The Effect of Calcium and Vitamin D Supplements on Metabolic and Hormonal Disturbances in Polycystic Ovary Syndrome Patients

NCT ID: NCT03792984

Last Updated: 2019-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-12-01
• Study Completion Date: 2017-12-30

Brief Summary

The aim of this study is to investigate the safety and metabolic-hormonal efficiency of supplementation vitamin D deficient/insufficient PCOS women with (calcium +vitamin D + metformin) for 8 weeks compared to (placebo+ metformin).

Detailed Description

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among females of reproductive age. The main manifestations of this syndrome are ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Noticeably, PCOS is associated with several metabolic disturbances such as insulin resistance, compensatory hyperinsulinemia, dyslipidemia and central obesity, which increase the risk for long-term complications like type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Moreover, previous data demonstrated that, compared to normo-ovulatory women, PCOS patients might exhibit a dysregulation in the IGF system represented as an elevation in the serum levels of free Insulin-like growth factor-1 (IGF-1) and a reduction in the serum levels of Insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact aetiology of PCOS remains unclear and current treatments are only moderately effective at controlling PCOS symptoms and preventing its complications. Growing evidence suggests a role of vitamin D in female reproductive diseases as the expression of Vitamin D Receptors (VDR) was identified in many organs throughout the female reproductive tract. On the top of that, vitamin D regulates over 300 genes, including genes that are important for glucose and lipid metabolism. Moreover, vitamin D deficiency is a common condition among women with PCOS, and several studies indicated an association between low levels of serum 25-hydroxyvitamin D (25-OH-Vitamin D) and manifestations of PCOS including insulin resistance, hyperandrogenism, and infertility. Further, a recent in-vitro study showed that vitamin D regulated steroidogenesis and IGFBP-1 production in cultured human ovarian cells, and many reports have suggested an interrelation between IGF-1 and vitamin D.

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency/Insufficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Metformin + Placebo

Group Type: PLACEBO_COMPARATOR

Metformin

Intervention Type: DRUG

Metformin (1500 mg/daily; the metformin dose was increased stepwise, starting with 500 mg once daily for the 1st week, 500 mg twice daily in the 2nd week, followed by 500 mg 3 times daily from the 3rd week onward). PO for 8 weeks.

Placebo

Intervention Type: DRUG

PO for 8 weeks.

Calcium carbonate + Vitamin D3 + Metformin

Group Type: EXPERIMENTAL

Vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

Vitamin D3 (Cholecalciferol) (6000 IU/daily). PO for 8 weeks.

Calcium Carbonate

Intervention Type: DIETARY_SUPPLEMENT

Calcium carbonate (1000 mg/daily). PO for 8 weeks.

Metformin

Intervention Type: DRUG

Metformin (1500 mg/daily; the metformin dose was increased stepwise, starting with 500 mg once daily for the 1st week, 500 mg twice daily in the 2nd week, followed by 500 mg 3 times daily from the 3rd week onward). PO for 8 weeks.

Interventions

Vitamin D3

Vitamin D3 (Cholecalciferol) (6000 IU/daily). PO for 8 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Calcium Carbonate

Calcium carbonate (1000 mg/daily). PO for 8 weeks.

Intervention Type: DIETARY_SUPPLEMENT

Metformin

Metformin (1500 mg/daily; the metformin dose was increased stepwise, starting with 500 mg once daily for the 1st week, 500 mg twice daily in the 2nd week, followed by 500 mg 3 times daily from the 3rd week onward). PO for 8 weeks.

Intervention Type: DRUG

Placebo

PO for 8 weeks.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• PCOS women aged 18-30 years diagnosed according to the Rotterdam criteria.
• Vitamin D deficiency or insufficiency according to the Endocrine Society Clinical Practice Guideline.
• Normal liver function.
• Normal kidney function.

