PCOS Treatment Using DLBS3233, Metformin, and Combination of Both

Insulin Resistance Clinical Trial

— POSITIF  

Official title:

Polycystic Ovary Syndrome Treatment Using DLBS3233, Metformin, and Combination of Both, and Its Relation to Fertility

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01999686
• Other study ID #: DLBS3233-1013
• Status: Completed
• Phase: Phase 3
• Start date: October 2014
• Est. completion date: May 2019

Study information

• Verified date: May 2019
• Source: Dexa Medica Group
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a 3-arm, randomized, double-blind, double-dummy, and controlled clinical study over 6 months of treatment to evaluate the metabolic and clinical efficacy as well as the safety of DLBS3233 alone, metformin and combination of both, in improving metabolic and reproductive parameters.

Description:

There will be 3 groups of treatment (N = 186), each consist of 62 subjects, as the following:

• Treatment I : DLBS3233 100 mg once daily

• Treatment II : Metformin XR 750 mg twice daily

• Treatment III : DLBS3233 100 mg once daily and Metformin XR 750 mg twice daily.

Laboratory examination to evaluate metabolic efficacy parameters will be performed at baseline, Month 3rd, and end of study (Month 6th).

Clinical and laboratory examination to evaluate the reproductive efficacy parameters using trans-vaginal USG and biomarkers (such as reproductive hormones) will be performed at baseline to the end of study.

Safety examination will be performed at baseline and end of study. Occurrence of adverse event will be observed along the study conduct.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 186
• Est. completion date: May 2019
• Est. primary completion date: February 2019
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

1. Signed written informed consent prior to participation in the study.

2. Female subjects in reproductive age (i.e. 18-40 years) willing to conceive.

3. Subject with a diagnosis of polycystic ovary syndrome confirmed by two of the following (Rotterdam Criteria):

• Hyperandrogenism (defined by elevated free testosterone concentration; or Ferriman-Gallwey Score of = 8).

• Ovarian dysfunction indicated by menstrual irregularity: oligomenorrhea (cycles of > 35 days), or amenorrhea (no menses in the last of 3 months) after negative screening pregnancy test.

• Polycystic ovary as shown by ultrasonography (USG).

4. Subject with insulin resistance defined by : HOMA-IR of > 2.00.

5. Subject with body mass index (BMI) of 19-35 inclusive.

6. Able to take oral medication.

Exclusion Criteria:

1. Pregnant or lactating women (urinary pregnancy test will be applied at screening).

2. Based on previous or current medical (either laboratory or clinical) examination, subjects known to have any of the following conditions:

• Cushing's syndrome, late onset of congenital adrenal hyperplasia, androgen-secreting tumors, uncontrolled thyroid disease, hyperprolactinemia.

3. Known to have the following medical condition:

• Diabetes mellitus,

• Uncontrolled hypertension

• Symptomatic cardiovascular diseases:

• Acute or chronic infections at baseline.

• Any known malignancies.

4. History of gynecological surgery.

5. Impaired renal function

6. Impaired liver function

7. Medically-assisted weight loss with medications or surgical procedures.

8. Currently having laparoscopic ovarian diathermy (LOD).

9. Currently under treatment with in vitro fertilization (IVF) techniques.

10. Have been regularly taking any of the following medications, within = 3 months prior to screening, such as:

• Clomiphene citrate

• Insulin sensitizers, i.e. metformin and thiazolidinediones

• Aromatase inhibitors, such as: anastrozole, letrozole

• Glucocorticoids

• Gonadotropins

• Gonadotropin-releasing hormone agonists (GnRHa)

• Oral contraceptive pills (OCPs)

• Antiandrogens, such as: spironolactone, cyproterone acetate (CPA), and flutamide

• Any traditional or herbal medicines

11. Participating in other clinical trial within 30 days prior to screening.

Related Conditions & MeSH terms

• Insulin Resistance
• Polycystic Ovary Syndrome
• Polycystic Ovary Syndrome (PCOS)
• Syndrome

Intervention

Drug:
• DLBS3233

• Metformin XR

• Placebo metformin
Placebo metformin has the same ingredients with Metformin XR caplet, except that it does not contain the active substance (metformin).
• Placebo DLBS3233
Placebo DLBS3233 has the same ingredients with DLBS3233 capsule, except that it does not contain the active substance (DLBS3233).

Locations

Country	Name	City	State
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lambung Mangkurat, Ulin Banjarmasin Hospital	Banjarmasin
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Udayana, Sanglah Hospital	Denpasar
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Hasanuddin, Dr. Wahidin Sudirohusodo Hospital	Makasar
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Brawijaya, Dr. Saiful Anwar Hospital	Malang
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. Kandou Hospital	Manado
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital	Semarang
Indonesia	Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Airlangga, Dr. Soetomo Hospital.	Surabaya

Sponsors (1)

Lead Sponsor	Collaborator
Dexa Medica Group

Country where clinical trial is conducted

Indonesia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HOMA-IR reduction	HOMA-IR reduction from baseline to Month 6th (end of study)	6 months
Secondary	Lipid profile improvement	Lipid profile improvement (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides level) from baseline to Month 3rd and Month 6th (end of study)	3 and 6 months
Secondary	Improvement of glucose tolerance	Improvement of glucose tolerance (reduction of FPG and 2-hour PPPG) from baseline to Month 3rd and Month 6th (end of study)	3 and 6 months
Secondary	Change of waist circumference	1, 2, 3, 4, 5, and 6 months	1, 2, 3, 4, 5, and 6 months
Secondary	Response rate: presence of ovulation	Presence of ovulation will be evaluated using trans-vaginal USG to find dominant follicle(s), at the day/period of ovulation, starting from menstrual cycle of Month 3rd up to Month 6th. Measurement of progesterone level will be performed 7 days after the finding of dominant follicle on USG examination to confirm the presence of ovulation.	menstrual cycle of Month 3rd up to that of Month 6th
Secondary	Change of endometrium thickness	Change of endometrium thickness will be measured by using trans-vaginal USG at basal condition and at the day/period of ovulation	3 to 6 months
Secondary	Improvement of S/A ratio	Improvement from baseline of the S/A ratio (defined as the ratio between stromal and total area of median ovarian section) will be measured using trans-vaginal USG (trans-longitudinal measurement) at Baseline, menstrual cycle of Month 3rd, and menstrual cycle of Month 6th at basal condition.	3 to 6 months
Secondary	Improvement in Ferriman-Gallwey Score	Improvement in Ferriman-Gallwey Score from baseline to Month 3rd and Month 6th (the end of study)	3 and 6 months
Secondary	Reduction of free testosterone level	Reduction of free testosterone level from baseline to Month 6th (end of study)	6 months
Secondary	Change of luteinizing hormone (LH) level	Change of luteinizing hormone (LH) level from baseline to Month 6th (end of study)	6 months
Secondary	Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio	Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio from baseline to Month 6th (end of study)	6 months
Secondary	Liver function	Liver function (levels of serum AST, ALT, alkaline phosphatase) will be measured at baseline and Month 6th (end of study)	6 months
Secondary	Renal function	Renal function (levels of serum creatinine, BUN) will be measured at baseline and Month 6th (end of study)	6 months
Secondary	Number of adverse events and subjects with events	Adverse events as well as number of events and subjects experiencing the events will be observed and evaluated throughout study period (6 months) and until all adverse events have been recovered or stabilized	During 6 months