Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04407754 |
| Other study ID # |
12103 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
December 19, 2020 |
| Est. completion date |
August 2024 |
Study information
| Verified date |
November 2023 |
| Source |
University of Oklahoma |
| Contact |
Christy Zornes, MHR |
| Phone |
4052718001 |
| Email |
christy-zornes[@]ouhsc.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
