Effects of Metformin and Theory-Based Education in Women With Polycystic Ovary Syndrome

NCT07811856 | Completed Phase 4

• 1 other identifier: PCOS-MET-EDU-2025-01
• Study Type: interventional
• Target: 900
• Locations: 1 country
• Sites: 1

Brief Summary

Polycystic ovary syndrome (PCOS) is a common condition associated with metabolic abnormalities, including insulin resistance, impaired glucose regulation, and abnormal lipid levels. Metformin is commonly used to improve metabolic outcomes in women with PCOS, while lifestyle modification and behavioral education are important components of PCOS management. This study evaluates whether metformin, alone or combined with a theory-based behavioral educational program, is associated with changes in metabolic, vitamin B12, iron-status, erythropoietin, and hematological parameters compared with matching placebo. This is a prospective, three-arm, parallel-group randomized controlled trial conducted among women aged 18-40 years with specialist-confirmed PCOS in Ministry of Health obstetrics and gynecology clinics in Jordan. A total of 900 participants were initially randomized in a 1:1:1 ratio to receive matching placebo, metformin, or metformin combined with a theory-based behavioral educational program. The metformin groups received 1500 mg/day, administered as 500 mg three times daily, for six months. The combined intervention group additionally received five structured educational sessions addressing PCOS self-management, healthy dietary practices, physical activity, weight and waist management, metformin adherence, sleep, stress management, problem solving, and maintenance of healthy behaviors. Clinical and laboratory outcomes were assessed at baseline and after six months. The primary outcomes include changes in anthropometric, metabolic, vitamin B12, iron-status, erythropoietic, and hematological parameters. Changes in PCOS-related knowledge and lifestyle practices were also evaluated among participants receiving the combined intervention.

Conditions

Polycystic Ovary Syndrome (PCOS) Women

Keywords

Metformin; PCOS; heory-Based Behavioral Education; Lifestyle Education; Vitamin B12; Iron Status; Erythropoietin; Metabolic Outcomes; Hematological Parameters

Outcome Measures

Primary Outcomes (24)

• Change in Body Mass Index (BMI) From Baseline to 6 Months

  Change in body mass index (BMI) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Serum Insulin From Baseline to 6 Months

  Change in serum insulin from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in HOMA-IR From Baseline to 6 Months

  Change in homeostasis model assessment of insulin resistance (HOMA-IR) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Total Cholesterol (TC) From Baseline to 6 Months

  Change in total cholesterol (TC) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Triglycerides (TG) From Baseline to 6 Months

  Change in triglycerides (TG) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to 6 Months

  Change in low-density lipoprotein cholesterol (LDL-C) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in High-Density Lipoprotein Cholesterol (HDL-C) From Baseline to 6 Months

  Change in high-density lipoprotein cholesterol (HDL-C) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Serum Vitamin B12 From Baseline to 6 Months

  Change in serum vitamin B12 concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Serum Iron From Baseline to 6 Months

  Change in serum iron concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Serum Ferritin From Baseline to 6 Months

  Change in serum ferritin concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Total Iron-Binding Capacity (TIBC) From Baseline to 6 Months

  Change in total iron-binding capacity (TIBC) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Transferrin Saturation (TSAT) From Baseline to 6 Months

  Change in transferrin saturation (TSAT) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Serum Erythropoietin (EPO) From Baseline to 6 Months

  Change in serum erythropoietin (EPO) concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Hemoglobin (Hb) From Baseline to 6 Months

  Change in hemoglobin (Hb) concentration from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Hematocrit (Hct) From Baseline to 6 Months

  Change in hematocrit (Hct) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Mean Corpuscular Volume (MCV) From Baseline to 6 Months

  Change in mean corpuscular volume (MCV) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Mean Corpuscular Hemoglobin (MCH) From Baseline to 6 Months

  Change in mean corpuscular hemoglobin (MCH) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Mean Corpuscular Hemoglobin Concentration (MCHC) From Baseline to 6 Months

  Change in mean corpuscular hemoglobin concentration (MCHC) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Red Cell Distribution Width (RDW) From Baseline to 6 Months

  Change in red cell distribution width (RDW) from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in White Blood Cell (WBC) Count From Baseline to 6 Months

  Change in neutrophil count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Lymphocyte Count From Baseline to 6 Months

  Change in lymphocyte count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Eosinophil Count From Baseline to 6 Months

  Change in eosinophil count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Basophil Count From Baseline to 6 Months

  Change in basophil count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

• Change in Platelet Count From Baseline to 6 Months

  Change in platelet count from baseline to 6 months among participants assigned to the matching placebo, metformin, or metformin plus theory-based behavioral education groups.

