Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS

NCT01482286 | Terminated Phase 3 Results DMC

• 2 other identifiers: PBRC11016R00HD060762
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycystic Ovary Syndrome

Keywords

Exercise; Diet; Insulin resistance; Weight

Outcome Measures

Primary Outcomes (1)

• Luteinizing Hormone (LH) Pulse Frequency

  Change in Luteinizing Hormone (LH) Pulse Frequency measured over a 12-hour period (7:00 PM - 7:00 AM). The Mean and Standard Deviation (SD) are the number of pulses recorded on the 12-hour period (7:00 PM - 7:00 AM) and presented as the change from baseline to week 24. Only participants who completed the PULSE trial are included in present outcome measure as the primary outcome was established as change from pre-to-post-intervention LF pulse frequency.

  Baseline and Week 24

Secondary Outcomes (1)

• Insulin Sensitivity Expressed as Glucose Disposal Rate (GDR)

  Baseline and Week 24

Study Arms (4)

Metformin

EXPERIMENTAL

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.

Drug: Metformin

Dietary Restriction

EXPERIMENTAL

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.

Behavioral: Dietary Restriction

Exercise

EXPERIMENTAL

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.

Behavioral: Exercise Training

Control

NO INTERVENTION

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.

Interventions

Metformin 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.

Also known as: metformin hydrochloride tablets

Metformin

Dietary Restriction 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.

Also known as: 25% DR, Calorie restriction

Dietary Restriction

Exercise Training 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.

Also known as: Aerobic and resistance training

Exercise

Eligibility Criteria

• Age: 20 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808, United States

Location

Related Publications (2)

• 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.

  PMID: 30377436 DERIVED

• 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.

  PMID: 28323951 DERIVED

Related Links

• Press Release: New Study at Pennington Biomedical Research Center Designed to Identify Factors Affecting Infertility in Women
• Study information and how to participate

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Motor Activity; Insulin Resistance; Body Weight

Interventions

Metformin; Diet Therapy; Caloric Restriction; Exercise; Resistance Training

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Behavior; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Exercise Therapy; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Physical Therapy Modalities; Physical Conditioning, Human

Results Point of Contact

• Title: Dr. Joshua R. Sparks
• Organization: Pennington Biomedical Research Center

joshua.sparks@pbrc.edu

2257632928

Study Officials

• Leanne M Redman, PhD

  Pennington Biomedical Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 28, 2011
• First Posted: November 30, 2011
• Study Start: May 1, 2012
• Primary Completion: April 1, 2016
• Study Completion: December 1, 2016
• Last Updated: March 15, 2022
• Results First Posted: March 2, 2022

Record last verified: 2022-03

Locations

US (1)