The Investigation of Vitamin D and Menstrual Cycles Trial, the inVitD Trial: A Phase II Clinical Trial

NCT05050916 | Completed Phase 2

• 2 other identifiers: 10000476000476-E
• Study Type: interventional
• Target: 57
• Locations: 1 country
• Sites: 2

Brief 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 have low vitamin D and move to Phase 2 will receive 50000 IU//week of vitamin D supplement. Participants who do not have low vitamin D will receive placebo. If they have low vitamin D, 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 self-administer 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).

Conditions

Reproductive Issues

Keywords

reproductive; Health; Female; Hormones; period

Outcome Measures

Primary Outcomes (1)

• To examine the effect of vitamin D supplementation on hypothalamic-pituitary-ovarian axis hormones.

  We will evaluate the extent to which vitamin D supplementation: 1) Increases urinary mid-luteal progesterone (an indicator of healthy, fertile follicle development) 2) Increases the rate of rise in urinary follicular phase estrogen (an indicator of follicular development) 3) Increases urinary pre-ovulatory LH (an indicator of healthy ovarian-hypothalamic interaction)

  60 months

Secondary Outcomes (5)

• 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.

  60 months

• To investigate the effect of vitamin D supplementation on the microbiome

  60 months

• To investigate the effect of vitamin D supplementation on endometrial stromal cell function.

  60 months

• To examine the change in whole blood metals levels in response to vitamin D supplementation.

  60 months

• Determine the impact of Vitamin D supplementation in reproductive-aged women by assaying the metabolome before and after vitamin D supplementation.

  60 months

Study Arms (3)

1/High Dose Vitamin D

EXPERIMENTAL

Deficient participants will be assigned to the Endocrine Society recommendation for deficiency, 50,000 IU/week.

Dietary Supplement: Vitamin D

2/Placebo

PLACEBO COMPARATOR

Participants with sufficient levels of vitamin D will receive placebo instead of Vitamin D supplementation.

Other: Placebo

3/Low Dose Vitamin D

EXPERIMENTAL

Early in the study, deficient participants were randomized to either the U.S. recommended daily allowance, 4200 IU/week or the high dose vitamin D arm. The low dose arm was discontinued mid-way through the trial and all deficient participants were assigned to the high dose arm.

Dietary Supplement: Vitamin D

Interventions

Vitamin D DIETARY_SUPPLEMENT

The High Dose Vitamin D arm will receive 50,000 IU/week of cholecalciferol. The Low Dose Vitamin D arm will receive 4,200 IU/week of cholecalciferol

1/High Dose Vitamin D; 3/Low Dose Vitamin D

Placebo OTHER

Cellulose capsule

2/Placebo

Eligibility Criteria

• Age: 19 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Having natural, spontaneous menstrual cycles (no hormonal therapy) less than 50 days in length.
• Aged 19-40 years
• Ability to take a vitamin D capsule and willing to adhere to the weekly regimen
• If sexually active, use of a non-hormonal contraceptive method.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• No menstrual period in the last 50 days, or, a typical menstrual cycle length \<16 or \>49 days.
• Use of a vitamin D supplement for more than one month and on more than 15 days out of each month. Volunteers will be asked to check their supplement label for vitamin D content.
• Unwilling to abstain from taking non-study vitamin D supplements during the study or if already taking a medically-advised vitamin D supplement.
• Use of a calcium supplement (including certain antacids) and unwilling to abstain from taking a calcium supplement during the study.
• Known polycystic ovarian syndrome
• Depo-provera use in the previous 12 months
• Current use of any hormones, including birth control
• Current use of a hormonal intrauterine device (IUD)
• Current pregnancy or lactation, trying to become pregnant, or planning to try in the next four menstrual cycles or 5 months.
• History of seizure disorders
• Celiac disease
• Crohn s Disease
• Body mass index \>35
• Aged \<19 or \> 40 years

Sponsors & Collaborators

• National Institute of Environmental Health Sciences (NIEHS): lead

Study Sites (2)

Henry Ford Health System

Detroit, Michigan, 48187, United States

Location

NIEHS Clinical Research Unit (CRU)

Research Triangle Park, North Carolina, 27709, United States

Location

Related Publications (1)

• Metz CN, Chatterjee PK, Hyman N, Busch S, Tarasenko SA, Hoofnagle AN, Gregersen PK, Steiner AZ, Jukic AMZ. Leveraging menstrual effluent (ME) to investigate vitamin D and human decidualization, a potential link with fertility. J Clin Endocrinol Metab. 2026 Jan 5:dgaf708. doi: 10.1210/clinem/dgaf708. Online ahead of print.

  PMID: 41492807 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Vitamin D

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Anne Marie Z Jukic, Ph.D.

  National Institute of Environmental Health Sciences (NIEHS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 18, 2021
• First Posted: September 21, 2021
• Study Start: March 17, 2023
• Primary Completion: June 7, 2024
• Study Completion: June 27, 2024
• Last Updated: February 13, 2026

Record last verified: 2024-07-09

Locations

US (2)