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

NCT03792984 | Completed Phase 3 DMC

• 1 other identifier: Ph-CT-2685
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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).

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency/Insufficiency

Keywords

Polycystic Ovary Syndrome; Calcium; Vitamin D; Metformin

Outcome Measures

Primary Outcomes (3)

• Change in quantitative insulin sensitivity check index (QUICKI).

  Assessment of QUICKI index at baseline and after 8 weeks of intervention.

  baseline, 8 weeks weeks.

• Change in Raynaud's index.

  Assessment of Raynaud's index at baseline and after 8 weeks of intervention.

  baseline, 8 weeks weeks.

• Change in McAuley Index.

  Assessment of McAuley Index at baseline and after 8 weeks of intervention.

  baseline, 8 weeks weeks.

Secondary Outcomes (25)

• Change in glucose concentration.

  baseline, 8 weeks.

• Change in insulin concentration.

  baseline, 8 weeks.

• Change in homeostasis model assessment of insulin resistance index (HOMA-IR).

  baseline, 8 weeks.

• Change in homeostasis model assessment of β-cell function index (HOMA-B).

  baseline, 8 weeks.

• Change in menstrual cycle abnormalities.

  up to 8 weeks.

Study Arms (2)

Metformin + Placebo

PLACEBO COMPARATOR

Drug: Metformin; Drug: Placebo

Calcium carbonate + Vitamin D3 + Metformin

EXPERIMENTAL

Dietary Supplement: Vitamin D3; Dietary Supplement: Calcium Carbonate; Drug: Metformin

Interventions

Vitamin D3 DIETARY_SUPPLEMENT

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

Calcium carbonate + Vitamin D3 + Metformin

Calcium Carbonate DIETARY_SUPPLEMENT

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

Calcium carbonate + Vitamin D3 + Metformin

Metformin 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.

Calcium carbonate + Vitamin D3 + Metformin; Metformin + Placebo

Placebo DRUG

PO for 8 weeks.

Metformin + Placebo

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Damascus University: lead

Study Sites (2)

Damascus University of Obstetrics and Gynecology Hospital

Damascus, Syria

Location

Orient Hospital

Damascus, Syria

Location

Related Publications (10)

• 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.

  PMID: 23789983 BACKGROUND

• 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.

  PMID: 17177140 BACKGROUND

• 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.

  PMID: 24933120 BACKGROUND

• Krul-Poel YH, Snackey C, Louwers Y, Lips P, Lambalk CB, Laven JS, Simsek S. The role of vitamin D in metabolic disturbances in polycystic ovary syndrome: a systematic review. Eur J Endocrinol. 2013 Oct 23;169(6):853-65. doi: 10.1530/EJE-13-0617. Print 2013 Dec.

  PMID: 24044903 BACKGROUND

• 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.

  PMID: 21550088 BACKGROUND

• Ott J, Wattar L, Kurz C, Seemann R, Huber JC, Mayerhofer K, Vytiska-Binstorfer E. Parameters for calcium metabolism in women with polycystic ovary syndrome who undergo clomiphene citrate stimulation: a prospective cohort study. Eur J Endocrinol. 2012 May;166(5):897-902. doi: 10.1530/EJE-11-1070. Epub 2012 Feb 13.

  PMID: 22330149 BACKGROUND

• Pal L, Zhang H, Williams J, Santoro NF, Diamond MP, Schlaff WD, Coutifaris C, Carson SA, Steinkampf MP, Carr BR, McGovern PG, Cataldo NA, Gosman GG, Nestler JE, Myers E, Legro RS; Reproductive Medicine Network. Vitamin D Status Relates to Reproductive Outcome in Women With Polycystic Ovary Syndrome: Secondary Analysis of a Multicenter Randomized Controlled Trial. J Clin Endocrinol Metab. 2016 Aug;101(8):3027-35. doi: 10.1210/jc.2015-4352. Epub 2016 May 17.

  PMID: 27186859 BACKGROUND

• 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.

  PMID: 20711952 BACKGROUND

• 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.

  PMID: 10487660 BACKGROUND

• 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.

  PMID: 31354810 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency

Interventions

Cholecalciferol; Calcium Carbonate; Metformin

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; Calcium Compounds; Inorganic Chemicals; Carbonates; Carbonic Acid; Carbon Compounds, Inorganic; Minerals; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Sally Kadoura, B Pharm, MD

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

  PRINCIPAL INVESTIGATOR

• Abdul Hakim Nattouf, MD, PhD

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

  STUDY DIRECTOR

• Marwan Alhalabi, MD, PhD

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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2018
• First Posted: January 4, 2019
• Study Start: December 1, 2016
• Primary Completion: October 1, 2017
• Study Completion: December 30, 2017
• Last Updated: June 6, 2019

Record last verified: 2018-12

Locations

SY (2)