Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS (PULSE)

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Pennington Biomedical Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Leanne Redman, Pennington Biomedical Research Center
ClinicalTrials.gov Identifier:
NCT01482286
First received: November 28, 2011
Last updated: November 27, 2013
Last verified: November 2013

November 28, 2011
November 27, 2013
May 2012
August 2014   (final data collection date for primary outcome measure)
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)
LH pulsatility [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]
Change in LH pulsatility measured over 12h (7pm - 7am)
Complete list of historical versions of study NCT01482286 on ClinicalTrials.gov Archive Site
Insulin sensitivity [ Time Frame: Baseline and week 24 ] [ Designated as safety issue: No ]
Change in insulin sensitivity measured by the euglycemic hyperinsulinemic clamp
Same as current
Not Provided
Not Provided
 
Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Polycystic Ovary Syndrome
  • 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 Name: metformin hydrochloride tablets
  • Behavioral: 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
  • 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.
    Intervention: Drug: Metformin
  • 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.
    Intervention: Behavioral: Dietary Restriction
  • 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.
    Intervention: Behavioral: Exercise Training
  • 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.
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
52
December 2014
August 2014   (final data collection date for primary outcome measure)

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
Female
20 Years to 40 Years
No
Contact: Erin Lejeune, B.S. 2257632709 erin.lejeune@pbrc.edu
United States
 
NCT01482286
PBRC11016 PULSE, R00HD060762
Yes
Leanne Redman, Pennington Biomedical Research Center
Pennington Biomedical Research Center
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Leanne M Redman, PhD Pennington Biomedical Research Center
Pennington Biomedical Research Center
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP