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

• Muscle strength [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  Pre-drug and post-drug 1 RM (Repetition Maximum) testing
  
  

• Glucose homeostasis [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  Glucose clamp study at week 12 of study drug use
  
  
• Fat-free and lean mass [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  iDXA scan
  
  
• Fuel utilization [ Time Frame: baseline and 12 weeks ] [ Designated as safety issue: No ]
  Assessment of resting metabolic rate
  
  
• Physical performance [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]
  6 Minute Walk Test
  
  
• Tolerability of nocturnal administration [ Time Frame: Ongoing throughout 12 weeks ] [ Designated as safety issue: Yes ]
  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.
  
  

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.