The Combined Effect of N-Acetyl Cysteine and Metformin in Polycystic Ovary Syndrome Patients

NCT06836128 | Recruiting Phase 3 DMC

• 1 other identifier: Acetylcysteine in PCOS
• Study Type: interventional
• Target: 102
• Locations: 1 country
• Sites: 1

Brief Summary

The study aims to evaluate the effects of combination of metformin with NAC in PCOS on biochemical and hormonal parameters.

Conditions

Polycystic Ovary Syndrome

Keywords

PCOS; NAC; metformin

Outcome Measures

Primary Outcomes (1)

• Primary outcome will be change in LH/FSH levels.

  change in LH/FSH ratio

  3 months

Secondary Outcomes (4)

• improvement in hormonal levels in patients with PCOS

  3 months

• improvement in clinical features in patients with PCOS

  3 months

• improvement in biochemical parameters in patients with PCOS

  3 months

• improvement in metabolic parameters in patients with PCOS

  3 months

Study Arms (2)

Group-MN

EXPERIMENTAL

Group-MN, constituting 51 cases, will receive N-acetyl cysteine and metformin (600 mg three times daily of acetyl cysteine and 500 mg once daily for one week, then 500 mg twice daily for one week, and 500 mg three times daily thereafter of metformin)

Drug: N-acetyl cysteine; Drug: Metfomin

Group-M

EXPERIMENTAL

Group-M, constituting 51 cases, will receive treatment with metformin (starting with 500 mg once daily for one week, then 500 mg twice daily for one week, and 500 mg three times daily thereafter)

Drug: Metfomin

Interventions

N-acetyl cysteine DRUG

N-Acetyl Cysteine (NAC) has antioxidant properties and is essential for the body's production of glutathione, and both glutathione and NAC are potent antioxidants.

Also known as: NAC

Group-MN

Metfomin DRUG

metformin is commonly used for managing polycystic ovary syndrome (PCOS) due to its benefits in addressing several underlying features of the condition. While it is not officially approved by regulatory agencies like the FDA for PCOS, it is widely recognized and recommended in clinical practice guidelines as an off-label treatment for PCOS, particularly in women with insulin resistance and metabolic dysfunction.

Group-M; Group-MN

Eligibility Criteria

• Age: 20 Years - 45 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female aged 20 to 45 years old.
• Confirmed diagnosis with PCOS according to the 2023 International Evidence-based Guideline for the Assessment and Management of PCOS.
• Ability to give informed consent.

You may not qualify if:

• Hypersensitivity to either metformin or NAC.
• Consumption of medications affecting carbohydrate metabolism, such as insulin, sulfonylureas, and taking hormonal analogues two months prior to enrollment.
• Hyperprolactinemia, defined as a prolactin level above laboratory reference range.
• Diabetes mellitus.
• Thyroid dysfunction, subjects with elevated or low TSH level.
• Renal impairment where creatinine clearance (CrCl) less than 30 ml/min.
• Severe hepatic impairment, defined as significant biochemical abnormalities, including hypoalbuminemia and abnormal serum concentration (2-3 times the upper limit of normal), of at least two of the following liver function markers: total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT).
• Active alcohol abuse.
• History of lactic acidosis during metformin therapy.
• Active peptic ulcer.
• Congenital adrenal hyperplasia.
• Cushing's syndrome.
• Androgen secreting neoplasia.
• Patients who were using spironolactone, other anti-androgens, or any form of hormone therapy for the treatment of hirsutism at least 3 months before enrollment in the study.
• Decompensated heart failure.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Kasr El-Ainy hospital

Cairo, Egypt

RECRUITING

Related Publications (19)

• Tiganis T. Reactive oxygen species and insulin resistance: the good, the bad and the ugly. Trends Pharmacol Sci. 2011 Feb;32(2):82-9. doi: 10.1016/j.tips.2010.11.006. Epub 2010 Dec 14.

  PMID: 21159388 BACKGROUND

• Pei Y, Liu H, Yang Y, Yang Y, Jiao Y, Tay FR, Chen J. Biological Activities and Potential Oral Applications of N-Acetylcysteine: Progress and Prospects. Oxid Med Cell Longev. 2018 Apr 22;2018:2835787. doi: 10.1155/2018/2835787. eCollection 2018.

  PMID: 29849877 BACKGROUND

• Yifu P. A review of antioxidant N-acetylcysteine in addressing polycystic ovary syndrome. Gynecol Endocrinol. 2024 Dec;40(1):2381498. doi: 10.1080/09513590.2024.2381498. Epub 2024 Jul 22.

  PMID: 39039898 BACKGROUND

• Christ JP, Cedars MI. Current Guidelines for Diagnosing PCOS. Diagnostics (Basel). 2023 Mar 15;13(6):1113. doi: 10.3390/diagnostics13061113.

  PMID: 36980421 BACKGROUND

• Gayatri K, Kumar JS, and Kumar BB. Metformin and N-acetyl cysteine in polycystic ovarian syndrome--a comparative study. Indian Journal of Clinical Medicine. 2023;15;24(18):14126. doi.org/10.1177/117739361000100002

  BACKGROUND

• Scholze A, Rinder C, Beige J, Riezler R, Zidek W, Tepel M. Acetylcysteine reduces plasma homocysteine concentration and improves pulse pressure and endothelial function in patients with end-stage renal failure. Circulation. 2004 Jan 27;109(3):369-74. doi: 10.1161/01.CIR.0000109492.65802.AD. Epub 2004 Jan 19.

  PMID: 14732754 BACKGROUND

• Fulghesu AM, Ciampelli M, Muzj G, Belosi C, Selvaggi L, Ayala GF, Lanzone A. N-acetyl-cysteine treatment improves insulin sensitivity in women with polycystic ovary syndrome. Fertil Steril. 2002 Jun;77(6):1128-35. doi: 10.1016/s0015-0282(02)03133-3.

  PMID: 12057717 BACKGROUND

• De Mattia G, Bravi MC, Laurenti O, Cassone-Faldetta M, Proietti A, De Luca O, Armiento A, Ferri C. Reduction of oxidative stress by oral N-acetyl-L-cysteine treatment decreases plasma soluble vascular cell adhesion molecule-1 concentrations in non-obese, non-dyslipidaemic, normotensive, patients with non-insulin-dependent diabetes. Diabetologia. 1998 Nov;41(11):1392-6. doi: 10.1007/s001250051082.

  PMID: 9833950 BACKGROUND

• Brown J, Farquhar C. Clomiphene and other antioestrogens for ovulation induction in polycystic ovarian syndrome. Cochrane Database Syst Rev. 2016 Dec 15;12(12):CD002249. doi: 10.1002/14651858.CD002249.pub5.

  PMID: 27976369 BACKGROUND

• Costello M, Garad R, Hart R, Homer H, Johnson L, Jordan C, Mocanu E, Qiao J, Rombauts L, Teede HJ, Vanky E, Venetis C, Ledger W. A Review of First Line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome. Med Sci (Basel). 2019 Sep 10;7(9):95. doi: 10.3390/medsci7090095.

  PMID: 31510088 BACKGROUND

• Martin KA, Anderson RR, Chang RJ, Ehrmann DA, Lobo RA, Murad MH, Pugeat MM, Rosenfield RL. Evaluation and Treatment of Hirsutism in Premenopausal Women: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2018 Apr 1;103(4):1233-1257. doi: 10.1210/jc.2018-00241.

  PMID: 29522147 BACKGROUND

• Greff D, Juhasz AE, Vancsa S, Varadi A, Sipos Z, Szinte J, Park S, Hegyi P, Nyirady P, Acs N, Varbiro S, Horvath EM. Inositol is an effective and safe treatment in polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials. Reprod Biol Endocrinol. 2023 Jan 26;21(1):10. doi: 10.1186/s12958-023-01055-z.

  PMID: 36703143 BACKGROUND

• Teede HJ, Misso ML, Costello MF, Dokras A, Laven J, Moran L, Piltonen T, Norman RJ; International PCOS Network. Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome. Fertil Steril. 2018 Aug;110(3):364-379. doi: 10.1016/j.fertnstert.2018.05.004. Epub 2018 Jul 19.

  PMID: 30033227 BACKGROUND

• Dason ES, Koshkina O, Chan C, Sobel M. Diagnosis and management of polycystic ovarian syndrome. CMAJ. 2024 Jan 28;196(3):E85-E94. doi: 10.1503/cmaj.231251. No abstract available.

  PMID: 38286488 BACKGROUND

• Schuring AN, Schulte N, Sonntag B, Kiesel L. Androgens and insulin--two key players in polycystic ovary syndrome. Recent concepts in the pathophysiology and genetics of polycystic ovary syndrome. Gynakol Geburtshilfliche Rundsch. 2008;48(1):9-15. doi: 10.1159/000111465. Epub 2008 Jan 17.

  PMID: 18209494 BACKGROUND

• Zeber-Lubecka N, Ciebiera M, Hennig EE. Polycystic Ovary Syndrome and Oxidative Stress-From Bench to Bedside. Int J Mol Sci. 2023 Sep 15;24(18):14126. doi: 10.3390/ijms241814126.

  PMID: 37762427 BACKGROUND

• International Evidence-Based Guideline for the Assessment. 2023, www.monash.edu/__data/assets/pdf_file/0003/3379521/Evidence-Based-Guidelines-2023.pdf.

  BACKGROUND

• Rotterdam ESHRE/ASRM-Sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004 Jan;19(1):41-7. doi: 10.1093/humrep/deh098.

  PMID: 14688154 BACKGROUND

• Skiba MA, Islam RM, Bell RJ, Davis SR. Understanding variation in prevalence estimates of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2018 Nov 1;24(6):694-709. doi: 10.1093/humupd/dmy022.

  PMID: 30059968 BACKGROUND

Related Links

• Polycystic Ovary Syndrome and Oxidative Stress-From Bench to Bedside

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

Acetylcysteine

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

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Samar F Farid, PhD

  Professor and Head of Clinical Pharmacy Department, Faculty of Pharmacy, Cairo University

  STUDY DIRECTOR

• Eglal A Mostafa Bassiouny, PhD

  Lecturer of Clinical Pharmacy Faculty of Pharmacy, Cairo University

  STUDY DIRECTOR

• Amr Z Abdelhamid, PhD

  Obstetrics and Gynaecology Lecturer Kasr Al-Ainy School of Medicine, Cairo University

  STUDY DIRECTOR

Central Study Contacts

Marwa R Talat, BPharm

CONTACT

+201069342847; marwa.rafat@pharma.cu.edu.eg

Eglal A Mostafa Bassiouny, PhD

CONTACT

+201061500242; eglal.mostafa@pharma.cu.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Demonstrator and Teaching assistant

Model Details: A prospective, randomized, interventional, open-label controlled parallel design study

Study Record Dates

• First Submitted: January 30, 2025
• First Posted: February 20, 2025
• Study Start: March 1, 2025
• Primary Completion: February 1, 2026
• Study Completion: May 1, 2026
• Last Updated: July 9, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)