Clinical trial NCT01999686: PCOS Treatment Using DLBS3233, Metformin, and Combination of Both
Official title: Polycystic Ovary Syndrome Treatment Using DLBS3233, Metformin, and Combination of Both, and Its Relation to Fertility
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycystic Ovary Syndrome (PCOS)
Insulin Resistance
Keywords: Polycystic ovarium syndrome
DLBS3233
metformin
insulin resistance
Female
Lead sponsor: Dexa Medica Group
Sponsor class: INDUSTRY
First posted: 2013-12-03
Enrollment: 186
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: HOMA-IR reduction
timeFrame: 6 months
Secondary outcomes:
measure: Lipid profile improvement
timeFrame: 3 and 6 months
measure: Improvement of glucose tolerance
timeFrame: 3 and 6 months
measure: Change of waist circumference
timeFrame: 1, 2, 3, 4, 5, and 6 months
measure: Response rate: presence of ovulation
timeFrame: menstrual cycle of Month 3rd up to that of Month 6th
measure: Change of endometrium thickness
timeFrame: 3 to 6 months
measure: Improvement of S/A ratio
timeFrame: 3 to 6 months
measure: Improvement in Ferriman-Gallwey Score
timeFrame: 3 and 6 months
measure: Reduction of free testosterone level
timeFrame: 6 months
measure: Change of luteinizing hormone (LH) level
timeFrame: 6 months
measure: Change of luteinizing hormone (LH) / follicle stimulating hormone (FSH) ratio
timeFrame: 6 months
measure: Liver function
timeFrame: 6 months
measure: Renal function
timeFrame: 6 months
measure: Number of adverse events and subjects with events
timeFrame: During 6 months
Other outcomes:
Locations:
city: Banjarmasin
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lambung Mangkurat, Ulin Banjarmasin Hospital
city: Denpasar
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Udayana, Sanglah Hospital
city: Makasar
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Hasanuddin, Dr. Wahidin Sudirohusodo Hospital
city: Malang
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Brawijaya, Dr. Saiful Anwar Hospital
city: Manado
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. Kandou Hospital
city: Semarang
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital
city: Surabaya
country: Indonesia
facility: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Airlangga, Dr. Soetomo Hospital.
Study officials:
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Airlangga, Dr. Soetomo Hospital, Surabaya, Indonesia.
name: Soehartono Ds, Prof. dr., SpOG-K
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Brawijaya, Dr. Saiful Anwar Hospital, Malang, Indonesia.
name: Arsana Wiyasa IW, Dr. dr., SpOG-K
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Udayana, Sanglah Hospital, Denpasar, Indonesia.
name: Putu Doster Mahayasa, dr., SpOG-K
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia.
name: Syarief Taufik, dr., SpOG-K
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Hasanuddin, Dr. Wahidin Sudirohusodo Hospital, Makasar, Indonesia.
name: Nusratuddin Abdullah, Dr. dr., SpOG-K, MARS
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lambung Mangkurat, Ulin Banjarmasin Hospital, Banjarmasin, Indonesia.
name: Iwan Darma Putra, dr., SpOG-K
role: PRINCIPAL_INVESTIGATOR
affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Faculty of Medicine, University of Sam Ratulangi, Prof. Dr. Kandou Hospital, Manado, Indonesia.
name: Eddy Suparman, Prof. Dr. dr., SpOG-K
role: PRINCIPAL_INVESTIGATOR
References: