Low Dose Growth Hormone in Obese PCOS Women
کلید واژه ها
خلاصه
شرح
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.
تاریخ
| آخرین تأیید شده: | 01/31/2013 |
| اولین ارسال: | 08/16/2007 |
| ثبت نام تخمینی ارسال شد: | 08/16/2007 |
| اولین ارسال: | 08/20/2007 |
| آخرین بروزرسانی ارسال شده: | 02/17/2013 |
| آخرین به روزرسانی ارسال شده: | 02/19/2013 |
| تاریخ شروع مطالعه واقعی: | 09/30/2010 |
| تاریخ تخمین اولیه اولیه: | 09/30/2011 |
| تاریخ برآورد مطالعه: | 09/30/2011 |
شرایط یا بیماری
مداخله / درمان
Drug: A
فاز
گروههای بازو
| بازو | مداخله / درمان |
|---|---|
| Experimental: A Growth hormone or Placebo 0.1 mg/day self-administrated once a day. | Drug: A Nutropin 0.1 mg/day self-administered once a day |
معیارهای صلاحیت
| سنین واجد شرایط تحصیل | 21 Years به 21 Years |
| جنسیت واجد شرایط مطالعه | Female |
| داوطلبان سالم را می پذیرد | آره |
| شاخص | 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 |
نتیجه
اقدامات اولیه
1. Changes in insulin sensitivity, and adipocyte IGF-I and insulin receptor signaling. [24 months]
اقدامات ثانویه
1. Changes in body composition, cortisol production rates, and muscle and liver intramyocellular content. [24 months]
