Low Dose Growth Hormone in Obese PCOS Women - Full Text View

Sponsor:	Oregon Health and Science University
Information provided by:	Oregon Health and Science University
ClinicalTrials.gov Identifier:	NCT00518635

Purpose

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.

Condition	Intervention
Polycystic Ovary Syndrome	Drug: Nutropin

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Effects of Low Dose Growth Hormone (GH) Therapy on Insulin Sensitivity, Metabolic Profile, Adipocyte IGF-I and Insulin Signaling, Intramyocellular Lipids, and Cortisol Metabolism in Obese Women With Polycystic Ovary Syndrome (PCOS)

Resource links provided by NLM:

MedlinePlus related topics: Obesity

Drug Information available for: Insulin Somatropin Somatotropin

U.S. FDA Resources

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

Primary Outcome Measures:

Changes in insulin sensitivity, and adipocyte IGF-I and insulin receptor signaling. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Changes in body composition, cortisol production rates, and muscle and liver intramyocellular content. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	12
Study Start Date:	May 2008
Estimated Study Completion Date:	August 2010
Estimated Primary Completion Date:	May 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental Growth hormone or Placebo 0.1 mg/day self-administrated once a day.	Drug: Nutropin Nutropin 0.1 mg/day self-administered once a day

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Eligibility

Ages Eligible for Study:	21 Years to 45 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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
Any other condition/s that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
Participation in another simultaneous medical investigation or trial

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00518635

Contacts

Contact: Kevin C. Yuen, MRCP(UK), MD	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
Contact: Kevin C. Yuen, MD 503-494-0175 yuenk@ohsu.edu
Contact: Stacy Legg, BA 503 494 5317 leggs@ohsu.edu
Oregon Health and Science University	Recruiting
Portland, Oregon, United States, 97239

Sponsors and Collaborators

Oregon Health and Science University

Investigators

Principal Investigator:	Kevin C. Yuen, MRCP(UK), MD	Oregon Health and Science University
Principal Investigator:	David M. Cook, MD	Oregon Health and Science University

More Information

Additional Information:

Source for women's health information. This link exits the ClinicalTrials.gov site

Information for women about polycystic ovary syndrome from the American Academy of Family Physicians. This link exits the ClinicalTrials.gov site

Publications:

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.

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. Review. No abstract available.

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. Epub 2004 Jan 29.

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.

Essah PA, Nestler JE. Metabolic syndrome in women with polycystic ovary syndrome. Fertil Steril. 2006 Jul;86 Suppl 1:S18-9.

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.

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.

Responsible Party:	Oregon Health & Science University ( Kevin Yuen, MD )
Study ID Numbers:	IRB3711
Study First Received:	August 17, 2007
Last Updated:	July 21, 2008
ClinicalTrials.gov Identifier:	NCT00518635 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by Oregon Health and Science University:

Growth hormone
Insulin sensitivity
Polycystic ovary

Additional relevant MeSH terms:

Disease
Gonadal Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Endocrine System Diseases
Ovarian Diseases
Cysts
Hormones
Pharmacologic Actions

Insulin
Adnexal Diseases
Genital Diseases, Female
Neoplasms
Hypoglycemic Agents
Pathologic Processes
Syndrome
Polycystic Ovary Syndrome
Ovarian Cysts

ClinicalTrials.gov processed this record on February 08, 2010