search
Back to results

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

Primary Purpose

Polycystic Ovary Syndrome

Status
Terminated
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Metformin
Dietary Restriction
Exercise Training
Sponsored by
Pennington Biomedical Research Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Polycystic Ovary Syndrome focused on measuring Exercise, Diet, Insulin resistance, Weight

Eligibility Criteria

20 Years - 40 Years (Adult)FemaleDoes not accept 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

Sites / Locations

  • Pennington Biomedical Research Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

No Intervention

Arm Label

Metformin

Dietary Restriction

Exercise

Control

Arm 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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Insulin Sensitivity Expressed as Glucose Disposal Rate (GDR)
Change in insulin sensitivity measured by the euglycemic hyperinsulinemic clamp. Unit of measure established as glucose disposal rate (GDR) adjusted to account for kilograms of fat-free mass (FFM)+17.7 per minute to reflect the amount of exogenous glucose necessary to fully compensate for hyperinsulinemia and expressed as a function of metabolic body size. 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 Insulin Sensitivity expressed as Glucose Disposal Rate.

Full Information

First Posted
November 28, 2011
Last Updated
March 3, 2022
Sponsor
Pennington Biomedical Research Center
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
search

1. Study Identification

Unique Protocol Identification Number
NCT01482286
Brief Title
Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Acronym
PULSE
Official Title
Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Terminated
Why Stopped
Poor recruitment and enrollment.
Study Start Date
May 2012 (Actual)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Pennington Biomedical Research Center
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
Keywords
Exercise, Diet, Insulin resistance, Weight

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Metformin
Arm Type
Experimental
Arm 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.
Arm Title
Dietary Restriction
Arm Type
Experimental
Arm 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.
Arm Title
Exercise
Arm Type
Experimental
Arm 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.
Arm Title
Control
Arm Type
No Intervention
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
metformin hydrochloride tablets
Intervention 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.
Intervention Type
Behavioral
Intervention Name(s)
Dietary Restriction
Other Intervention Name(s)
25% DR, Calorie restriction
Intervention Description
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
Intervention Name(s)
Exercise Training
Other Intervention Name(s)
Aerobic and resistance training
Intervention Description
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.
Primary Outcome Measure Information:
Title
Luteinizing Hormone (LH) Pulse Frequency
Description
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.
Time Frame
Baseline and Week 24
Secondary Outcome Measure Information:
Title
Insulin Sensitivity Expressed as Glucose Disposal Rate (GDR)
Description
Change in insulin sensitivity measured by the euglycemic hyperinsulinemic clamp. Unit of measure established as glucose disposal rate (GDR) adjusted to account for kilograms of fat-free mass (FFM)+17.7 per minute to reflect the amount of exogenous glucose necessary to fully compensate for hyperinsulinemia and expressed as a function of metabolic body size. 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 Insulin Sensitivity expressed as Glucose Disposal Rate.
Time Frame
Baseline and Week 24

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Leanne M Redman, PhD
Organizational Affiliation
Pennington Biomedical Research Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Pennington Biomedical Research Center
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70808
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
30377436
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.
Results Reference
derived
PubMed Identifier
28323951
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.
Results Reference
derived
Links:
URL
http://www.pbrc.edu/news/?ArticleID=134
Description
Press Release: New Study at Pennington Biomedical Research Center Designed to Identify Factors Affecting Infertility in Women
URL
http://www.pbrc.edu/clinical-trials/current-studies/?studyid=124
Description
Study information and how to participate

Learn more about this trial

Effect of Weight and Insulin Sensitivity on Reproductive Function in PCOS

We'll reach out to this number within 24 hrs