Efficacy of Canagliflozin Versus Metformin in Women With Polycystic Ovary Syndrome

NCT06256289 | Not Yet Recruiting Phase 4

• 1 other identifier: FirstofShanxiMU
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this clinical trial is to investigate the use of ultra-high performance liquid chromatography-mass spectrometry for metabolomics and proteomics research in patients with Polycystic Ovary Syndrome (PCOS) and Non-Alcoholic Fatty Liver Disease (NAFLD). The main questions it aims to answer are:

• How can this technology help identify specific biomarkers for diagnosing PCOS combined with NAFLD?
• What is the role of Canagliflozin in improving the safety and efficacy of treatment for PCOS and NAFLD patients? Participants, who are 50 non-diabetic women with PCOS, will undergo a series of assessments including cardiovascular metabolic indicators, liver NAFLD screening risk stratification, and insulin resistance index. They will be compared with 50 age and BMI-matched healthy controls. The participants will be randomized to receive either CANA/MET (Canagliflozin 100 mg daily plus Metformin 1000 mg twice daily) or MET (Metformin 1000 mg twice daily) for a continuous period of three months. The study will evaluate various parameters including menstrual patterns, anthropometric parameters, gonadal parameters, glucose-lipid homeostasis, liver enzyme indices, non-invasive hepatic fat changes, metabolomics, and NAFLD-related indicators.

Conditions

Polycystic Ovary Syndrome; Non-Alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• liver steatosis index CAP (Controlled Attenuation Parameter) measured by FibroScan

  Changes in the liver steatosis index CAP (Controlled Attenuation Parameter) as measured by transient elastography after 12 weeks of treatment.

  at baseline and 12 weeks

Secondary Outcomes (6)

• liver stiffness index (LS） measured by transient elastography, FibroScan

  at baseline and 12 weeks

• Body Composition, including total body water, muscle mass, fat mass (subcutaneous and visceral), fat-free mass detected using Bioelectrical Impedance Analysis (BIA)

  at baseline and 12 weeks

• selection of proteomics markers using liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry for analysis

  at baseline and 12 weeks

• selection of metabolomics markers by by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometryprecision

  at baseline and 12 weeks

• sex hormones by liquid chromatography-tandem mass spectrometry (LC-MS/MS) mass spectrometry

  at baseline and after 12 weeks

Study Arms (2)

canagliflozin plus metformin group

EXPERIMENTAL

canagliflozin 100 mg once daily plus metformin 1000 mg twice daily

Drug: Canagliflozin 100mg Tab; Drug: Metformin Hydrochloride

metformin group

ACTIVE COMPARATOR

metformin 1000 mg twice daily

Drug: Metformin Hydrochloride

Interventions

Canagliflozin 100mg Tab DRUG

Canagliflozin 100mg once daily combined Metformin 1000mg twice daily

Also known as: Invokana

canagliflozin plus metformin group

Metformin Hydrochloride DRUG

Metformin 1000mg twice daily

Also known as: Glucophage

canagliflozin plus metformin group; metformin group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• aged 18-45 years old;
• Body mass index (BMI) more than 18.5 kg / m2;
• PCOS diagnosis meets Rotterdam 2003 criteria: at least two of the following symptoms: menstrual menstruation / amenorrhea, hyperandrogenism, and / or biochemical and / or clinical signs of polycystic ovaries.
• The serum pregnancy test was negative before enrollment.
• Clinical diagnosis of fatty liver: the ratio of liver to kidney is greater than 1.0.
• Can understand the procedures and methods of this clinical trial, patients voluntarily participate and sign the informed consent form, willing to comply with the trial protocol requirements and cooperate with the provision of biological samples for testing as planned.

You may not qualify if:

• Less than 18 years old or more than 45 years old;
• Patients who are pregnant, intend to become pregnant, are breastfeeding or giving birth;
• Drug history in the past three months included oral contraceptives, sodium-dependent glucose transporters 2 inhibitors, glucagon-like peptide-1 receptor agonists, thiazolidinediones, metformin, corticosteroids or traditional Chinese medicine.
• Endocrine disorders such as hyperprolactinemia, thyroid dysfunction and diabetes, Cushing's syndrome, 21-hydroxylase deficiency, congenital adrenal hyperplasia, androgen-secreting tumors, cervical, endometrial or breast cancer.
• Severe liver function (alanine aminase, aspartate aminase\> 3 times normal value or elevation of serum bilirubin to more than 3 times the upper limit of normal) or renal impairment (eGFR \<60 ml/min/1.73m2).Severe cardiopulmonary, hematopoietic and hematopoietic insufficiency.
• Current or past (most recent three months) participation in other studies.
• Viral hepatitis, autoimmune hepatitis, primary biliary cirrhosis, sclerosing cholangitis, hemochromatosis, anti-trypsin defense, Wilson disease, parenteral nutrition history, use of drugs known to cause steatosis (such as valproate, amiodarone or vitamin E) or liver injury caused by drug abuse.Clinical evidence of hepatic decompensation, such as hepatic encephalopathy, ascites, and variceal bleeding.
• drank more than 20g per day.
• Women with persistent or recurrent symptomatic urinary tract infections (UTI), gastrointestinal (GI) problems, or any other condition that may compromise patient safety had strong fertility needs within six months of the study period.
• Allergic or intolerant to the study drug, unable to continue treatment as required by the protocol, unwilling to complete the study or become pregnant.
• History of mental illness within 2 years, including any suicidal behavior or major depression, depressive symptoms (defined as Patient Health Questionnaire-9 score more than 15), central nervous system disease (including but not limited to any type of seizure or stroke), and no cognitive behavior (including the investigator considers poor adherence to evaluate efficacy or is unlikely to complete the intended course and follow-up).

