Low Dose Growth Hormone (GH) on Insulin Sensitivity and Cortisol Production Rates - Full Text View

Sponsor:	Oregon Health and Science University
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00517062

Purpose

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.

Condition	Intervention	Phase
Growth Hormone Deficiency	Drug: Growth hormone (Genotropin) Drug: Placebo	Phase 0

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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

Resource links provided by NLM:

Further study details as provided by Oregon Health and Science University:

Primary Outcome Measures:

Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Changes in fat IGF-I and IGF-I/insulin hybrid receptor density and body composition. [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	January 2006
Estimated Study Completion Date:	March 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: A Growth hormone	Drug: Growth hormone (Genotropin) Growth hormone 0.1 mg self-injected once a day subcutaneously at bedtime. Other Name: Genotropin
Placebo Comparator: B Placebo	Drug: Placebo Placebo self-injected once a day subcutaneously at bedtime. Other Name: Placebo.

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.

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00517062

Contacts

Contact: Kevin C. Yuen, MD, MRCP(UK)	503 494 0175	yuenk@ohsu.edu
Contact: David M. Cook, MD	503 494 3713	cookd@ohsu.edu

Locations

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

Sponsors and Collaborators

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

More Information

Additional Information:

American Endocrine Society This link exits the ClinicalTrials.gov site

Publications:

Yuen KC, Frystyk J, White DK, Twickler TB, Koppeschaar HP, Harris PE, Fryklund L, Murgatroyd PR, Dunger DB. Improvement in insulin sensitivity without concomitant changes in body composition and cardiovascular risk markers following fixed administration of a very low growth hormone (GH) dose in adults with severe GH deficiency. Clin Endocrinol (Oxf). 2005 Oct;63(4):428-36. Erratum in: Clin Endocrinol (Oxf). 2005 Nov;63(5):599.

Yuen K, Frystyk J, Umpleby M, Fryklund L, Dunger D. Changes in free rather than total insulin-like growth factor-I enhance insulin sensitivity and suppress endogenous peak growth hormone (GH) release following short-term low-dose GH administration in young healthy adults. J Clin Endocrinol Metab. 2004 Aug;89(8):3956-64.

Yuen K, Wareham N, Frystyk J, Hennings S, Mitchell J, Fryklund L, Dunger D. Short-term low-dose growth hormone administration in subjects with impaired glucose tolerance and the metabolic syndrome: effects on beta-cell function and post-load glucose tolerance. Eur J Endocrinol. 2004 Jul;151(1):39-45.

Responsible Party:	Kevin Yuen, MD, Oregon Health & Science University
ClinicalTrials.gov Identifier:	NCT00517062 History of Changes
Other Study ID Numbers:	IRB1844
Study First Received:	August 15, 2007
Last Updated:	July 23, 2008
Health Authority:	United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:

Growth hormone
insulin sensitivity
cortisol

Additional relevant MeSH terms:

Dwarfism, Pituitary
Endocrine System Diseases
Insulin Resistance
Dwarfism
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Bone Diseases, Endocrine
Hypopituitarism
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases

Nervous System Diseases
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hormones
Insulin
Hydrocortisone
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Hypoglycemic Agents
Anti-Inflammatory Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012