Improving Reproductive Fitness Through Pretreatment With Lifestyle Modification in Obese Women With Unexplained Infertility

NCT02432209 | Completed Phase 3 Results DMC

• 1 other identifier: FIT-Plese
• Study Type: interventional
• Target: 379
• Locations: 1 country
• Sites: 10

Brief Summary

A two-arm, multicenter, prospective, randomized clinical trial of a lifestyle modification program with tracked increased physical activity and weight loss (intensive) compared to recommendations to tracking of increased physical activity alone with weight maintenance (standard) in women with obesity and unexplained infertility. This 16 week period of lifestyle modification will be followed by an open label empiric infertility treatment regimen consisting of three cycles of ovarian stimulation with oral medication (clomiphene citrate (CC)), triggering of ovulation with human chorionic gonadotropin (hCG) and intrauterine insemination (IUI).

Conditions

Infertility, Female

Outcome Measures

Primary Outcomes (1)

• Rate of Good Birth Outcomes

  Defined as a live birth of an infant born at ≥ 37 weeks, with a birth weight between 2500 and 4000g and without a major congenital anomaly

  At time of birth, approximately 17 months into the study

Secondary Outcomes (6)

• Live Birth Rate

  At time of birth, approximately 17 months into the study

• Time to Pregnancy in Days

  0-8 months

• Pregnancy Loss Rate

  After conception, 0-13 months into the study

• Multiple Pregnancy Rate

  After conception, 1-13 months into the study

• Birth Weight in Grams

  at time of birth, approximately 17 months into the study

Study Arms (2)

Intensive Lifestyle Mod. Intervention

ACTIVE COMPARATOR

The intensive lifestyle modification intervention will consist of caloric restriction (consumption of approximately 1200-1500 kcal/d), use of an over-the-counter weight loss medication (Alli, which is brand name Orlistat, a gastric lipase inhibitor that limits gut fat absorption), and moderate physical activity (goal of reaching 10,000 steps a day). The pretreatment intervention will last 16 weeks and is designed to promote a weight loss of approximately 7% of total body weight.

Other: Caloric Restriction; Drug: Orlistat; Other: Moderate physical activity

Standard Lifestyle Intervention

PLACEBO COMPARATOR

Women in the standard lifestyle intervention (standard) will receive publicly available written materials that promote engagement in moderate physical activity with target of 10,000 steps a day. Detailed instruction of physical activity will not be provided.

Other: Moderate physical activity

Interventions

Caloric Restriction OTHER

Subjects on Active comparator will have Caloric Restriction to a 1200-1500 kcal/day diet through use of Nutrisystem Meal Plan.

Also known as: Nutrisystem

Intensive Lifestyle Mod. Intervention

Orlistat DRUG

Subjects on Active comparator will use an over-the-counter weight loss medication, Orlistat, a gastric lipase inhibitor that limits gut fat absorption.

Also known as: Alli

Intensive Lifestyle Mod. Intervention

Moderate physical activity OTHER

All subjects in both arms will be encouraged to engage in moderate physical activity with target of 10,000 steps a day.

Intensive Lifestyle Mod. Intervention; Standard Lifestyle Intervention

Eligibility Criteria

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

You may qualify if:

• Women ≥18 to ≤ 40 years of age, with one or more years infertility history, desirous of conceiving, regularly ovulating (defined as 9 or more menses per year), at initiation of participation.
• BMI ≥ 30 kg/m2.
• Normal uterine cavity and at least one open fallopian tube confirmed by hysterosalpingography (HSG), sonohysterography (SHG), or laparoscopy/hysteroscopy in the last three years preceding enrollment into the study. An uncomplicated intrauterine non-IVF pregnancy and uncomplicated delivery and postpartum course resulting in live birth within the last three years will also serve as sufficient evidence of a patent tube and normal uterine cavity as long as the subject did not have, during the pregnancy or subsequently, risk factors for Asherman's syndrome or serious pelvic infection or other disorder leading to an increased suspicion for intrauterine abnormality or tubal occlusion.
• Evidence of ovarian function/reserve as assessed by menstrual cycle day 3 (+/-2 days) FSH ≤10 IU/L with estradiol ≤ 70 pg/mL OR AMH ≥ 1 ng/mL within one year prior to study initiation.
• Normal or corrected thyroid function within one year of study initiation.
• Normal or corrected prolactin level within one year of study initiation.
• In general good health, not taking any medications which could interfere with the study (e.g., FSH, insulin sensitizers).
• Ability to have inseminations following hCG administration.
• Male partner with total motile sperm in the ejaculate of at least 5 million sperm, within one year of study initiation.
• Able to comply with intercourse instructions and collection of semen for insemination.

