Low Dose Growth Hormone in Obese PCOS Women

NCT00518635 | Withdrawn

• 1 other identifier: IRB3711
• Study Type: interventional
• Target: N/A
• 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 and the metabolic profile of women with polycystic ovary syndrome. Study aims: 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) and testosterone (male hormones) in obese women with polycystic ovary syndrome. Study design: Obese women with polycystic ovary syndrome, but not recently been on GH treatment, and presently attending Outpatients Clinic 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 women will be randomized to receive either daily low dose GH or placebo injections first for 12 weeks, before exchanging over for another 12 weeks of treatment after a 4-week washout period. Before, during and after treatment, the subjects will be assessed at frequently with blood tests, scans and fat biopsies. During the study, the subjects will be studied 4 times at the Oregon Clinical and Translational Research Institute (OCTRI). At the first, second 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 insulin-like growth factor-I (a hormone stimulated by growth hormone in the body) in fat; whereas blood tests to examine how well insulin works in the body (insulin sensitivity) will be collected at all visits of the study.

Conditions

Polycystic Ovary Syndrome

Keywords

Growth hormone; Insulin sensitivity; Polycystic ovary

Outcome Measures

Primary Outcomes (1)

• Changes in insulin sensitivity, and adipocyte IGF-I and insulin receptor signaling.

  24 months

Secondary Outcomes (1)

• Changes in body composition, cortisol production rates, and muscle and liver intramyocellular content.

  24 months

Study Arms (1)

A

EXPERIMENTAL

Growth hormone or Placebo 0.1 mg/day self-administrated once a day.

Drug: Nutropin

Interventions

Nutropin DRUG

Nutropin 0.1 mg/day self-administered once a day

Also known as: Growth hormone, PCOS, insulin sensitivity

A

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Ability to provide written informed consent and comply with study assessments for the full duration of the study.
• Age 21 to 45 years
• Body mass index between 30 to 40 kg/m2
• Diagnosis of PCOS with underlying insulin resistance (assessed by HOMA at screening visit) and/or other features that characterizes the metabolic syndrome such as hypertension ( \> 130/85 mmHg), abdominal obesity (waist circumference \> 88 cm), and acanthosis nigricans
• Diagnosis of normal or impaired glucose tolerance (WHO criteria)
• Stable body weight for at least 6 months prior to study entry (body weight deviating +/- 5 kg from previously recorded weight \> 6 months ago)
• Normal thyroid, renal and hepatic function
• Able to self administer daily GH/Placebo injections

You may not qualify if:

• Inability to comply with study requirements
• Body mass index \< 30 kg/m2 and \> 40 kg/m2 (patients with body mass index \> 40 kg/m2 are excluded because they will not fit into the MRS scanner)
• Untreated hypothyroidism or hyperthyroidism
• Anemia from any cause
• Known diabetes mellitus
• Patients with an increased risk of venous thrombosis or previous history of recurrent venous thrombosis
• Patient on any insulin-sensitizers (e.g., Metformin, Rosiglitazone, Pioglitazone) within 30 days of screening assessment
• Patient on any anti-androgens (e.g., Spironolactone, Cyproterone acetate, Flutamide, Finasteride) within 30 days of screening assessment
• Patient with other concurrent illnesses
• Pregnant (positive pregnancy test) prior enrollment in the study or planning to conceive whilst participating in the study
• Emotional/social instability likely to prejudice study completion
• Previous history of known malignancy
• Recurrent or severe unexplained hypoglycemia
• Known or suspected drug/alcohol abuse
• Patient with any metals in the body

Sponsors & Collaborators

• Oregon Health and Science University: lead

Study Sites (1)

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Related Publications (8)

• Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004 Jun;89(6):2745-9. doi: 10.1210/jc.2003-032046.

  PMID: 15181052 BACKGROUND

• Carmina E, Lobo RA. Polycystic ovary syndrome (PCOS): arguably the most common endocrinopathy is associated with significant morbidity in women. J Clin Endocrinol Metab. 1999 Jun;84(6):1897-9. doi: 10.1210/jcem.84.6.5803. No abstract available.

  PMID: 10372683 BACKGROUND

• de Boer JA, Lambalk CB, Hendriks HH, van Aken C, van der Veen EA, Schoemaker J. Growth hormone secretion is impaired but not related to insulin sensitivity in non-obese patients with polycystic ovary syndrome. Hum Reprod. 2004 Mar;19(3):504-9. doi: 10.1093/humrep/deh122. Epub 2004 Jan 29.

  PMID: 14998943 BACKGROUND

• Van Dam EW, Roelfsema F, Helmerhorst FH, Frolich M, Meinders AE, Veldhuis JD, Pijl H. Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome. J Clin Endocrinol Metab. 2002 Sep;87(9):4225-30. doi: 10.1210/jc.2002-012006.

  PMID: 12213875 BACKGROUND

• Essah PA, Nestler JE. Metabolic syndrome in women with polycystic ovary syndrome. Fertil Steril. 2006 Jul;86 Suppl 1:S18-9. doi: 10.1016/j.fertnstert.2006.04.013.

  PMID: 16798277 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, 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

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Insulin Resistance

Interventions

Human Growth Hormone; Growth Hormone; Insulin

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; 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; Proinsulin; Insulins; Pancreatic Hormones

Study Officials

• Kevin C. Yuen, MRCP(UK), MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

• David M. Cook, MD

  Oregon Health and Science University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor in Endocrinology

Study Record Dates

• First Submitted: August 17, 2007
• First Posted: August 21, 2007
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: February 20, 2013

Record last verified: 2013-02

Locations

US (1)