  Baseline to 6 months

Secondary Outcomes (1)

• Change in PCOS-Related Knowledge and Lifestyle Practices From Baseline to 6 Months

  Baseline to 6 months

Study Arms (3)

Matching Placebo Group

ACTIVE COMPARATOR

Participants received routine clinical care together with matching placebo tablets identical to the metformin tablets in appearance, size, and form for six months. They did not receive study-prescribed metformin or the structured theory-based behavioral educational intervention.

Drug: Matching Placebo

Metformin Group

EXPERIMENTAL

Participants received routine clinical care together with metformin at a total daily dose of 1500 mg, administered as 500 mg three times daily, for six months. They did not receive the structured theory-based behavioral educational intervention.

Drug: MetFORMIN

Metformin Plus Theory-Based Behavioral Education

EXPERIMENTAL

Participants received routine clinical care together with metformin at a total daily dose of 1500 mg, administered as 500 mg three times daily, for six months, plus a structured theory-based behavioral educational program. The program consisted of five structured sessions addressing PCOS self-management, healthy dietary practices, physical activity, sedentary behavior, weight and waist management, metformin adherence, metabolic health, sleep, stress management, problem solving, and maintenance of behavioral changes.

Drug: MetFORMIN; Behavioral: Theory-Based Behavioral Educational Program

Interventions

MetFORMIN DRUG

Metformin was administered at a total daily dose of 1500 mg, given as 500 mg three times daily, for six months.

Metformin Group; Metformin Plus Theory-Based Behavioral Education

Matching Placebo DRUG

Matching placebo tablets identical to the metformin tablets in appearance, size, and form were administered for six months.

Matching Placebo Group

Theory-Based Behavioral Educational Program BEHAVIORAL

A structured behavioral educational program grounded in Bandura's Self-Efficacy Theory was provided to participants in the combined intervention group. The program consisted of five structured sessions addressing PCOS self-management, healthy dietary practices, physical activity and sedentary behavior, weight and waist management, metformin adherence, metabolic health, sleep, stress management, problem solving, and maintenance of behavioral changes.

Metformin Plus Theory-Based Behavioral Education

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 18-40 years.
• Specialist-confirmed diagnosis of polycystic ovary syndrome (PCOS).
• Ability and willingness to participate in the six-month study follow-up.
• Ability to comply with the study procedures and assessments.

You may not qualify if:

• Chronic hemolytic anemia.
• Chronic kidney disease.
• Hepatic disorders.
• Other endocrine, metabolic, or cardiovascular conditions that could affect glucose metabolism, vitamin B12 status, iron status, erythropoietin levels, or hematological parameters.
• Previous use of insulin-sensitizing medications other than the study metformin.
• Current or recent hormonal therapy that could affect the study outcomes.
• Current use of iron or vitamin B12 supplements.
• Use of medications that could substantially affect glucose metabolism, vitamin B12 status, iron status, erythropoietin levels, or hematological parameters.
• Any condition that could interfere with adherence to the intervention or completion of the six-month follow-up.

Sponsors & Collaborators

• Jerash Private University: lead

Study Sites (1)

Jerash University

Amman, 009627, Jordan

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

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

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The educational intervention could not be masked because participants were aware of their participation in the behavioral educational program. The pharmacological groups received either metformin or matching placebo tablets. Standardized procedures were used for clinical assessment, laboratory measurements, data collection, and statistical analysis.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor DOCTOR

Model Details: Participants were randomly allocated in a 1:1:1 ratio to three parallel groups: matching placebo, metformin, or metformin combined with a theory-based behavioral educational program. All groups received routine clinical care and were followed for six months.

Study Record Dates

• First Submitted: September 4, 2026
• First Posted: September 10, 2026
• Study Start: August 1, 2026
• Primary Completion: August 1, 2026
• Study Completion: August 1, 2026
• Last Updated: September 10, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

JO (1)