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Trial record 42 of 122 for:    hypertension "vitamin d"

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

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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

Tracking Information
First Submitted Date  ICMJE May 23, 2015
First Posted Date  ICMJE June 2, 2015
Results First Submitted Date  ICMJE February 6, 2017
Results First Posted Date  ICMJE September 14, 2018
Last Update Posted Date October 12, 2018
Study Start Date  ICMJE October 2013
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 17, 2018)
  • 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
  • Effect of Vitamin D on Angiogenic Factors [ Time Frame: Baseline (pre-treatment) and 8 weeks later (post-treatment) ]
    Serum VEGF level
Original Primary Outcome Measures  ICMJE
 (submitted: May 28, 2015)
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
Change History Complete list of historical versions of study NCT02460380 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 17, 2018)
  • 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
  • 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
  • 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.
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 28, 2015)
  • 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
  • The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: 4 months ]
    Blood pressure
  • 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
  • The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: 8 weeks ]
    Free testosterone
  • The Effects of Vitamin D3 on Clinical Disease Parameters in Women With PCOS [ Time Frame: 8 weeks ]
    Lipid profile
  • 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures
 (submitted: May 28, 2015)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
 
Descriptive Information
Brief Title  ICMJE The Effects of Vitamin D on Angiogenic Factors in Women With Polycystic Ovary Syndrome
Official Title  ICMJE 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
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.

Detailed Description

This study is a randomized, single blind, placebo-controlled trial to evaluate the effect of vitamin D on vitamin D-deficient women with PCOS. 93 reproductive-aged women diagnosed with PCOS presenting to Maimonides Medical Center for annual check-up between October 2013 and March 2015 were screened for vitamin D deficiency (defined as 25 hydroxy-vitaminD [25OH-D] levels <20 ng/mL). All participants signed the informed consent and the study was approved by the international review board (IRB) of Maimonides Medical Center. PCOS was diagnosed according to the Rotterdam Consensus (ESHRE/ASRM criteria), i.e. the presence of two of three criteria: oligo- or anovulation, signs of clinical hyperandrogenism, and/or biochemical signs of hyperandrogenism and polycystic ovaries on ultrasonography after exclusion of specific identifiable disorders (thyroid disorder, hyperprolactinemia, congenital adrenal hyperplasia, androgen-secreting tumors, and Cushing's syndrome). The investigators included women aged between 18 and 38 years who were not: 1) pregnant, postpartum, breastfeeding, or 2) taking any vitamin D supplements, metformin or any hormonal therapy.

Interventions and blood collection:

68 women diagnosed with PCOS and vitamin D deficiency were enrolled. Participants were allocated to each group according to a computer-generated list using ratio 2/1 (Vitamin D/placebo). Women allocated to vitamin D group received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks. The vitamin D supplementation regimen was extracted from the Endocrine Society guidelines. Women in the placebo group received once capsule of placebo once weekly for eight weeks. The placebo was prepared at Maimonides Medical Center's pharmacy. To ensure compliance, The investigators called each participant once weekly and reminded her to take her pill. Fasting blood samples were collected by venipuncture before starting and within two weeks after completing the treatment (vitamin D or placebo). Blood samples were allowed to clot for 30 minutes at room temperature before centrifugation at 1,200 rpm for 10 minutes. Serum was stored at -80°C in aliquots until assayed.

The assays of all measured hormones, 25OH-D, VEGF, TGF-β1, sENG, and AMH:

Serum 25OH-D levels were measured before and after completing the treatment. The levels were determined by the ADVIA Centaur vitamin D assay (Siemens Healthcare Diagnostics). Dehydroepiandrosterone sulfate (DHEAS), testosterone, sex hormone-binding globulin (SHBG), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were measured using IMMULITE 2000 XPi immunoassay system (Siemens Healthcare USA). Insulin and prolactin concentrations were quantified by DXL 800 immunoassay analyzer according to manufacturer's protocols (Beckman Coulter). Insulin resistance was calculated according to the homeostatic model assessment (HOMA) (29) by using the following formula: Insulin resistance (HOMA IR) = [fasting insulin (µU/mL) x fasting glucose (mmol/L)]/22.5. 17OH-progesterone level was determined by ELISA assay (Eagle BioSciences). AMH concentration was measured using the ultrasensitive AMH/MIS CLIA kit (AnshLabs). TGF-β1 concentration was measured using Human TGF-beta1 Quantikine ELISA kit according to manufacturer's protocols (R&D Systems). sENG levels were quantified by Human Endoglin/CD105 Quantikine ELISA kit (R&D Systems). VEGF concentration was quantified using Human VEGF Quantikine ELISA kit according to manufacturer's protocols (R&D Systems). The inter-assay and intra-assay coefficients of variation for all assays were less than 10%.

Clinical parameters:

All the clinical parameters were evaluated before and four months after the completion of treatment. These parameters included blood pressure (BP), Ferriman-Gallwey score (FGS) (hirsutism score), acne status, and interval between periods.

Statistical analysis:

Data were tested for normality. All values were expressed as mean ± standard error of the mean (SEM). A paired student's t-test was used to compare pre- and post-treatment serum levels and clinical parameters. Correlation between changes in angiogenic factors and changes in clinical disease parameters was analyzed using Pearson's test and linear regression. X2-test was used to evaluate the changes in acne after treatment. SigmaStat (SPSS Science, Chicago, IL) was used for statistical analysis. P<0.05 was considered to be statistically significant.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Condition  ICMJE
  • Polycystic Ovary Syndrome
  • Vitamin D Deficiency
Intervention  ICMJE
  • Drug: Vitamin D3
    Women allocated to vitamin D arm received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks.
  • Other: Placebo
    Women in the placebo arm received once capsule of placebo once weekly for eight weeks
Study Arms  ICMJE
  • Active Comparator: Vitamin D3
    Women allocated to vitamin D3 group received one capsule 50.000 IU of vitamin D3 once weekly for eight weeks.
    Intervention: Drug: Vitamin D3
  • Placebo Comparator: Placebo
    Women in the placebo group received once capsule of placebo once weekly for eight weeks.
    Intervention: Other: Placebo
Publications * 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-β1 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 28, 2015)
93
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE March 2015
Actual Primary Completion Date March 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 38 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02460380
Other Study ID Numbers  ICMJE 2013-06-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Richard Grazi, Maimonides Medical Center
Study Sponsor  ICMJE Maimonides Medical Center
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Maimonides Medical Center
Verification Date September 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP