Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates

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Brief Title

Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates

Official Title

Effects of Low Dose Growth Hormone (GH) Therapy on Insulin Sensitivity, Adipocyte Insulin-like Growth Factor-I (IGF-I) and IGF-I/Insulin Receptor Density and Regulation of Cortisol Metabolism in GH Deficient Adults

Brief 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.
    

Study Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp

Secondary Outcome

 Changes in fat IGF-I and IGF-I/insulin hybrid receptor density and body composition.

Condition

Growth Hormone Deficiency

Intervention

Growth hormone (Genotropin)

Study Arms / Comparison Groups

 A
Description:  Growth hormone

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

16

Start Date

January 2006

Completion Date

January 2012

Primary Completion Date

January 2012

Eligibility Criteria

        Inclusion Criteria:

          -  Age range 18 to 75 years

          -  BMI should not exceed 40 kg/m2

          -  Confirmed GH deficient with at least one provocative test, e.g. insulin tolerance test
             and/ or GHRH/arginine

          -  Not received any GH therapy within last 6 months

          -  On a stable standardized hydrocortisone replacement dose regimen (twice a day at 8 AM
             and 4 PM),

          -  If any other pituitary hormone deficiencies are present, patient must be on optimal
             pituitary hormone replacement therapy, e.g. Thyroxine, testosterone and oestrogen
             replacement

          -  Normal renal and hepatic function

          -  Prepared to self-inject

        Exclusion Criteria:

          -  Untreated or subclinically hypo/hyperthyroid

          -  Untreated or subclinically treated hypocortisolism

          -  Type 1 or 2 diabetes mellitus

          -  Subjects with evidence of nephropathy from any cause

          -  Subjects with evidence of retinopathy from any cause

          -  Any other medical illnesses that may affect the interpretation of the results

          -  Pregnant

          -  Emotional/social instability likely to prejudice study completion

          -  Previous history of known malignancy

          -  Recurrent or severe unexplained hypoglycaemia

          -  Known or suspected drug/alcohol abuse
      

Gender

All

Ages

18 Years - 75 Years

Accepts Healthy Volunteers

No

Contacts

Jonathan Q. Purnell, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00517062

Organization ID

IRB1844


Responsible Party

Principal Investigator

Study Sponsor

Oregon Health and Science University


Study Sponsor

Jonathan Q. Purnell, MD, Principal Investigator, Oregon Health and Science University


Verification Date

May 2012