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

Pennington Biomedical Research Center

Status and phase: Terminated; Phase 3

Conditions: Polycystic Ovary Syndrome

Treatments: Behavioral: Exercise Training; Drug: Metformin; Behavioral: Dietary Restriction

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01482286

R00HD060762 (U.S. NIH Grant/Contract)

PBRC11016

Details and patient eligibility

About

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.

Full 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.

Enrollment: 32 patients

Sex: Female

Ages: 20 to 40 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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32 participants in 4 patient groups

Metformin

Experimental group

Description:

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.

Treatment:

Drug: Metformin

Dietary Restriction

Experimental group

Description:

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.

Treatment:

Behavioral: Dietary Restriction

Exercise

Experimental group

Description:

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.

Treatment:

Behavioral: Exercise Training

Control

No Intervention group

Description:

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.