to normalize growth hormone levels, reduce abdominal fat, and lessen risk for cardiovascular disease in people who are obese, without the associated side effects of growth hormone administration. However, further study is needed on GHRH. This study will evaluate the safety and effectiveness of synthetic GHRH in decreasing the amount of abdominal fat and improving cardiovascular function in people who are obese.
Participation is this study will last 1 year from screening and will include 9 study visits. During Visit 1, participants will undergo screening tests that will include a medical history, a physical exam, body measurements, a blood draw, a urine test, a GHRH+Arginine stimulation test, an electrocardiogram (ECG), and a test for the presence of blood in stool. Eligible participants will return within the next 3 weeks for an inpatient clinic stay for Visit 2. Participants will be asked to keep a food record of all food consumed during the 4 days before the second visit. Visit 2 will include a physical exam, a medical and smoking history, a review of current medications, body measurements, an overnight blood draw, a body metabolism evaluation, an oral glucose tolerance test, and two questionnaires. Also during Visit 2, participants will be assigned randomly to treatment with active GHRH or placebo. Participants will then be taught how to give themselves injections of the study drug, which will be taken daily for 12 months. Participants will also receive a 1-month supply of study drug and will be supplied with refills in subsequent study visits. Upon starting treatment, participants will undergo more testing, including a whole body DEXA scan, abdominal computed tomography (CT) scan, carotid ultrasound, and ECG.
Visit 3 will occur at Week 2 of treatment and will include a review of study medications, questions about any side effects experienced, vital sign measurements, a blood draw, an ECG, and, if female, a urine test. Visits 4, 5, and 7 will be identical to Visit 3 and will occur at Months 1, 3, and 9 respectively. Visit 6 will occur at Month 6 and will be identical to Visit 2 but without the overnight blood draw. Visit 8 will occur at Month 12 and will be identical to Visit 2, except no further study drug will be dispensed. At Month 13, participants will complete the final study visit, which will include repeat tests from Visit 1.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00675506
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Steven K. Grinspoon, MD||Massachusetts General Hospital|