Low Dose Growth Hormone in Obese PCOS Women

Oregon Health & Science University (OHSU)

Status

Withdrawn

Conditions

Polycystic Ovary Syndrome

Treatments

Drug: Nutropin

Study type

Interventional

Funder types

Other

Identifiers

NCT00518635

IRB3711

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 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.

Full description

The study will be a double-blinded cross-over study. Thirty subjects will be screened for eligibility initially, and the first 12 eligible subjects will be enrolled. Six subjects will be randomized to receive the low GH dose (0.1 mg/day) treatment and 6 subjects to receive Placebo treatment for 12 weeks, exchanging their treatment for a further 12 weeks after a 4-week washout period. The study drugs will be stored at the Oregon Health and Science University (OHSU) Research Pharmacy and following randomization, the subjects will be taught by our Endocrine Nurses to self-administer the subcutaneous GH and Placebo injections using Nutropin/Placebo vials and insulin syringes into the abdomen at 2200h. Randomization for treatment assignment will be performed by an investigator not directly involved in the patients' recruitment, treatment and follow-up care. The randomization process will be performed by computerized pre-assigned random codes by blocks, stratified by age and examined for possible differences in body mass index. During their in-patient stay at the Oregon Clinical and Translational Research Institute (OCTRI) at OHSU, subjects will only be allowed to eat the food provided to them by the OCTRI.

Initial Screening Assessment (outpatient)

The following assessments will be performed:

Written informed consent
Demographics (demographic information including the subject's birth date, and race)
Physical exam and medical history
Previous/significant medical history
Concomitant medication review
Vital signs, e.g., pulse and blood pressure measurements
Height and weight
Laboratory findings, e.g. CBC, electrolytes, and fasting glucose levels
- Visit 1, Baseline Assessment for the First Treatment Phase (in-patient)

The following is a description of the assessments that will be performed after consent is obtained:

Physical exam and medical history
Vital signs, e.g., pulse and blood pressure measurements
Height and weight
Waist circumference measurement
Concomitant medication review
Urine pregnancy test
Fasting blood assessments, e.g., hemoglobin, glucose, insulin, C-peptide, serum total and free IGF-I, IGFBP-3, C-reactive protein, non-esterified fatty acids (NEFAs), testosterone, albumin, sex hormone binding globulin and androstenedione
A 3-hour one-step hyperinsulinemic euglycemic clamp
MRS and DEXA scans
Cortisol clearance rate assessments
Fat biopsy
Randomization to GH or Placebo
Teach GH or Placebo self-administration
- Visit 2, Final Assessment for the First Treatment Phase (Week 12 +/- 1 week) (outpatient)

The following is a description of the assessments that will be performed at the end of the first treatment phase with either GH or Placebo. Subjects will also be monitored for safety with the collection of the following:

Physical exam and medical history
Vital signs, e.g. pulse and blood pressure measurements
Height and weight
Waist circumference measurement
Concomitant medication review
Adverse event recording
Urine pregnancy test
Fasting blood assessments, e.g. hemoglobin, glucose, insulin, C-peptide, serum total and free IGF-I, IGFBP-3, C-reactive protein, adiponectin, ghrelin, non-esterified fatty acids (NEFAs), testosterone, albumin, sex hormone binding globulin and androstenedione
A 3-hour one-step hyperinsulinemic euglycemic clamp
MRS and DEXA scans
Cortisol clearance rate assessments
Fat biopsy

Washout Period and Crossover After the first treatment phase with GH or Placebo, the subjects will have a 4-week washout period and the treatment will be crossed over for another 12-week treatment phase with either GH or Placebo. During this time, the subjects will be advised to maintain a stable diet and weight.

Visit 3, Baseline Assessment for the Second Treatment Phase (Week 16 +/- 1 week) (as outpatient)

The following is a description of the assessments that will be performed:

Physical exam and medical history
Vital signs, e.g., pulse and blood pressure measurements
Height and weight
Waist circumference measurement
Concomitant medication review
Adverse event recording
Urine pregnancy test
Fasting blood assessments, e.g. hemoglobin, glucose, insulin, C-peptide, serum total and free IGF-I, IGFBP-3, C-reactive protein, adiponectin, ghrelin, non-esterified fatty acids (NEFAs), testosterone, albumin, sex hormone binding globulin and androstenedione
Treatment exchanged to Placebo or GH
- Visit 4, Final Assessment for the Second Treatment Phase (Week 28 +/- 1 week) (as inpatient)

The following is a description of the assessments that will be performed at the end of the second treatment phase with either GH or Placebo. Subjects will also be monitored for safety with the collection of the following:

Physical exam and medical history
Vital signs, e.g. pulse and blood pressure measurements
Height and weight
Waist circumference measurement
Concomitant medication review
Adverse event recording
Urine pregnancy test
Fasting blood assessments, e.g., hemoglobin, glucose, insulin, C-peptide, serum total and free IGF-I, IGFBP-3, C-reactive protein, adiponectin, ghrelin, non-esterified fatty acids (NEFAs), testosterone, albumin, sex hormone binding globulin and androstenedione
A 3-hour one-step hyperinsulinemic euglycemic clamp
MRS and DEXA scans
Cortisol clearance rate assessments
Fat biopsy
- Because of the potentially long duration of Visits 1, 2 and 4, the studies can either be divided into two separate admissions upon prior arrangement or can be done all at once with one admission, depending on the subject's wishes and schedule.

Sex

Female

Ages

21 to 45 years old

Volunteers

No Healthy Volunteers

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