Clinical trial NCT04355572: Evaluation of the Clinical and Psychological Impact of Vitamin D Replacement in Adolescent Females at Risk for Polycystic Ovarian Syndrome (PCOS)
Official title: Evaluation of the Clinical and Psychological Impact of Vitamin D Replacement in Adolescent Females at Risk for Polycystic Ovarian Syndrome (PCOS)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Polycystic Ovarian Syndrome in Adolescent Females
Vitamin D Deficiency
Keywords: Anti-Mullerian Hormone (AMH)
Lead sponsor: Yale University
Sponsor class: OTHER
First posted: 2020-04-21
Enrollment: 60
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a double blind, placebo controlled, randomized trial of study subjects with PCOS and low vitamin D to 2 groups- placebo and vitamin D replacement. Participants and investigators will be blinded to treatment modality until the end of the trial period

Detailed description: Patients referred to the pediatric endocrinology clinic or adolescent gynecology clinic at Yale New Haven Children Hospital with a primary complaint of hirsutism, acne, or amenorrhea and/or oligomenorrhea persisting 2 years after their menarche will be evaluated for polycystic ovarian syndrome through history, physical exam, pelvic ultrasound, and laboratory evaluation, to include androgen testing, thyroid testing, female hormone testing, and diabetic risk testing (this is standard of care). A vitamin D level will also be drawn. While vitamin D level is not currently part of the diagnostic algorithm for PCOS, it is not unreasonable to check in patients in which there is concern for an endocrine disorder. If the patient meets Rotterdam criteria and their serum vitamin D level is between 6 and 29 ng/mL, the patient and their guardian(s) will be approached for inclusion in our study by the physician or dedicated research nursing staff.

If patient and guardian agree to participate and sign a consent / assent form, the patient will then be randomized to receive vitamin D supplement versus placebo and will be followed for 6 months on their randomized replacement with repeat laboratory testing of AMH, vitamin D, lipid profile, glucose and insulin testing, androgen testing, and female hormone testing at the randomization, 3 months and at the end of the course of the trial(6 months). Patients with vitamin D levels 5ng/mL or less will not be randomized, they will be given recommended treatment. Depressive symptoms will be assessed at time of randomization, 3 months post randomization, and 6 months post randomization using the Beck Depression Inventory-II, the gold standard self-report depression inventory. A depression screen is currently administered to all adolescents seen at Yale New Haven Children Hospital outpatient clinics with a protocol for patients who report clinically significant levels of depression. This protocol will remain in place and will not be altered during this research study.

After post-trial testing, patients will be unblinded and patients who still have vitamin D below threshold will be offered vitamin D treatment.

Aim 1: To investigate the effect of vitamin D replacement upon biochemical parameters of polycystic ovarian syndrome (PCOS) in adolescent female patients. Hypothesis: Replacement of vitamin D to normal levels in adolescents with PCOS and/or at risk for PCOS and low levels of vitamin D will lower serum androgen and anti-mullerian hormone (AMH) levels.

Aim 2: To investigate the effect of vitamin D replacement on clinical features of PCOS in adolescent female patients. Hypothesis: Replacement of vitamin D in adolescents with PCOS and/or at risk for PCOS and low levels of vitamin D will improve symptoms of menstrual irregularities, acne, and hirsutism.

Aim3: To investigate the effect of vitamin D replacement on depressive symptoms in adolescent female patients with PCOS. Hypothesis: Replacement of vitamin D in adolescents with PCOS or at risk for PCOS and low levels of serum vitamin D will improve symptoms of depression.

Eligibility criteria: Inclusion Criteria:

- Postmenarchal adolescent females aged 13-21 who meet modified Rotterdam criteria for PCOS, with a serum vitamin D level between 6-29 ng/mL.

Exclusion Criteria:

* Other causes for hyperandrogenism,
* Chronic renal diseases,
* Acquired or inherited calcium and vitamin D metabolic disorders.

Primary outcomes:
measure: Change in oligomenorrhea
timeFrame: 6 months
measure: Changes Vitamin D (25-hydroxyvitamin D) level
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
Secondary outcomes:
measure: Change in DHEAS level
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
measure: Changes in Androstenedione level
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
measure: Change in Anti-Mullerian hormone (AMH) level
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
measure: Change in testosterone level
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
measure: Change in Hirsutism
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
measure: Change Body Acne
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
measure: Change in Facial
timeFrame: at enrollment, at 3 months after randomization and 6 months after randomization
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Children's Hospital
state: Connecticut
Study officials:
affiliation: Yale University
name: Alla Vash-Margita, MD
role: PRINCIPAL_INVESTIGATOR
References: