The Effects of Vitamin D on Angiogenic Factors in Women With Polycystic Ovary Syndrome

NCT02460380 | Completed Phase 4 Results

• 1 other identifier: 2013-06-03
• Study Type: interventional
• Target: 93
• Locations: 0 countries
• Sites: N/A

Brief Summary

Polycystic Ovary Syndrome (PCOS) affects 5 to 10% of women of reproductive age. It is characterized by a cluster of hyperandrogenism, hyperinsulinemia, menstrual dysfunction, hirsutism and infertility. Although the pathogenesis of PCOS is unknown, accumulating evidence suggests that the dysregulation of some angiogenic factors, such as transforming growth factor-β (TGF-β) and vascular endothelial growth factor (VEGF), may be implicated. TGF-βs and VEGF exert a diverse range of biological functions regulating cell proliferation, angiogenesis, fibroblast activation and tissue fibrosis. PCOS ovaries show all the hallmarks of TGF-β and VEGF upregulation, including increased collagen deposition in ovarian stroma and theca, supported by increased vascularity. Consistent with this, The investigators recently showed that TGF-β1 is increased in serum of PCOS women while its circulating receptor soluble endoglin (sENG) is decreased, resulting in greater TGF-β1 bioavailability. Furthermore, it has been shown that women with PCOS have increased VEGF levels in the serum and/or follicular fluid. PCOS patients also have decreased vitamin D levels, and vitamin D treatment has been previously shown to improve various clinical parameters in PCOS women, including glucose intolerance, hypertension and androgen levels. Interestingly, vitamin D has been shown to decrease TGF-β1 and VEGF levels in several diseases, including myelofibrosis and various human cancer cells. Therefore, the investigators hypothesize that vitamin D treatment of PCOS women will result in a decrease of serum TGF-β1 levels and/or VEGF levels concomitant with improvement in clinical disease parameters. In addition, the investigators hypothesize that improvement in clinical disease parameters will correlate with changes in serum VEGF levels and TGF-β1 bioavailability. Our aim in the present study is to investigate the effects of vitamin D treatment on serum VEGF and TGF-β1/sENG levels in PCOS women, and assess whether changes in these angiogenic factors following vitamin D treatment correlate with clinical disease in these women. For this end, PCOS patients who are vitamin D-deficient will be treated with vitamin D and their serum levels of VEGF, TGF-β1 and its sENG receptor will be measured before and after treatment. In addition, clinical disease parameters will be recorded before and 4 months after treatment, including serum glucose and insulin levels, serum androgen levels, and blood pressure. The proposed study aims to identify a putative link between vitamin D, VEGF, and TGF-β1 in the context of PCOS, and provide a novel molecular explanation for the beneficial clinical effects of vitamin D on PCOS patients.

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency

Outcome Measures

Primary Outcomes (2)

• Effect of Vitamin D on Angiogenic Factors

  Serum TGF-β1/sENG ratio as a measure of TGF-β1 bioavailability

  Baseline (pre-treatment) and 8 weeks later (post-treatment)

• Effect of Vitamin D on Angiogenic Factors

  Serum VEGF level

  Baseline (pre-treatment) and 8 weeks later (post-treatment)

Secondary Outcomes (6)

• The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS

  Baseline (pre-treatment) and 4 months later (two months after the completion of treatment)

• The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS

  Baseline (pre-treatment) and 4 months later (two months after the completion of treatment)

• The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS

  Baseline (pre-treatment) and 8 weeks later (post-treatment)

• The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS

  Baseline (pre-treatment) and 8 weeks later (post-treatment)

• The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS

  Baseline (pre-treatment) and 8 weeks later (post-treatment)

Study Arms (2)

Vitamin D3

ACTIVE COMPARATOR

Women allocated to vitamin D3 group received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks.

Drug: Vitamin D3

Placebo

PLACEBO COMPARATOR

Women in the placebo group received once capsule of placebo once weekly for eight weeks.

Other: Placebo

Interventions

Vitamin D3 DRUG

Women allocated to vitamin D arm received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks.

Vitamin D3

Placebo OTHER

Women in the placebo arm received once capsule of placebo once weekly for eight weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 38 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women with PCOS who have vitamin D deficiency (serum 25-hydroxyvitamin D\<20 ng/mL)

You may not qualify if:

• Pregnant, postpartum, breast feeding
• Taking Metformin, vitamin D, or any hormonal therapy

Sponsors & Collaborators

• Maimonides Medical Center: lead

Related Publications (1)

• Irani M, Seifer DB, Grazi RV, Julka N, Bhatt D, Kalgi B, Irani S, Tal O, Lambert-Messerlian G, Tal R. Vitamin D Supplementation Decreases TGF-beta1 Bioavailability in PCOS: A Randomized Placebo-Controlled Trial. J Clin Endocrinol Metab. 2015 Nov;100(11):4307-14. doi: 10.1210/jc.2015-2580. Epub 2015 Oct 20.

  PMID: 26485217 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Results Point of Contact

• Title: Mohamad Irani
• Organization: Maimonides Medical Center

mohamad.irani@hotmail.com

3472862167

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Genesis Fertility and Reproductive Medicine, Obstetrics and Gynecology

Study Record Dates

• First Submitted: May 23, 2015
• First Posted: June 2, 2015
• Study Start: October 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 12, 2018
• Results First Posted: September 14, 2018

Record last verified: 2018-09