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

Oregon Health & Science University (OHSU)

Status and phase

Completed

Early Phase 1

Conditions

Growth Hormone Deficiency

Treatments

Drug: Placebo

Drug: Growth hormone (Genotropin)

Study type

Interventional

Funder types

Other

Identifiers

NCT00517062

IRB1844

Details and patient eligibility

About

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.

Full 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.

Enrollment

16 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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