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The Effects of Vitamin D on Transforming Growth Factor-beta1 in Polycystic Ovary Syndrome

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ClinicalTrials.gov Identifier: NCT02460380
Recruitment Status : Completed
First Posted : June 2, 2015
Last Update Posted : June 2, 2015
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 transforming growth factor-β (TGF-β) dysregulation may be implicated. TGF-β is the prototype member of the TGF-β superfamily of proteins. TGF-βs 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 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. 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 levels in several diseases where TGF-β1 is elevated, including myelofibrosis. Therefore, the investigators hypothesize that vitamin D treatment of PCOS women will result in a decrease of serum TGF-β1 levels concomitant with improvement in clinical disease parameters. In addition, the investigators hypothesize that improvement in clinical disease parameters will correlate with changes in TGF-β1 bioavailability. Our aim in the present study is to investigate the effects of vitamin D treatment on serum TGF-β1/sENG levels in PCOS women, and assess whether changes in TGF-β1/sENG levels 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 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 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 on Transforming Growth Factor-beta1 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 serum TGF-β1 and sENG levels [ Time Frame: 8 weeks ]
    Serum TGF-β1/sENG as a measure of TGF-β1 bioavailability


Secondary Outcome Measures :
  1. The effects of vitamin D3 on clinical disease parameters in women with PCOS [ Time Frame: 4 months ]
    Interval between periods as a measure ovulatory dysfunction

  2. The effects of vitamin D3 on clinical disease parameters in women with PCOS [ Time Frame: 4 months ]
    Blood pressure

  3. The effects of vitamin D3 on clinical disease parameters in women with PCOS [ Time Frame: 8 weeks ]
    HOMA IR as a measure of insulin resistance

  4. The effects of vitamin D3 on clinical disease parameters in women with PCOS [ Time Frame: 8 weeks ]
    Free testosterone

  5. The effects of vitamin D3 on clinical disease parameters in women with PCOS [ Time Frame: 8 weeks ]
    lipid profile

  6. The effects of vitamin D3 on clinical disease parameters in women with PCOS [ Time Frame: 4 months ]
    Ferriman-Gallwey score as a measure of hirsutism


Other Outcome Measures:
  1. Correlation between the changes in TGF-β1 and/or sENG and/or TGF-β1/sENG with the changes in PCOS clinical parameters following vitamin D3 supplementation. [ Time Frame: 8 weeks ]
    Correlation between changes in serum TGF-β1/sENG and changes in lipid profile.

  2. Correlation between the changes in TGF-β1 and/or sENG and/or TGF-β1/sENG with the changes in PCOS clinical parameters following vitamin D3 supplementation. [ Time Frame: 4 months ]
    Correlation between changes in serum TGF-β1/sENG and changes in the interview between periods.

  3. Correlation between the changes in TGF-β1 and/or sENG and/or TGF-β1/sENG with the changes in PCOS clinical parameters following vitamin D3 supplementation. [ Time Frame: 4 months ]
    Correlation between changes in serum TGF-β1/sENG and changes in the Ferriman-Gallwey score.

  4. Correlation between the changes in TGF-β1 and/or sENG and/or TGF-β1/sENG with the changes in PCOS clinical parameters following vitamin D3 supplementation. [ Time Frame: 4 months ]
    Correlation between changes in serum TGF-β1/sENG and changes in blood pressure.

  5. Correlation between the changes in TGF-β1 and/or sENG and/or TGF-β1/sENG with the changes in PCOS clinical parameters following vitamin D3 supplementation. [ Time Frame: 8 weeks ]
    Correlation between changes in serum TGF-β1/sENG and changes in HOMA-IR.

  6. Correlation between the changes in TGF-β1 and/or sENG and/or TGF-β1/sENG with the changes in PCOS clinical parameters following vitamin D3 supplementation. [ Time Frame: 8 weeks ]
    Correlation between changes in serum TGF-β1/sENG and changes in free testosterone.



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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
  • Diagnosed with poor ovarian reserve (AMH<1ng/mL).

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
Last Update Posted: June 2, 2015
Last Verified: May 2015

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
Mitogens
Micronutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action