Three Month Treatment of Growth Hormone Releasing Hormone (GHRH) in the Elderly

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the effect of a naturally occurring hormone, called Growth Hormone Releasing Hormone (GHRH) on the muscle, bone, and fat tissues of the body. GHRH stimulates the production of growth hormone (GH), which regulates the build up of many tissues in the body, including muscles and bones. Many elderly people have low levels of GH. The overall goal of this research is to determine the efficacy of GHRH to raise levels of GH and improve these body tissues. Healthy men and women age 65 and older will receive GHRH in four doses nightly for 12 weeks and assessed for changes in muscle strength, body mass, physical performance, and how the body uses sugar.

Detailed Description
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Although multiple factors appear to be associated with the functional deterioration of advanced age, decreases in muscle mass and strength (sarcopenia) are commonly seen in aging subjects and are major risk factors for subsequent disability. There are many potential causes of sarcopenia and functional impairment in the elderly, including medical conditions such as cardiovascular disease, altered mood, and sedentary lifestyle. Hyposomatotropism, or decreased activity of growth hormone (GH), is one factor that has been implicated. GH is a major anabolic hormone that exerts important stimulatory effects on protein synthesis. Many of the peripheral tissue effects of GH are mediated by insulin-like growth factor 1 (IGF-1) produced systemically by the liver or locally in tissues in response to GH stimulation. IGF-1, in turn, regulates GH secretion by negative feedback mechanisms at the pituitary gland. Several investigators have shown that aging is associated with a decrease in spontaneous GH secretion and IGF-1 levels. GH levels decline by 14% for each decade after puberty. Reduction of GH release in aging is thought to be associated with an increase in somatostatin tone, decrease in hypothalmic GHRH output, and diminished response to GHRH. The fact that aging is accompanied by a decrease in protein synthesis leading to a loss of lean body mass and a gain in body fat suggests that a decrease in GH secretion may contribute to these changes. It has been hypothesized that restoration of GH level in the elderly to the levels observed in younger individuals may lead to improvements in body composition. GH may also increase slow wave (delta or deep) sleep in older adults.

Official Title
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Three Month Treatment of GHRH (Growth Hormone Releasing Hormone) in the Elderly

Conditions
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Aging, Hormone Deficiency

Intervention / Treatment
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* Drug: Growth Hormone Releasing Hormone (GHRH )


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 65 years or older Fasting IGF-1 level <135ng/ml BMI 23-40 kg/m2 Capable of giving informed consent Exclusion Criteria: Diabetes mellitus or use of hypoglycemic agents Known coronary artery disease Liver disease, abnormal liver function tests (LRTs>2x upper limit of normal) or inflammatory bowel disease Renal insufficiency (serum creatinine > or = to 1.4 mg/dL) Hematocrit < 33% or > 50% History of malignancy < 5 years other than basal cell of the skin Chronic pulmonary disease or other systemic disorders which affect glucose hemostasis Use of growth hormone, corticosteroids, thiazide diuretics, estrogen supplements or androgen supplements Inability to perform strength or performance testing Uncontrolled hypertension (blood pressure >160/95 NYHA Class III or IV heart failure Current smoking Alcohol use > or = to 30g/day Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study Participation in an investigational drug study within 6 weeks prior to screening visit Plan to change diet or exercise regimen during the study period

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Growth Hormone Releasing Hormone (GHRH)<br>Drug: GHRH | Drug: Growth Hormone Releasing Hormone (GHRH )<br>* GHRH administered subcutaneously at 2.0 mg/kg/dose bolus each night at 11:00 PM, 1:00 AM, 3:00 AM, and 5:00 AM for 12 weeks<br>* Other names: Growth Hormone Releasing Factor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle Strength | Pre-drug and post-drug 1 RM (Repetition Maximum) testing | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glucose Homeostasis | Glucose clamp study at week 12 of study drug use | 12 weeks | 
| Fat-free and Lean Mass | iDXA scan | baseline and 12 weeks | 
| Fuel Utilization | Assessment of resting metabolic rate | baseline and 12 weeks | 
| Physical Performance | 6 Minute Walk Test | Baseline and 12 weeks | 
| Tolerability of Nocturnal Administration | Subjects record diary of drug administration in evening and morning describing any issues with pump system for drug delivery, local skin issues at site of injection or other adverse events. Study nurses also record telephone contact with subjects every other day for first week of dosing and weekly for first month. | Ongoing throughout 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Growth Hormone Releasing Hormone, Growth Hormone Insufficiency, Aging, Growth Hormone, Physiologic Effects of Drugs, Hormones, Hormone Substitutes, and Hormone Antagonists, Hormones