ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02460380
Recruitment Status : Completed
First Posted : June 2, 2015
Results First Posted : September 14, 2018
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Richard Grazi, Maimonides Medical Center

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.


Condition or disease Intervention/treatment Phase
Polycystic Ovary Syndrome Vitamin D Deficiency Drug: Vitamin D3 Other: Placebo Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 93 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: The Effects of Vitamin D Supplementation on Transforming Growth Factor-beta1 and Vascular Endothelial Growth Factor in Vitamin D-Deficient Women With Polycystic Ovary Syndrome: A Randomized Placebo-Controlled Trial
Study Start Date : October 2013
Actual Primary Completion Date : March 2015
Actual Study Completion Date : March 2015


Arm Intervention/treatment
Active Comparator: Vitamin D3
Women allocated to vitamin D3 group received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks.
Drug: Vitamin D3
Women allocated to vitamin D arm received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks.

Placebo Comparator: Placebo
Women in the placebo group received once capsule of placebo once weekly for eight weeks.
Other: Placebo
Women in the placebo arm received once capsule of placebo once weekly for eight weeks




Primary Outcome Measures :
  1. Effect of Vitamin D on Angiogenic Factors [ Time Frame: Baseline (pre-treatment) and 8 weeks later (post-treatment) ]
    Serum TGF-β1/sENG ratio as a measure of TGF-β1 bioavailability

  2. Effect of Vitamin D on Angiogenic Factors [ Time Frame: Baseline (pre-treatment) and 8 weeks later (post-treatment) ]
    Serum VEGF level


Secondary Outcome Measures :
  1. The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: Baseline (pre-treatment) and 4 months later (two months after the completion of treatment) ]
    Interval between periods as a measure ovulatory dysfunction

  2. The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: Baseline (pre-treatment) and 4 months later (two months after the completion of treatment) ]
    Blood pressure

  3. The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: Baseline (pre-treatment) and 8 weeks later (post-treatment) ]
    The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance. Insulin resistance is a condition in which cells fail to respond to the normal actions of the hormone insulin. The HOMA index was calculated as the product of fasting plasma blood glucose and insulin divided by 22.5.

  4. The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: Baseline (pre-treatment) and 8 weeks later (post-treatment) ]
    Free testosterone

  5. The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: Baseline (pre-treatment) and 8 weeks later (post-treatment) ]
    Lipid profile

  6. The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: Baseline (pre-treatment) and 4 months later (two months after the completion of treatment) ]
    Ferriman-Gallwey score is a method used to assess and quantify hirsutism in women. A total score < 8 is considered normal whereas a score of 8 to 15 indicates mild hirsutism. A score >15 indicates moderate or severe hirsutism.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 38 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Richard Grazi, Director of Genesis Fertility and Reproductive Medicine, Obstetrics and Gynecology, Maimonides Medical Center
ClinicalTrials.gov Identifier: NCT02460380     History of Changes
Other Study ID Numbers: 2013-06-03
First Posted: June 2, 2015    Key Record Dates
Results First Posted: September 14, 2018
Last Update Posted: October 12, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Syndrome
Polycystic Ovary Syndrome
Vitamin D Deficiency
Disease
Pathologic Processes
Ovarian Cysts
Cysts
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Gonadal Disorders
Endocrine System Diseases
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Endothelial Growth Factors
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents