Clinical trial NCT01482286: Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Official title: Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Polycystic Ovary Syndrome
Keywords: Exercise
Diet
Insulin resistance
Weight
Lead sponsor: Pennington Biomedical Research Center
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2011-11-30
Enrollment: 32
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Luteinizing Hormone (LH) Pulse Frequency
timeFrame: Baseline and Week 24
Secondary outcomes:
measure: Insulin Sensitivity Expressed as Glucose Disposal Rate (GDR)
timeFrame: Baseline and Week 24
Other outcomes:
Locations:
city: Baton Rouge
country: United States
facility: Pennington Biomedical Research Center
state: Louisiana
Study officials:
affiliation: Pennington Biomedical Research Center
name: Leanne M Redman, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.