Amelioration of Polycystic Ovary Syndrome Related Disorders by Supplementation of Thymoquinone and Metformin

NCT04852510 | Completed Phase 2

• 1 other identifier: SGHM-JAN2019-OBGYN
• Study Type: interventional
• Target: 253
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: To investigate the potential benefit of adding Thymoquinone to Metformin in alleviating symptoms of polycystic ovarian syndrome. Methods: 207 overweight and obese PCOS Patients were divided into two groups. Patients in Group A, received Metformin 500 mg three times daily for 6 months. Patients in Group B, received a combination of Metformin 500 mg and Thymoquinone in the form of Black Cumin oil 500 mg capsules three times daily for 6 months. Follow up was done after 3 and 6 months from the beginning of the study for evaluation of menstrual cycle pattern, body mass index, Waist circumference, Hip circumference, and Waist / Hip ratio, Oral glucose tolerance test, Glycosylated Hemoglobin A1C, Superoxide dismutase activity and Malondialdehyde concentration.

Conditions

Polycystic Ovary Syndrome (PCOS)

Outcome Measures

Primary Outcomes (7)

• The change of menstrual cycle pattern.

  Patients were asked about their menstrual cycle pattern (Frequency of menstrual cycles and number of days of menses). Resumption of normal menstrual cyclicity was defined as having menses every 3-5 weeks. Amenorrhea was defined as absence of menstruation for six or more months. Oligomenorrhea was defined as cycle interval of more than 35 days but less than 6 months.

  At the beginning of the study, After 3 months and After 6 Months

• The change of body mass index (BMI).

  The body mass index is calculated as the body weight in kilograms divided by the height in meters squared. Normal BMI was defined as a range of 18.5-24.9 kg/m2. Overweight defined as body mass index (BMI) 25-29.9 kg/m2 and obesity defined as BMI ≥ 30 kg/m2.

  At the beginning of the study, After 3 months and After 6 Months

• Change of body fat distribution as proved by change of Waist/Hip ratio.

  Waist circumference was measured at the midpoint between the lower margin of the last palpable rib and the top of the iliac crest. Hip circumference was measured around the widest portion of the buttocks. For both measurements, the tape was adjusted parallel to the floor at the level at which the measurement was made. The tape was held snugly around the body, but not pulled so tight. The patient was standing with feet close together, arms at the sides and body weight evenly distributed across the feet. The waist circumference was measured at the end of a normal expiration, when the lungs are at their functional residual capacity. Each measurement was repeated twice; if the measurements were within 1 cm of one another, the average was calculated. If the difference between the two measurements exceeded 1 cm, the two measurements were repeated.

  At the beginning of the study, After 3 months and After 6 Months

• Change of oral glucose tolerance test (OGTT) results.

  The oral glucose tolerance test (OGTT) was performed in the morning after an overnight fasting of at least 8 hours, utilizing a glucose load containing the equivalent of 75 grams of anhydrous glucose dissolved in water. Prediabetes was defined by the American Diabetes Association 2014 as those patients who have; impaired fasting glucose (IFG) defined as fasting plasma glucose (FPG) levels of 100 to 125 mg/dL (Fasting was described as no caloric intake for at least 8 hours), or impaired glucose tolerance (IGT) defined as 2-hour readings of 140 to 199 mg/dL in the oral glucose tolerance test (OGTT). Diabetes mellitus was defined According to the American Diabetes Association 2014, as FPG ≥ 126 mg/dL or 2-hour plasma glucose readings ≥ 200 mg/dL during 75 g OGTT.

  At the beginning of the study, After 3 months and After 6 Months

• Change of Glycosylated Hemoglobin A1C levels.

  Glycosylated Hemoglobin A1C levels were measured as percentage (%) from the total hemoglobin. Normal range defined as readings below 5.7%. Prediabetes was defined by the American Diabetes Association 2014 as patients who have their Glycosylated Hemoglobin A1C levels between 5.7% and 6.4%. Diabetes mellitus was defined According to the American Diabetes Association 2014, as Glycosylated Hemoglobin A1C levels ≥ 6.5%.

  At the beginning of the study, After 3 months and After 6 Months

• Change of serum Malondialdehyde (MDA) concentrations.

  Malondialdehyde (MDA) concentrations were measured in µmol/liter using the derivatization MDA with thiobarbituric acid (TBA) based on spectrophotometric determination of pink fluorescent MDA-TBA complex produced after reaction with 2-thiobarbituric acid at high temperature and low pH. The assay kits for MDA and SOD were products of (Cell Biolabs Inc, San Diego, USA).

  At the beginning of the study, After 3 months and After 6 Months

• Change of serum superoxide dismutase (SOD) activity.

