Myo-Inositol for Infertility in PCOS
Primary Purpose
Polycystic Ovary Syndrome
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Inositol supplement
Placebo supplement
Sponsored by
About this trial
This is an interventional supportive care trial for Polycystic Ovary Syndrome
Eligibility Criteria
Inclusion Criteria:
- Female patient age 18-36
- Desire for pregnancy
- Diagnosis of oligo- or anovulation secondary to polycystic ovary syndrome -All subjects must have ovulatory dysfunction and at least one of the remaining two criteria:hyperandrogenism or polycystic ovarian morphology on ultrasound
- At least one patent fallopian tube
- Normal uterine cavity
- Male partner with sperm concentration of at least 14 million/mL in at least one ejaculate.
Exclusion Criteria:
- Cause of anovulation other than PCOS such as uncontrolled thyroid dysfunction or hyperprolactinemia
- Presence of another major infertility factor
- Diabetes
- Contraindication to pregnancy
- Myo-inositol use < 3 months prior to study enrollment
- Concomitant metformin use. Previous use is allowed with last use at least 6 weeks prior to randomization.
Sites / Locations
- OUHSC Reproductive Medicine ClinicRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Placebo Comparator
Active Comparator
Arm Label
Control Arm
Inositol Arm
Arm Description
This group will receive placebo powder twice daily.
This group will receive myo-inositol (2,000mg) plus d-chiro-inositol (50mg) supplement powder twice daily.
Outcomes
Primary Outcome Measures
Clinical pregnancy
Clinical pregnancy will be defined as documentation of a viable intrauterine pregnancy as noted by visualization of fetal heart motion on ultrasonography.
Secondary Outcome Measures
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04407754
Brief Title
Myo-Inositol for Infertility in PCOS
Official Title
Myo-Inositol as an Adjuvant to Letrozole for Infertility in PolyCystic Ovary Syndrome (MALI-PCOS): a Randomized Pilot Trial
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 19, 2020 (Actual)
Primary Completion Date
September 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oklahoma
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
This will be a prospective, double-blind randomized clinical trial of letrozole and placebo versus letrozole and inositols for up to 5 treatment cycles of ovulation induction or until pregnancy is achieved. All participants and members of the research team will be blinded to the treatment arms. Placebo and inositol supplement will be packaged to appear the same, tested, and packaged by a commercial supply company. The inositols will be a 40:1 blend of myo-inositol and D-chiro inositol.
Detailed Description
At the screening visit, blood pressure and heart rate will be measured, weight and height obtained and body mass index calculated (kg/m2). If not already completed at their new patient visit, transvaginal ultrasound will be performed to assess uterine anatomy and obtain antral follicle count, TSH, prolactin, and testosterone will be drawn, and serum samples will be obtained and analyzed for metabolic parameters (fasting lipids, insulin, and complete metabolic panel). One additional tube of blood will be drawn to store for potential future analysis. Once enrolled, randomization will occur and subjects will start either inositols or placebo. 84 women will be stratified by BMI and randomized 1:1 into two treatment arms, A) "Control Arm" = twice daily placebo powder and B) "Inositol Arm" = twice daily myo-inositol (2,000mg) plus d-chiro-inositol (50mg) supplement powder.
Treatment with either placebo or inositol will begin upon randomization. Participants will complete a validated quality of life in PCOS questionnaire (PCOSQ) at this visit and again upon study completion (11). Treatment with letrozole will begin after the baseline visit, which will occur after spontaneous menses or withdrawal bleeding induced by progestin administration. Because of this timing, participants will undergo pretreatment with inositol or placebo for a variable amount of time up to 6 weeks, with an anticipated average of 2-3 weeks. Metabolic parameters will be repeated after approximately 6 (7-9) and approximately 12 (11-13) weeks of inositol or placebo, at whichever study visit is most proximal in time to this goal timeframe. Both groups will receive letrozole 5mg every day for 5 days on days 3-7 of their menstrual cycle and instructed on timing intercourse with anticipated ovulation dates. Blood will be drawn for a serum progesterone each cycle between cycle days 20-22 to confirm ovulation, and repeated 1 week later if the initial progesterone level is below the threshold to confirm ovulation. Once ovulation is confirmed, they patient will expect a period 7-10 days later. They will call with cycle day 1 of bleeding if it occurs to start their next cycle of treatment, up to 5 cycles. If no bleeding occurs within the expected timeframe, they will check a home pregnancy test and call with results. Patients will complete medication side effect questionnaires at the first blood draw for progesterone of each cycle. This will be reviewed same-day and in person with the research nurse coordinator. Each patient will complete up to 5 cycles. Dose of letrozole will be increased in subsequent cycles for non-response or late ovulatory response (ovulation later than the progesterone blood draw) up to 10mg of letrozole a day. For patients with a second progesterone level below the threshold to confirm ovulation (day 21 and day 28), the higher dose of letrozole will be initiated following the receipt of the second low progesterone result. For patients who do not ovulate on the maximum dose of letrozole, their study participation will be considered complete.
