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

NCT00517062 | Completed Early Phase 1 DMC

• 1 other identifier: IRB1844
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Growth Hormone Deficiency

Keywords

Growth hormone; insulin sensitivity; cortisol

Outcome Measures

Primary Outcomes (1)

• Changes in insulin sensitivity (from the hyperinsulinemic euglycemic clamp

  3 months

Secondary Outcomes (1)

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

  3 months

Study Arms (2)

A

ACTIVE COMPARATOR

Growth hormone

Drug: Growth hormone (Genotropin)

B

PLACEBO COMPARATOR

Placebo

Drug: Placebo

Interventions

Growth hormone (Genotropin) DRUG

Growth hormone 0.1 mg self-injected once a day subcutaneously at bedtime.

Also known as: Genotropin

A

Placebo DRUG

Placebo self-injected once a day subcutaneously at bedtime.

Also known as: Placebo.

B

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Oregon Health and Science University: lead

Study Sites (1)

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Related Publications (4)

• 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. doi: 10.1111/j.1365-2265.2005.02359.x.

  PMID: 16181235 BACKGROUND

• 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. doi: 10.1210/jc.2004-0300.

  PMID: 15292333 BACKGROUND

• 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. doi: 10.1530/eje.0.1510039.

  PMID: 15248820 BACKGROUND

• Yuen KC, Roberts CT Jr, Frystyk J, Rooney WD, Pollaro JR, Klopfenstein BJ, Purnell JQ. Short-term, low-dose GH therapy improves insulin sensitivity without modifying cortisol metabolism and ectopic fat accumulation in adults with GH deficiency. J Clin Endocrinol Metab. 2014 Oct;99(10):E1862-9. doi: 10.1210/jc.2014-1532. Epub 2014 Jul 11.

  PMID: 25013996 DERIVED

Related Links

• American Endocrine Society

MeSH Terms

Conditions

Dwarfism, Pituitary; Insulin Resistance

Interventions

Growth Hormone; Human Growth Hormone

Condition Hierarchy (Ancestors)

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; Endocrine System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Anterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Jonathan Q. Purnell, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

• Charles T. Roberts, PhD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 15, 2007
• First Posted: August 16, 2007
• Study Start: January 1, 2006
• Primary Completion: January 1, 2012
• Study Completion: January 1, 2012
• Last Updated: May 3, 2012

Record last verified: 2012-05

Locations

US (1)