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

May 2, 2012 updated by: Kevin Yuen, Oregon Health and Science University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: B
Placebo
Drug: Placebo
Placebo self-injected once a day subcutaneously at bedtime.
Other Names:
  • Placebo.
Active Comparator: A
Growth hormone
Drug: Growth hormone (Genotropin)
Growth hormone 0.1 mg self-injected once a day subcutaneously at bedtime.
Other Names:
  • Genotropin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp
Time Frame: 3 months
3 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Changes in fat IGF-I and IGF-I/insulin hybrid receptor density and body composition.
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oregon Health and Science University

Investigators

  • Principal Investigator: Jonathan Q. Purnell, MD, Oregon Health and Science University
  • Principal Investigator: Charles T. Roberts, PhD, Oregon Health and Science University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2006

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

January 1, 2012

Study Registration Dates

First Submitted

August 15, 2007

First Submitted That Met QC Criteria

August 15, 2007

First Posted (Estimate)

August 16, 2007

Study Record Updates

Last Update Posted (Estimate)

May 3, 2012

Last Update Submitted That Met QC Criteria

May 2, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB1844

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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