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Infertility, FemalePhase 3FIT-PLESENCT02432209

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

A Phase 3 study testing Caloric Restriction, Orlistat and Moderate physical activity in people with Infertility, Female, run by Yale University at 10 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 40 years, women only
Conditions the study is for
Infertility, Female
What is being tested?
Caloric Restriction, Orlistat and Moderate physical activity
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
379 participants
Where
10 sitesUnited States
Study dates
Aug 2015to May 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 40 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • Currently pregnant or successful pregnancies within 12 months of initiating participation. Clinical intrauterine miscarriages prior to initiating participation, within ASRM guidelines: subjects over 35 must wait six months, while subjects under 35 must wait 12 months. No exclusion for biochemical pregnancies.
  • 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.
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  • 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.
  • Couples with previous sterilization procedures (e.g. vasectomy, tubal ligation) whether or not it has been reversed.
  • Subjects with untreated poorly controlled hypertension defined as a systolic blood pressure ≥ 160 mm Hg or a diastolic ≥ 100 mm Hg obtained on two measures at least 60 minutes apart.
  • Subjects who have undergone a bariatric surgery procedure in the past or are in a period of acute weight loss (defined as a weight loss of greater than 5 kgs in the last 6 months).
  • Known moderate or severe endometriosis.
  • Anovulation or oligo-ovulation including hypothalamic amenorrhea, polycystic ovary syndrome, etc.
  • Donated semen.
  • Couples in which either partner is legally married to someone else.
  • Medical conditions that are contraindications to pregnancy.
  • Presence of severe, untreated psychiatric illness (major depression, substance abuse, eating disorder, etc.) that would, in the opinion of the site investigator, interfere with the patient's ability to successfully complete the study.
  • Any additional medical conditions that would be a contraindication to orlistat. (This includes patients with chronic malabsorption syndrome or cholestasis or known hypersensitivity to any of the drugs used in this study.)
  • Any contraindication to study requirements including diet recommendations and activity requirements.
  • Currently participating in a lifestyle intervention program (such as Weight Watchers, Atkins Diet, Curves) or lost more than 5% body weight within the last 6 months.
  • History of Gout.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United States10 sites
  • Augusta University

    Augusta, Georgia, 30912

  • University of North Carolina

    Chapel Hill, North Carolina, 27599

  • Atrium Health Carolinas Healthcare System

    Charlotte, North Carolina, 28204

  • Pennsylvania State University

    Hershey, Pennsylvania, 17033

  • University of Oklahoma

    Oklahoma City, Oklahoma, 73104

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • University of Rochester

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84132

  • University of California San Francisco

    San Francisco, California, 94115

  • Wayne State University

    Southfield, Michigan, 48034

Other trials in United States

About this study

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).

Read the detailed description

Study Objective An intensive lifestyle modification intervention (which includes caloric restriction, use of an over-the-counter weight loss medication, and moderate physical activity with tracking) designed to promote a weight loss of approximately 7% of initial body weight is more likely to achieve a good perinatal outcome (i.e. a healthy term normal weight infant) than a recommendation to standard lifestyle modification with moderate physical activity with tracking (based on publically available activity recommendations) in obese women with unexplained infertility.

Patient Population The population will consist of 380 obese women with unexplained infertility, age 18-40 years old. Subjects must have normal ovulatory function and normal ovarian reserve. Additionally, the couple will have no other major infertility factor: the subject will have at least one patent fallopian tube and a normal uterine cavity, and a partner total motile sperm count of at least 5 million in at least one ejaculate.

Study Design This will be 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).

Treatment 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. 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. Participants in both groups will receive activity tracking devices (Fitbit Wireless Activity Tracker) and wireless scales (Fitbit Aria Wireless Activity Scale) to promote adherence to the inventions and to allow monitoring for compliance by study personnel. The pretreatment intervention will last 16 weeks. Both groups will aim for activity levels of 10,000 steps/day, with a recommendation to increase steps from baseline by 500 steps/per week. The investigators will monitor subjects monthly during this preconception intervention. After 16 weeks of lifestyle modification, all subjects randomized will receive a standardized empiric infertility treatment, regardless of adherence or success in achieving treatment goals. This treatment will consist of ovarian stimulation with CC followed by ultrasound follicular monitoring, hCG trigger of ovulation, and a single partner intrauterine insemination (IUI) per treatment cycle for up to three treatment cycles. The goal for both treatment groups will be to maintain levels of physical activity and weight achieved during the pretreatment phase during the empiric infertility treatment phase. Subjects who conceive will be followed throughout pregnancy with the wireless activity monitor and wireless scale. Additionally there will be three brief onsite visits during pregnancy (per trimester at 16, 24, and 32 weeks) for onsite determination of weight, glycemic, and blood pressure changes and collection of biospecimens. All pregnancy outcomes will be tracked. Subjects who deliver will be encouraged to donate placenta and cord blood to the study repository and then to enroll in our Pregnancy Registry for continued infant follow-up. The investigators will also expand the number and variety of specimens that are collected for the repository from both partners including urine and serum, semen, saliva, placenta and cord blood.

Being tested
Caloric Restriction, Orlistat, Moderate physical activity
Medical subject headings
Infertility, Female

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Caloric RestrictionOther

    Also called Nutrisystem

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

  • OrlistatDrug

    Also called Alli

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

  • Moderate physical activityOther

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

Study groups in NCT02432209
Study groupRoleWhat they receive
Intensive Lifestyle Mod. InterventionActive comparatorThe 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.
Receives: Other: Caloric Restriction; Drug: Orlistat; Other: Moderate physical activity
Standard Lifestyle InterventionPlacebo comparatorWomen 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.
Receives: Other: Moderate physical activity

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: At time of birth, approximately 17 months into the study

Secondary outcomes (6)
  1. Live Birth Rate

    All the live birth for the study

    Measured: At time of birth, approximately 17 months into the study

  2. Time to Pregnancy in Days

    Days from randomization to the first known date of conception

    Measured: 0-8 months

  3. Pregnancy Loss Rate

    Pregnancy loss (conception without a live birth) among those who achieved pregnancy

    Measured: After conception, 0-13 months into the study

  4. Multiple Pregnancy Rate

    Determined by number of multiple pregnancies / number of pregnancies

    Measured: After conception, 1-13 months into the study

  5. Birth Weight in Grams

    Birth weight (grams) for infant delivered

    Measured: at time of birth, approximately 17 months into the study

  6. Mode of Delivery-Cesarean Section

    Babies by Cesarean Section/Number of participants who delivered baby

    Measured: At time of birth, approximately 17 months into the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 May 2015 (estimated)
  2. Study startAug 2015
  3. Primary completion30 Nov 2019
  4. Study completionMay 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
379 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02432209
Sponsor's protocol ID
FIT-Plese
Acronym
FIT-PLESE
Status last verified
Feb 2022
First submitted
16 Mar 2015
Last updated
3 Feb 2022
Data monitoring committee
Yes
Individual data sharing
Yes: IPD will be shared with other researchers through the NICHD DASH system. It will be available 6 months after publication of the primary results.

Publications

  • 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.

    PubMed 37719091
  • 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.

    PubMed 35041662

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Caloric Restriction, Orlistat and Moderate physical activity in people with Infertility, Female, run by Yale University at 10 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Mar 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of Good Birth Outcomes (time frame: At time of birth, approximately 17 months into the study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02432209, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2022.

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