Sponsors & Collaborators

• Ping Li,MD: lead

Related Publications (13)

• Rocha ALL, Faria LC, Guimaraes TCM, Moreira GV, Candido AL, Couto CA, Reis FM. Non-alcoholic fatty liver disease in women with polycystic ovary syndrome: systematic review and meta-analysis. J Endocrinol Invest. 2017 Dec;40(12):1279-1288. doi: 10.1007/s40618-017-0708-9. Epub 2017 Jun 13.

  PMID: 28612285 BACKGROUND

• Makri E, Tziomalos K. Prevalence, etiology and management of non-alcoholic fatty liver disease in patients with polycystic ovary syndrome. Minerva Endocrinol. 2017 Jun;42(2):122-131. doi: 10.23736/S0391-1977.16.02564-5. Epub 2016 Oct 28.

  PMID: 27792214 BACKGROUND

• De Sousa SM Dr, Norman RJ Prof. Metabolic syndrome, diet and exercise. Best Pract Res Clin Obstet Gynaecol. 2016 Nov;37:140-151. doi: 10.1016/j.bpobgyn.2016.01.006. Epub 2016 Feb 10.

  PMID: 26972165 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. Fertil Steril. 2004 Jan;81(1):19-25. doi: 10.1016/j.fertnstert.2003.10.004.

  PMID: 14711538 BACKGROUND

• Macut D, Tziomalos K, Bozic-Antic I, Bjekic-Macut J, Katsikis I, Papadakis E, Andric Z, Panidis D. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Hum Reprod. 2016 Jun;31(6):1347-53. doi: 10.1093/humrep/dew076. Epub 2016 Apr 12.

  PMID: 27076501 BACKGROUND

• March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod. 2010 Feb;25(2):544-51. doi: 10.1093/humrep/dep399. Epub 2009 Nov 12.

  PMID: 19910321 BACKGROUND

• Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, Janssen OE, Legro RS, Norman RJ, Taylor AE, Witchel SF; Androgen Excess Society. Positions statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab. 2006 Nov;91(11):4237-45. doi: 10.1210/jc.2006-0178. Epub 2006 Aug 29.

  PMID: 16940456 BACKGROUND

• Teede HJ, Hutchison SK, Zoungas S. The management of insulin resistance in polycystic ovary syndrome. Trends Endocrinol Metab. 2007 Sep;18(7):273-9. doi: 10.1016/j.tem.2007.08.001. Epub 2007 Aug 16.

  PMID: 17698366 BACKGROUND

• Meyer C, McGrath BP, Teede HJ. Overweight women with polycystic ovary syndrome have evidence of subclinical cardiovascular disease. J Clin Endocrinol Metab. 2005 Oct;90(10):5711-6. doi: 10.1210/jc.2005-0011. Epub 2005 Jul 26.

  PMID: 16046590 BACKGROUND

• Wild RA, Painter PC, Coulson PB, Carruth KB, Ranney GB. Lipoprotein lipid concentrations and cardiovascular risk in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 1985 Nov;61(5):946-51. doi: 10.1210/jcem-61-5-946.

  PMID: 4044782 BACKGROUND

• Mantovani A, Byrne CD, Scorletti E, Mantzoros CS, Targher G. Efficacy and safety of anti-hyperglycaemic drugs in patients with non-alcoholic fatty liver disease with or without diabetes: An updated systematic review of randomized controlled trials. Diabetes Metab. 2020 Nov;46(6):427-441. doi: 10.1016/j.diabet.2019.12.007. Epub 2020 Jan 7.

  PMID: 31923578 BACKGROUND

• Itani T, Ishihara T. Efficacy of canagliflozin against nonalcoholic fatty liver disease: a prospective cohort study. Obes Sci Pract. 2018 Aug 22;4(5):477-482. doi: 10.1002/osp4.294. eCollection 2018 Oct.

  PMID: 30338118 BACKGROUND

• Cai M, Shao X, Xing F, Zhang Y, Gao X, Zeng Q, Dilimulati D, Qu S, Zhang M. Efficacy of canagliflozin versus metformin in women with polycystic ovary syndrome: A randomized, open-label, noninferiority trial. Diabetes Obes Metab. 2022 Feb;24(2):312-320. doi: 10.1111/dom.14583. Epub 2021 Nov 25.

  PMID: 34726324 BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Non-alcoholic Fatty Liver Disease

Interventions

Canagliflozin; 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; Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates; Biguanides; Guanidines; Amidines

Study Officials

• Ping Li, MD

  The First Affiliated Hospital of Shanxi Medical University

  STUDY CHAIR

• Linxin Xu, MD

  The First Affiliated Hospital of Shanxi Medical University

  PRINCIPAL INVESTIGATOR

• Yan Wang

  The First Affiliated Hospital of Shanxi Medical University

  STUDY DIRECTOR

Central Study Contacts

Ping Li, MD

CONTACT

15296791363; lp06010319@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: January 28, 2024
• First Posted: February 13, 2024
• Study Start: March 31, 2024
• Primary Completion: April 30, 2025
• Study Completion: April 30, 2025
• Last Updated: February 13, 2024

Record last verified: 2024-02