  For estimation of SOD activity, centrifugation of the blood samples was done at 1000 g for 10 minutes, the serum was frozen and stored at -80 °C until the time of analysis. SOD activity was based on the ability of the enzyme to inhibit the reduction of nitro blue tetrazolium dye mediated by phenazine methosulphate. The purified SOD inhibits the initial rate of reduction of (O2 to O2-) mediated by the activated phenazine methosulphate which then reduces the nitro blue tetrazolium. The percentage of inhibition was then calculated and compared to the standard of 0.5 μg of the enzyme that produced inhibition of 80 % (activity = 3.000 units/mg protein). The SOD activity was finally expressed as units of enzymatic activity per mg of protein contained in the samples (U/mg protein).

  At the beginning of the study, After 3 months and After 6 Months

Study Arms (2)

Group A

ACTIVE COMPARATOR

Metformin 500 mg three times daily (5) with meals for 6 months (Metfor® 500 mg, Metformin hydrochloride tablets. TABUK Pharmaceutical. KSA).

Drug: Metformin Versus a combination of Metformin and Thymoquinone (TQ)

Group B

ACTIVE COMPARATOR

A combination of Metformin 500 mg three times daily with meals (Metfor® 500 mg, Metformin hydrochloride tablets. TABUK Pharmaceutical. KSA) and Thymoquinone (TQ) in the form of Black Cumin oil (Cumin Mar® Black cumin oil 500 mg soft gel capsules, MARNYS. Spain) three times daily before meals for 6 months.

Drug: Metformin Versus a combination of Metformin and Thymoquinone (TQ)

Interventions

Metformin Versus a combination of Metformin and Thymoquinone (TQ) DRUG

Patients were divided into two groups (A and B) using a computer-based software Open Epi version 3.21. Patients in Group A, received Metformin 500 mg three times daily (5) with meals for 6 months (Metfor® 500 mg, Metformin hydrochloride tablets. TABUK Pharmaceutical. KSA). Patients in Group B, received a combination of Metformin 500 mg three times daily with meals (Metfor® 500 mg, Metformin hydrochloride tablets. TABUK Pharmaceutical. KSA) and Thymoquinone (TQ) in the form of Black Cumin oil (Cumin Mar® Black cumin oil 500 mg soft gel capsules, MARNYS. Spain) three times daily before meals for 6 months.

Also known as: Metfor® 500 mg, Metformin hydrochloride tablets. TABUK Pharmaceutical. KSA, Cumin Mar® Black cumin oil 500 mg soft gel capsules, MARNYS. Spain

Group A; Group B

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Age of 18 to 35 years
• Overweight and obese PCOS patients (overweight defined as body mass index (BMI) 25-29.9 kg/m2 and obesity defined as BMI ≥ 30 kg/m2).
• History of amenorrhea or oligomenorrhea with or without hirsutism. Amenorrhea was defined as absence of menstruation for six or more months. Oligomenorrhea was defined as cycle interval of more than 35 days but less than 6 months.
• PCOS diagnosed according to the 2004 Rotterdam ESHRE/ASRM Consensus workshop, with presence of at least 2 out of 3 criteria: oligo- and/or anovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovarian morphology identified by ultrasound with more than 12 small antral follicles in an ovary.
• Prediabetes defined by the American Diabetes Association 2014, as fasting plasma glucose (FPG) levels of 100 to 125 mg/, or impaired glucose tolerance (IGT) defined as 2-hour readings of 140 to 199 mg/dL in the oral glucose tolerance test (OGTT). Also, patients who had their Glycosylated Hemoglobin A1C levels between 5.7% and 6.4%.

You may not qualify if:

• Lean or average weight PCOS with BMI \< 25 kg/m2, morbidly obese patients with BMI ≥ 35 kg/m2.
• Patients suffering from any other metabolic disorders.
• History of receiving any hormonal treatment or any drug affecting carbohydrate metabolism 3 months prior to the beginning of the study.
• Inability to attend the regular follow up visits.
• Already known and recently diagnosed diabetic patients. According to the American Diabetes Association 2014 (16), diabetes mellitus was defined as Glycosylated Hemoglobin A1C levels ≥ 6.5% or FPG ≥ 126 mg/dL or 2-hour plasma glucose readings ≥ 200 mg/dL during 75 g OGTT, or presence of classic symptoms of hyperglycemia with random plasma glucose levels ≥ 200 mg/dL.
• Thyroid diseases
• Hyperprolactinemia

Sponsors & Collaborators

• Saudi German Hospital - Madinah: lead

Study Sites (1)

Saudi German Hospital

Al Madīnah, Madinah, 41311, Saudi Arabia

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome

Interventions

thymoquinone

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

Study Officials

• Islam Mohamed Magdi Ammar, M.D.

  Saudi German Hospital - Madinah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor and Consultant of Obstetrics and Gynecology

Study Record Dates

• First Submitted: April 9, 2021
• First Posted: April 21, 2021
• Study Start: February 1, 2019
• Primary Completion: August 31, 2020
• Study Completion: August 31, 2020
• Last Updated: April 21, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

SA (1)