Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates
Condition: Growth Hormone Deficiency
MeSH terms: Insulin Resistance; Hypersensitivity
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Study hypothesis:

      Growth hormone (GH), through its generation of free 'bioavailable' insulin-like growth factor
      (IGF)-I, can improve insulin sensitivity in adults with GH deficiency.

      Study aims:

      The purpose of this study is to determine the mechanism of how low dose GH treatment affects
      the body's sensitivity to insulin actions and whether this low GH dose can affect the body's
      handling of steroid hormone levels (cortisol clearance) in adults with GH deficiency.

      Study design:

      Men and women with confirmed GH deficiency, but not recently been on GH treatment will be
      invited to participate in this study. The subjects will be assessed at the initial visit to
      ascertain their suitability before further participating in the study. If suitable, an equal
      number of men and women will be randomized to receive either low dose GH or placebo injection
      for 3 months. Before, during and after treatment, the subjects will be assessed at regularly
      with blood tests, scans and fat biopsies. At the first and final visit, testing will include
      scans to measure the amount of whole body fat and fat in the stomach area, muscle, and liver;
      blood tests to measure levels of cortisol, and fat tissue (taken from a biopsy) analysis to
      measure the density of IGF-I in the muscle; whereas blood tests to examine insulin
      sensitivity will also be collected. This study will use Genotropin and Genotropin pen
      devices, and the the data will be analyzed using a computer statistical program where the
      identity of the subjects will be coded to maintain confidentiality.
    

Detailed description: 
      The study will be double-blinded. One hundred subjects will be screened for eligibility
      initially, and 24 subjects will be enrolled with 12 subjects being randomized to receive the
      low GH dose (0.1 mg/day) treatment and 12 subjects to receive Placebo treatment for 3 months,
      allowing a 10% drop-out rate. The subjects will be taught by either by the Endocrine Nurse
      Specialists to self-administer the GH by subcutaneous injections using a Genotropin pen
      device.

      Visit 1, Initial Screening Assessment (as out-patient)

        -  Physical examination, weight, height, and waist circumference measurements

        -  Fasting blood glucose levels

      Visit 2, Baseline Assessment (as in-patient)

        -  Physical examination, weight, height, and waist circumference measurements

        -  Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2,
           IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles

        -  MRS, abdominal CT and DEXA scans

        -  One-step 3-hour hyperinsulinaemic euglycaemic clamp

        -  Cortisol production rates and urine cortisol collections

        -  Fat biopsies will be taken at the end of the assessment of cortisol production rates

      Visit 3, Interim Assessment (Month 1) (as out-patient)

        -  Documentation of any adverse effects

        -  Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2,
           IGFBPs -1 and -3

      Visit 4, Final Assessment (Month 3) (as in-patient)

        -  Physical examination, weight, height, and waist circumference measurements

        -  Fasting blood tests for glucose, insulin, C-peptide, free IGF-I, total IGF-I, IGF-2,
           IGFBPs -1 and -3, non-esterified fatty acid and lipid profiles

        -  MRS, abdominal CT and DEXA scans

        -  One-step 3-hour hyperinsulinaemic euglycaemic clamp

        -  Cortisol production rates and urine cortisol collections

        -  Fat biopsies will be taken at the end of the assessment of cortisol production rates

      Any extra blood remaining from the samples of blood drawn may be banked indefinitely with
      confidential identifiers, and may be given to researchers in the future to examine for other
      potential causes of diabetes and heart diseases in adults. These blood samples, however, will
      not be used for genetic studies.
    

Intervention name(s): Growth hormone (Genotropin); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Growth hormone 0.1 mg self-injected once a day subcutaneously at bedtime.; Placebo self-injected once a day subcutaneously at bedtime.
Other intervention name(s): Genotropin; Placebo.
Intervention MeSH terms: Hormones
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Growth hormone; insulin sensitivity; cortisol