Exclusion Criteria

• Pregnant, postpartum or breastfeeding women.
• Females aged <18 or >30 years old.
• Patients who were diagnosed with androgen-secreting tumours, Cushing's syndrome, congenital adrenal hyperplasia, hyperprolactinemia, hypercalcemia, malabsorption disorders, diabetes mellitus, thyroid disorders, liver disease, renal disease, epilepsy, cardiovascular disease.
• History of kidney stones.
• Usage of any hormonal therapy, corticosteroids (other than topical corticosteroids forms), insulin sensitizers, hypolipidemic agents, anti-obesity medications, vitamin D or calcium supplements, anti-epileptic drugs, or any other drugs known to affect endocrine parameters, carbohydrate metabolism, or calciotropic hormone concentrations during the last 3 months.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 30 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Damascus University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sally Kadoura, B Pharm, MD

Role: PRINCIPAL_INVESTIGATOR

Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria

Abdul Hakim Nattouf, MD, PhD

Role: STUDY_DIRECTOR

Professor at Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Damascus University, Damascus, Syria

Marwan Alhalabi, MD, PhD

Role: STUDY_DIRECTOR

Professor at Department of Embryology and Reproductive Medicine, Faculty of Medicine, Damascus University, Damascus, Syria.

Locations

Damascus University of Obstetrics and Gynecology Hospital

Damascus, , Syria

Orient Hospital

Damascus, , Syria

Countries

Syria

References

Ameri P, Giusti A, Boschetti M, Murialdo G, Minuto F, Ferone D. Interactions between vitamin D and IGF-I: from physiology to clinical practice. Clin Endocrinol (Oxf). 2013 Oct;79(4):457-63. doi: 10.1111/cen.12268. Epub 2013 Aug 9.

Reference Type: BACKGROUND

PMID: 23789983 (View on PubMed)

Hahn S, Haselhorst U, Tan S, Quadbeck B, Schmidt M, Roesler S, Kimmig R, Mann K, Janssen OE. Low serum 25-hydroxyvitamin D concentrations are associated with insulin resistance and obesity in women with polycystic ovary syndrome. Exp Clin Endocrinol Diabetes. 2006 Nov;114(10):577-83. doi: 10.1055/s-2006-948308.

Reference Type: BACKGROUND

PMID: 17177140 (View on PubMed)

Irani M, Merhi Z. Role of vitamin D in ovarian physiology and its implication in reproduction: a systematic review. Fertil Steril. 2014 Aug;102(2):460-468.e3. doi: 10.1016/j.fertnstert.2014.04.046. Epub 2014 Jun 3.

Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 24044903 (View on PubMed)

Li HW, Brereton RE, Anderson RA, Wallace AM, Ho CK. Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome. Metabolism. 2011 Oct;60(10):1475-81. doi: 10.1016/j.metabol.2011.03.002. Epub 2011 May 6.

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Parikh G, Varadinova M, Suwandhi P, Araki T, Rosenwaks Z, Poretsky L, Seto-Young D. Vitamin D regulates steroidogenesis and insulin-like growth factor binding protein-1 (IGFBP-1) production in human ovarian cells. Horm Metab Res. 2010 Sep;42(10):754-7. doi: 10.1055/s-0030-1262837. Epub 2010 Aug 13.

Reference Type: BACKGROUND

PMID: 20711952 (View on PubMed)

Thierry van Dessel HJ, Lee PD, Faessen G, Fauser BC, Giudice LC. Elevated serum levels of free insulin-like growth factor I in polycystic ovary syndrome. J Clin Endocrinol Metab. 1999 Sep;84(9):3030-5. doi: 10.1210/jcem.84.9.5941.

Reference Type: BACKGROUND

PMID: 10487660 (View on PubMed)

Kadoura S, Alhalabi M, Nattouf AH. Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Menstrual Cycle Abnormalities, Hormonal Profile, and IGF-1 System in Polycystic Ovary Syndrome Patients: A Randomized, Placebo-Controlled Clinical Trial. Adv Pharmacol Sci. 2019 Jul 1;2019:9680390. doi: 10.1155/2019/9680390. eCollection 2019.

Reference Type: DERIVED

PMID: 31354810 (View on PubMed)

Other Identifiers

Ph-CT-2685

Identifier Type: -

Identifier Source: org_study_id