Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05050916 |
| Other study ID # |
10000476 |
| Secondary ID |
000476-E |
| Status |
Active, not recruiting |
| Phase |
Phase 1/Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
March 17, 2023 |
| Est. completion date |
November 30, 2024 |
Study information
| Verified date |
March 20, 2024 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Background:
About 1.5 million U.S. women of reproductive age are estimated to be infertile. Many more
have difficulty getting pregnant. Menstrual cycles are an indicator of a woman s general
health. Menstrual cycle changes may predict difficulties in getting pregnant. Researchers
want to see what role vitamin D may play in menstrual cycle health.
Objective:
To examine the effect of vitamin D supplementation on the hormones that come from the brain
and the ovary during a menstrual cycle.
Eligibility:
Women aged 19-40 who have spontaneous menstrual cycles (are not taking any hormones) less
than 50 days in length.
Design:
Participants will fill out a screening survey about their demographics and health history. It
will take 5-10 minutes to complete.
Participants will have 3 study visits. Participants who are deficient and move to Phase 2
will receive a 5000 IU dose of vitamin D supplements. Participants who are sufficient will
receive placebo. If they are vitamin D deficient, they will not get the placebo. They will
take the capsules by mouth, once per week, for 3 menstrual cycles (or about 90 days).
Participants will have physical exams. Their height, weight, body fat percentage, blood
pressure, and waist-hip ratio will be measured. They will give blood samples. They will have
self-administered vaginal and oral swabs.
Participants will keep a daily menstrual diary. They will do daily home ovulation testing.
They will collect urine at home. Some women may collect menstrual blood at home.
Participants will fill out an online survey. It will ask about their health, diet, and
physical activity; birth control use; pregnancy history; menstrual cycle; smoking and
drinking habits; education; and occupation. It will take 20-30 minutes to complete.
Participation will last for four menstrual cycles (about 4 months).
Description:
Study Description:
This Phase II randomized, dose-ranging clinical trial translates both animal studies and
human observational research into public health relevant research. We will investigate
vitamin D s influence on the hypothalamic-pituitary-ovarian axis by careful evaluation of
hormonal and ovulatory menstrual cycle changes that occur with vitamin D supplementation.
Vitamin D supplementation may be a low-cost intervention that improves menstrual cycle
function and
fertility.
After recruitment, there will be two phases to this study: Phase 1 will follow all women for
at least one menstrual cycle prior to supplementation, the pre-supplementation cycle . During
Phase 1, blood will be drawn and assayed for 25-hydroxyvitamin D (25OHD). If their level is
less than 20 ng/ml (deficiency), they will be invited to participate in Phase 2. A small
sample of participants with a level >= 20 ng/ml will also be invited to participate in Phase
2, to maintain participant blinding. Participation ends for the remaining women whose level
is 20 ng/ml or higher. During Phase 2, deficient women receive a blinded dose of 50,000 IU of
vitamin D supplementation per week. The small group of sufficient women will receive a
placebo. Participants will not be told what their 25OHD level was or what group they are in.
Women will be followed for three more menstrual cycles. In the presupplementation cycle and
in the last of these three cycles, the supplemented cycle , women will collect daily urine
specimens. Hormone levels will be compared between the pre-and postsupplementation cycles as
the primary analysis. A secondary analysis will compare the supplemented cycles in the
deficient women who received 50,000 IU and the deficient women who received placebo.
The original design of this trial included a low-dose (4,200 IU) vitamin D supplementation
arm. At entry into Phase 2, participants were randomized to receive the 4,200 IU vitamin D
supplement or 50,000 IU vitamin D supplement in a 2:3 ratio. The low-dose arm of the trial
has been discontinued for cost and efficiency purposes. As of 12/13/22, 16 participants were
randomized to receive the low-dose vitamin D supplement. On approval of the current document,
this information will be updated to reflect the final count of participants who received the
low-dose vitamin D supplement and the specific date at which the low-dose arm was
discontinued via a future amendment. Study data for women who received the low-dose vitamin D
supplement will be retained for research and analysis. Specific analyses, biospecimen use,
and statistical comparisons will not differ from those described below for the participants
who receive the 50,000 IU vitamin D supplement or the placebo. All data handling and security
procedures described in this document equivalently apply to data collected from participants
receiving the low-dose vitamin D supplement.
The primary aim of this trial will test the following hypotheses by comparing vitamin D
supplemented cycles to the presupplementation cycles, within-woman: (1) Mid-luteal
progesterone is higher in vitamin D supplemented cycles; (2) Rate of estrogen rise is higher
in vitamin D supplemented cycles; (3) Pre-ovulatory LH is higher in vitamin D supplemented
cycles.
Objectives:
Primary objective:
-To examine the effect of vitamin D supplementation on hypothalamic-pituitary-ovarian axis
hormones. We will evaluate the extent to which vitamin D supplementation:
- Increases urinary mid-luteal progesterone (an indicator of healthy, fertile follicle
development)
- Increases the rate of rise in urinary follicular phase estrogen (an indicator of
follicular development)
- Increases urinary pre-ovulatory LH (an indicator of healthy ovarian-hypothalamic
interaction)
Secondary objectives:
- Determine the impact of vitamin D supplementation in reproductive-aged women by assaying
the metabolome before and after vitamin D supplementation
- To quantify the increase in 25OHD and the fraction who achieve a level of 40 ng/ml after
1.5 and 3 months of supplementation, in response to 50,000 IU/week of vitamin D.
- To examine the effects of vitamin D supplementation on endometrial stromal cell
decidualization
Tertiary/Exploratory objectives:
- To examine the change in whole blood metals levels in response to vitamin D
supplementation.
- To examine the change in vaginal or oral microbiome in response to vitamin D
supplementation.
- To investigate the extent to which vitamin D reduces the incidence of
--delayed ovulation (follicular phase >20 days), 2) short luteal phase (<=10 days), and
3) long cycles (>34 days)
- To investigate the association between 25OHD levels, sleep measures, physical activity,
exposure to white/red/green/blue light, and hypothalamic-pituitary-ovarian axis
hormones.
Endpoints:
Primary Endpoint: Mid-luteal progesterone, follicular estrogen, preovulatory LH
Secondary Endpoints: Untargeted metabolomics, 25OHD, endometrial stromal cell function,
Tertiary Endpoints: metals, microbiome, ovulation, menstrual cycle length, sleep