Data to be collected will include: demographic information and medical history [age, race/ethnicity, body mass index (BMI), antral follicle count, length of infertility, prior infertility treatment (yes or no), obstetrical history, medical history, surgical history, current medication and allergy lists], partner information [age, race/ethnicity, BMI, general medical health assessment, prior paternity history], transvaginal ultrasound results, and serum studies [TSH, prolactin, progesterone, hCG levels, androgen levels (total and free testosterone, SHBG), and metabolic factors (fasting lipid panel, fasting glucose, fasting insulin, glucose:insulin ratio, HOMA-IR index)]. Questionnaires to be completed include: PCOSQ validated questionnaire for PCOS-related quality of life, and a side effect questionnaire about known side effects of letrozole and inositols. In addition to the baseline transvaginal ultrasound, additional ultrasounds may be performed as indicated clinically (including for establishing clinical pregnancy). Pertinent demographic and clinical information on patients who are participating in the study will be entered into a study database REDCap secure software.
Using the reported clinical pregnancy rate for infertile PCOS patients treated with letrozole of 31.3% (12) as the control group proportion (0.31) with a goal of 10% effect size (and therefore treatment group proportion 0.41), an alpha of 0.05, and power of 0.8, our sample size is estimated (for a full clinical trial) at ~361 in each arm. In considering the previously observed drop-out rate of ~20% in a similar patient population (3), we estimate that for a full clinical trial, we would need 452 participants randomized in each arm. Based on previously published literature regarding estimation of pilot randomized trial sample sizes, we will target 9% of this sample size for our pilot study to suggest or identify a significant difference (13). In conclusion, our planned study size will be 42 participants in each study arm.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
168 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control Arm
Arm Type
Placebo Comparator
Arm Description
This group will receive placebo powder twice daily.
Arm Title
Inositol Arm
Arm Type
Active Comparator
Arm Description
This group will receive myo-inositol (2,000mg) plus d-chiro-inositol (50mg) supplement powder twice daily.
Intervention Type
Dietary Supplement
Intervention Name(s)
Inositol supplement
Intervention Description
Inositol supplements given to inositol arm
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo supplement
Intervention Description
Placebo supplement given to placebo arm
Primary Outcome Measure Information:
Title
Clinical pregnancy
Description
Clinical pregnancy will be defined as documentation of a viable intrauterine pregnancy as noted by visualization of fetal heart motion on ultrasonography.
Time Frame
Through study completion, an average of 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
36 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Female patient age 18-36
Desire for pregnancy
Diagnosis of oligo- or anovulation secondary to polycystic ovary syndrome -All subjects must have ovulatory dysfunction and at least one of the remaining two criteria:hyperandrogenism or polycystic ovarian morphology on ultrasound
At least one patent fallopian tube
Normal uterine cavity
Male partner with sperm concentration of at least 14 million/mL in at least one ejaculate.
Exclusion Criteria:
Cause of anovulation other than PCOS such as uncontrolled thyroid dysfunction or hyperprolactinemia
Presence of another major infertility factor
Diabetes
Contraindication to pregnancy
Myo-inositol use < 3 months prior to study enrollment
Concomitant metformin use. Previous use is allowed with last use at least 6 weeks prior to randomization.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Christy Zornes, MHR
Phone
4052718001
Ext
48137
Email
christy-zornes@ouhsc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kyra Woods, BA
Phone
4052718001
Ext
45750
Email
kyra-woods@ouhsc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Heather Burks, MD
Organizational Affiliation
OUHSC
Official's Role
Principal Investigator
Facility Information:
Facility Name
OUHSC Reproductive Medicine Clinic
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Heather Burks, MD
Phone
405-271-1616
Email
Heather-Burks@ouhsc.edu
12. IPD Sharing Statement
Learn more about this trial
Myo-Inositol for Infertility in PCOS
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