You may not qualify if:

• Undiagnosed abnormal uterine bleeding.
• Suspicious ovarian mass.
• Subjects on oral contraceptives, depo-progestins, or hormonal implants (including Implanon). A two month washout period will be required prior to screening for patients on these agents. Longer washouts may be necessary for certain depot contraceptive methods or implants, especially when the implants are still in place. A one-month washout will be required for patients taking oral cyclic progestins.
• Known 21-hydroxylase deficiency or other enzyme defect causing congenital adrenal hyperplasia.
• Type I or Type II diabetes mellitus, or if receiving antidiabetic medications.
• Known significant anemia (Hemoglobin \<10 g/dL).
• History of deep venous thrombosis, pulmonary embolus, or cerebrovascular event.
• Known heart disease (New York Heart Association Class II or higher).
• Known Liver disease (defined as AST or ALT\>2 times normal, or total bilirubin \>2.5 mg/dL).
• Known Renal disease (defined as BUN \>30 mg/dL or serum creatinine \> 1.4 mg/dL).
• History of, or suspected cervical carcinoma, endometrial carcinoma or breast carcinoma.
• History of alcohol abuse (defined as \>14 drinks/week) or binge drinking of ≥ 6 drinks at one time).
• Known Cushing's disease.
• Known or suspected adrenal or ovarian androgen secreting tumors.
• Allergy or contraindication to the treatment medications: CC or hCG.

Sponsors & Collaborators

• Yale University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• Penn State University: collaborator
• Augusta University: collaborator
• University of California, San Francisco: collaborator
• University of North Carolina: collaborator
• University of Oklahoma: collaborator
• University of Pennsylvania: collaborator

Study Sites (10)

University of California San Francisco

San Francisco, California, 94115, United States

Location

Augusta University

Augusta, Georgia, 30912, United States

Location

Wayne State University

Southfield, Michigan, 48034, United States

Location

University of Rochester

Rochester, New York, 14642, United States

Location

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Atrium Health Carolinas Healthcare System

Charlotte, North Carolina, 28204, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Pennsylvania State University

Hershey, Pennsylvania, 17033, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Related Publications (2)

• Vitek WS, Sun F, Cardozo E, Hoeger KM, Hansen KR, Santoro N, Zhang H, Legro RS. Moderate and increased physical activity is not detrimental to live birth rates among women with unexplained infertility and obesity. F S Rep. 2023 Jun 24;4(3):308-312. doi: 10.1016/j.xfre.2023.06.004. eCollection 2023 Sep.

  PMID: 37719091 DERIVED

• Legro RS, Hansen KR, Diamond MP, Steiner AZ, Coutifaris C, Cedars MI, Hoeger KM, Usadi R, Johnstone EB, Haisenleder DJ, Wild RA, Barnhart KT, Mersereau J, Trussell JC, Krawetz SA, Kris-Etherton PM, Sarwer DB, Santoro N, Eisenberg E, Huang H, Zhang H; Reproductive Medicine Network. Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial. PLoS Med. 2022 Jan 18;19(1):e1003883. doi: 10.1371/journal.pmed.1003883. eCollection 2022 Jan.

  PMID: 35041662 DERIVED

MeSH Terms

Conditions

Infertility, Female

Interventions

Caloric Restriction; Orlistat

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Lactones; Organic Chemicals

Results Point of Contact

• Title: Fangbai Sun
• Organization: Yale School of Public Health

fangbai.sun@yale.edu

2037855185

Study Officials

• Nanette Santoro, MD

  University of Colorado, Denver

  STUDY CHAIR

• Heping Zhang, PhD

  Yale University

  STUDY DIRECTOR

• Richard Legro, MD

  Penn State University

  PRINCIPAL INVESTIGATOR

• Michael Diamond, MD

  Augusta University

  STUDY DIRECTOR

• Marcelle Cedars, MD

  University of California, San Francisco

  STUDY DIRECTOR

• Anne Steiner, MD MPH

  Univeristy of North Carolina

  STUDY DIRECTOR

• Karl Hansen, MD PhD

  University of Oklahoma

  STUDY DIRECTOR

• Christos Coutifaris, MD PhD

  University of Pennsylvania

  STUDY DIRECTOR

• Esther Eisenberg, MD MPH

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

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 16, 2015
• First Posted: May 4, 2015
• Study Start: August 1, 2015
• Primary Completion: November 30, 2019
• Study Completion: May 1, 2020
• Last Updated: February 3, 2022
• Results First Posted: March 15, 2021

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will share

Locations

US (10)