Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS

NCT ID: NCT01482286

Last Updated: 2022-03-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-05-31
• Study Completion Date: 2016-12-31

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.

Conditions

Polycystic Ovary Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Dietary Restriction

Intervention Type: BEHAVIORAL

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.

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.

Group Type: EXPERIMENTAL

Exercise Training

Intervention Type: BEHAVIORAL

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.

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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 Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Other Intervention Names

metformin hydrochloride tablets; 25% DR; Calorie restriction; Aerobic and resistance training

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).

• 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

• 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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Pennington Biomedical Research Center

OTHER

Sponsor Role: lead

Responsible Party

Leanne Redman

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Leanne M Redman, PhD

Role: PRINCIPAL_INVESTIGATOR

Pennington Biomedical Research Center

Locations

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Countries

United States

References

Broskey NT, Tam CS, Sutton EF, Altazan AD, Burton JH, Ravussin E, Redman LM. Metabolic inflexibility in women with PCOS is similar to women with type 2 diabetes. Nutr Metab (Lond). 2018 Oct 20;15:75. doi: 10.1186/s12986-018-0312-9. eCollection 2018.

Reference Type: DERIVED

PMID: 30377436 (View on PubMed)

Broskey NT, Klempel MC, Gilmore LA, Sutton EF, Altazan AD, Burton JH, Ravussin E, Redman LM. Assessing Energy Requirements in Women With Polycystic Ovary Syndrome: A Comparison Against Doubly Labeled Water. J Clin Endocrinol Metab. 2017 Jun 1;102(6):1951-1959. doi: 10.1210/jc.2017-00459.

Reference Type: DERIVED

PMID: 28323951 (View on PubMed)

Related Links

http://www.pbrc.edu/news/?ArticleID=134

Press Release: New Study at Pennington Biomedical Research Center Designed to Identify Factors Affecting Infertility in Women

http://www.pbrc.edu/clinical-trials/current-studies/?studyid=124

Study information and how to participate

Other Identifiers

R00HD060762

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PBRC11016

Identifier Type: -

Identifier Source: org_study_id