Growth Hormone Administration and the Human Immune System

Objectives and Specific Aims:

We plan to investigate whether growth hormone, administered in a physiological or pulsatile fashion, can elicit relevant changes in the human immune system while at the same time associated with no change or even an improvement in the metabolic profiles such as insulin sensitivity.

Experimental Design and Methods:

Thirty-eight healthy men, age 25-50, will be recruited for this study. There are three parts to this study: Study I, Study IB and Study II. Study I and IB each involve six subjects and are designed to test the hypothesis that pulsatile subcutaneous infusion of GH via a subcutaneous infusion pump yields a reasonable pulsatile GH pattern. The dose of GH used in Study IB is three-fold higher than in Study I. Study I and IB are done first before proceeding to Study II.

Study II is a randomized, double-blinded, placebo-controlled 12-week study involving 26 subjects divided into 2 groups: Group A and Group B. Group A involves 13 subjects receiving pulsatile GH or placebo infusion for 4 weeks with 8-week washout after intervention. Group B involves 13 subjects receiving conventional once a day subcutaneous infusion of GH or placebo for 4 weeks with 8-week washout after intervention.

Medical Relevance and Expected Outcome:

This study ascertains the significance of the effect of pulsatile growth hormone administration on the human immune system and metabolic profile.

• INCLUSION CRITERIA:

• Healthy men only (There is a gender difference in GH response with adult females requiring on average twice the GH dose for similar effects. In order to eliminate gender difference as a confounding factor in this study, we are studying male subjects only because the GH dose requirement is lower.)
• Age 25-50 (Age restriction is used to remove age as a confounding factor because GH and thymic function are known to decrease with age.)
• Screening laboratory evaluations with no clinically significant abnormal results (minor deviations from "normal" lab results will be at the discretion of the principal investigator):

• fasting comprehensive metabolic panel
• complete blood count with differential and platelets
• 75-gram oral glucose tolerance test (OGTT)

• fasting plasma glucose (FPG) < 100 mg/dL
• 2-hr OGTT < 140 mg/dL
• Insulin-like growth factor-I (IGF-I)
• thyroid function test (TSH, free T3, free T4)
• fasting lipid profile
• BMI < 30 (Men with BMI >= 30 are excluded because decrease in GH secretion and clearance has been shown in obesity.)
• Have NOT participated in another clinical trial involving any pharmacologic agents within the past 60 days
• Able to complete an inform consent
• Agree to not participate in other clinical trials within the study period

Exclusion criteria

• Women
• FPG >= 100 mg/dL or 2-hour OGTT >= 140 mg/dL
• Abnormal electrocardiogram (EKG) suggesting possible underlying cardiac conditions that, in the opinion of the investigator(s), may cause participation of the subject in the study unsafe
• Positive stool guaiac
• Evidence of illicit drug use
• History of smoking any tobacco products within one year prior to screening
• Alcohol intake > 30 grams (drink more than 2 beers per day OR equivalent amount of alcohol)
• History of Human Immunodeficiency Virus (HIV) infection
• History of active or chronic Hepatitis B and/or C infection
• History of malignancy
• History of coronary disease
• History of seizures or other neurologic diseases
• History of liver or renal diseases
• History of gastrointestinal or endocrine disorders
• History of glucocorticoid use (over one month) or other immunosuppressive agents (any)
• unable to undergo a magnetic resonance imaging (MRI) procedure
• Any medical history that, in the opinion of the investigator(s), will make participation of the subject in the study unsafe