Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS | RxWiki

Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS

Overview[ - collapse ][ - ]

Purpose	Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women of reproductive age and despite decades of research the etiology the disorder is not known. The characteristic hyperandrogenism and anovulation is associated with abnormal neuroendocrine function and insulin resistance. Obesity is a common correlated phenotype of Polycystic ovary syndrome and weight gain worsens the reproductive and metabolic complications. Currently there is no evidence-based treatment plan for infertility in Polycystic ovary syndrome; yet weight loss by dietary restriction and regular exercise are strongly advocated. Weight loss and increased insulin sensitivity appear to drive improvements in reproductive outcomes in women with Polycystic ovary syndrome; however, the mechanism connecting these changes with the reproductive axis is not fully understood.
Condition	Polycystic Ovary Syndrome
Intervention	Drug: Metformin Behavioral: Dietary Restriction Behavioral: Exercise Training
Phase	Phase 3
Sponsor	Pennington Biomedical Research Center
Responsible Party	Pennington Biomedical Research Center
ClinicalTrials.gov Identifier	NCT01482286
First Received	November 28, 2011
Last Updated	November 27, 2013
Last verified	November 2013

Tracking Information[ + expand ][ + ]

First Received Date	November 28, 2011
Last Updated Date	November 27, 2013
Start Date	May 2012
Estimated Primary Completion Date	December 2014
Current Primary Outcome Measures	Pulsatility profile of Luteinizing Hormone (LH) [Time Frame: Baseline, Week 24] [Designated as safety issue: No]Change in LH pulsatility measured over 12h (7pm - 7am)
Current Secondary Outcome Measures	Insulin sensitivity [Time Frame: Baseline and week 24] [Designated as safety issue: No]Change in insulin sensitivity measured by the euglycemic hyperinsulinemic clamp

Descriptive Information[ + expand ][ + ]

