Aging, Hormone Deficiency
Conditions
Keywords
Growth Hormone Releasing Hormone, Growth Hormone Insufficiency, Aging, Growth Hormone, Physiologic Effects of Drugs, Hormones, Hormone Substitutes, and Hormone Antagonists, Hormones
Brief summary
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
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.
Interventions
DRUGGrowth Hormone Releasing Hormone (GHRH )
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
Sponsors
National Institute on Aging (NIA)
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Muscle Strength | 12 weeks | Pre-drug and post-drug 1 RM (Repetition Maximum) testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Glucose Homeostasis | 12 weeks | Glucose clamp study at week 12 of study drug use |
| Fat-free and Lean Mass | baseline and 12 weeks | iDXA scan |
| Fuel Utilization | baseline and 12 weeks | Assessment of resting metabolic rate |
| Physical Performance | Baseline and 12 weeks | 6 Minute Walk Test |
| Tolerability of Nocturnal Administration | Ongoing throughout 12 weeks | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Growth Hormone Releasing Hormone (GHRH) Drug: GHRH
Growth Hormone Releasing Hormone (GHRH ): 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 | 13 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | PI decision | 13 |
Baseline characteristics
| Characteristic | Growth Hormone Releasing Hormone (GHRH) | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 13 Participants | — |
| Age, Categorical Between 18 and 65 years | 0 Participants | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 13 Participants | — |
| Sex/Gender, Customized Male or Female | NA Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 1 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Muscle Strength
Pre-drug and post-drug 1 RM (Repetition Maximum) testing
Time frame: 12 weeks
Population: Study was terminated, no data collected.
Secondary
Fat-free and Lean Mass
iDXA scan
Time frame: baseline and 12 weeks
Population: Study was terminated, no data collected.
Secondary
Fuel Utilization
Assessment of resting metabolic rate
Time frame: baseline and 12 weeks
Population: Study was terminated, no data collected.
Secondary
Glucose Homeostasis
Glucose clamp study at week 12 of study drug use
Time frame: 12 weeks
Population: Study was terminated, no data collected.
Secondary
Physical Performance
6 Minute Walk Test
Time frame: Baseline and 12 weeks
Population: Study was terminated, no data collected.
Secondary
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.
Time frame: Ongoing throughout 12 weeks
Population: Study was terminated, no data collected.