Brief Title	Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Official Title	Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Brief Summary	Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women of reproductive age and despite decades of research the etiology the disorder is not known. The characteristic hyperandrogenism and anovulation is associated with abnormal neuroendocrine function and insulin resistance. Obesity is a common correlated phenotype of Polycystic ovary syndrome and weight gain worsens the reproductive and metabolic complications. Currently there is no evidence-based treatment plan for infertility in Polycystic ovary syndrome; yet weight loss by dietary restriction and regular exercise are strongly advocated. Weight loss and increased insulin sensitivity appear to drive improvements in reproductive outcomes in women with Polycystic ovary syndrome; however, the mechanism connecting these changes with the reproductive axis is not fully understood.
Detailed Description	The goal of this study is to determine (using dietary restriction, exercise training, metformin or no treatment), the effects of weight loss and/or improved insulin sensitivity on reproductive function (neuroendocrine and ovarian) in obese women with Polycystic ovary syndrome.
Study Type	Interventional
Study Phase	Phase 3
Study Design	Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Polycystic Ovary Syndrome
Intervention	Drug: Metformin Subjects randomized to the metformin treatment group will receive 1000 mg extended release metformin hydrochloride tablets (Bristol Myers Squibb) twice per day with food approximately 8 hours apart. Other Names: metformin hydrochloride tabletsBehavioral: Dietary Restriction Subjects randomized to the dietary restriction group will reduce their energy intake by 25% of their weight maintenance energy intake determined at baseline. Total energy expenditure as measured by a 14-day doubly labeled water (DLW) study will be used to determine the baseline energy intake of each subject. There will be no gradual ramping of dietary restriction. The 25% energy reduction goal will apply from the first day of the intervention for a period of 24 weeks. Subjects will be asked to not modify their normal level of physical activity. Other Names: 25% DR Calorie restriction Dietary restriction Behavioral: Exercise Training For the aerobic training component, subjects are required to meet a weekly energy expenditure target of 10 kcal per kg of body weight per week (KKW). The resistance training program will be performed 2 days a week. The resistance program includes 9 exercises. The 9 primary exercises are seated chest press, seated row, shoulder press, lat pull down, double leg press, leg extension, leg curl, back extension and abdominal crunch. Other Names: Exercise training Aerobic and resistance training
Study Arm (s)	Experimental: Metformin Subjects randomized to the metformin treatment group will receive 1000 mg extended release metformin hydrochloride tablets (Bristol Myers Squibb) twice per day with food approximately 8 hours apart. Experimental: Dietary Restriction Subjects randomized to the dietary restriction group (DR) will reduce their energy intake by 25% from their weight maintenance energy intake determined at baseline by doubly labeled water.There will be no gradual ramping of dietary restriction. The 25% energy reduction goal will apply from the first day of the intervention for a period of 24 weeks. Subjects will be asked to not modify their normal level of physical activity. Experimental: Exercise Subjects randomized to the exercise training group will complete a structured program of aerobic training 3 to 4 times per week and resistance exercises 2 times per week. No Intervention: Control Subjects randomized to the no treatment control group will be asked to continue, as normal their usual dietary and exercise regimen. Subjects will be asked to not begin diet or exercise regimens through the 24-week study or to begin medical treatment for PCOS.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	52
Estimated Completion Date	December 2014
Estimated Primary Completion Date	August 2014
Eligibility Criteria	Inclusion Criteria: - 20 - 40 years, inclusive - Body mass index ≥ 25 kg/m2 - History of irregular menstrual cycles (fewer than 6 cycles in the past year) - Clinical and/or biochemical androgen excess (Free androgen index>3.85 and/or hirsuitism rating ≥8) - Anovulatory menstrual cycles (determined during screening) Exclusion Criteria: - Ovulatory menstrual cycles (determined during screening by luteal phase serum progesterone >3ng/mL) - History or clinical appearance of cardiovascular disease, diabetes (Type 1 or Type 2) and any other significant reproductive, metabolic, hematologic, pulmonary, gastrointestinal, neurologic, immune, hepatic, renal, urologic disorders, or cancer. - Hemoglobin, hematocrit, red blood cell count, or iron level below the lower limit of normal at the screening visit confirmed by a test repeated within two weeks - Regular use of medications for weight control, glucose intolerance, thyroid disease - Use of hormonal contraception containing medroxyprogesterone acetate (A 3 month washout period will be permitted for oral, vaginal and transdermal contraceptives). Psychiatric and Behavioral Exclusion Criteria - Smoking - History of drug or alcohol abuse (up to 14 drinks a week are allowed) within the past two years - History or presence of an eating disorder as determined by Interview for Diagnosis of Eating Disorders (IDED-IV) - Beck Depression Index (BDI) score of ≥15 at screening or baseline Other Exclusion Criteria - Individuals who have lost more than 5kg (11lbs) in the past 6 months - Individuals who are pregnant or breast-feeding or whom become pregnant during the study - Individuals engaged in a regular program of physical fitness involving some heavy physical activity (e.g., jogging or riding fast on a bicycle for 30 minutes or more) at least five times per week over the past year - Individuals who have metallic objects in their body - Individuals who donated blood within 30 days prior to the date of randomization - Individuals unwilling to be assigned at random to either one of the intervention groups - Unwilling or unable to adhere to the rigors of the data collection (determined by food and activities diaries at screening, see below) and clinical evaluation schedule over the entire 24 week intervention period - Individuals who plan to move out of the area within the next 12 months or plan to be out of the study area for more than 4 weeks in the next 12 months - Individuals who reside too far from Pennington
Gender	Female
Ages	20 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Erin Lejeune, B.S. 2257632709 erin.lejeune@pbrc.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01482286
Other Study ID Numbers	PBRC11016 PULSE
Has Data Monitoring Committee	Yes
Information Provided By	Pennington Biomedical Research Center
Study Sponsor	Pennington Biomedical Research Center
Collaborators	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators	Principal Investigator: Leanne M Redman, PhD Pennington Biomedical Research Center
Verification Date	November 2013

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