Polycystic Ovary SyndromePhase 4NCT01021579
Effects of Metformin Plus Simvastatin on Polycystic Ovarian Syndrome (PCOS): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study
A Phase 4 study testing Metfomin plus Simvastatin in people with Polycystic Ovary Syndrome, run by Fasa University of Medical Sciences at 1 site in Iran.
Trial summary
Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 6.5%-6.7% of women in reproductive age, and is commonly associated with obesity, menstrual irregularity, insulin resistance (IR), infertility, and clinical hyperandrogenism and/or hyperandrogenemia (1,2). Read more about this study
- Who is it for?
- Ages 16 to 45 years, women only
- Conditions the study is for
- Polycystic Ovary Syndrome
- What is being tested?
- Metfomin plus Simvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 84 participants
- Where
- 1 siteIran
- Study dates
- Jan 2008to Nov 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients should have at least two of three following criteria: I) chronic anovulation, II) clinical and/or biochemical evidence of androgen excess and III) polycystic-appearing ovaries on transvaginal ultrasound.
Who cannot join
- Patients with Cushing's syndrome, hyperprolactinemia, diabetes mellitus (DM), thyroid disease, adrenal hyperplasia and androgen-secreting tumors or other endocrinopathies, will be excluded from the study.
- Patients with adrenal hyperplasia will be excluded by ACTH-stimulated 17-hydroxyprogesterone levels less than 10 ng/ml (15), and ACTH-stimulated 11-deoxycortisol levels less than 21 ng/ml [3-fold the 95th percentile (16) of a historical control group of 60 healthy women controls].
- Those subjects who have kidney or liver diseases and those who were smoker or had breast cancer will also be excluded from the study.
- None of the participants receive oral contraceptives (OCPs), steroid hormones or any medications that interfere with lipid metabolism, ovarian and pituitary and hypothalamic function, or insulin sensitivity in the last 3 months before study.
Trial locations and contacts
1 site in 1 country.
About this study
Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 6.5%-6.7% of women in reproductive age, and is commonly associated with obesity, menstrual irregularity, insulin resistance (IR), infertility, and clinical hyperandrogenism and/or hyperandrogenemia (1,2). PCOS is also associated with increased risk of abnormal lipoproteins and hypertension, as well as cardiovascular or cerebrovascular morbidity (3). The lipid and lipoprotein profile in androgenized women with poly cystic ovaries is similar to the made pattern with higher levels of cholesterol, low-density lipoprotein (LDL), and lower levels of high-density lipoprotein (HDL), and this abnormal pattern is independent of body weight (4). Insulin resistance is associated with reproductive abnormalities in women with PCOS. Improving insulin sensitivity through both lifestyle and pharmacological intervention can ameliorate these abnormalities. Insulin resistance in women with PCOS is common (up to 50%), both in obese and nonobese women (5), and disordered insulin action precedes the increase in androgen.
Treatment for PCOS subjects typically includes, implementation of lifestyle changes especially weight loss and adjuvant pharmaceutical intervention including oral contraceptives, anti-androgen therapy and insulin-lowering drugs (such as, metformin) (6). Metformin is a biguanide used extensively in type 2 diabetes. It inhibits hepatic glucose production and increases peripheral insulin sensitivity, but dose not cause hypoglycemia. Several studies have shown an increase in insulin sensitivity and pregnancy rate accompanied by decreased insulin and androgen levels in PCOS patients taking metformin (7).
Read more
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase inhibitors (statins) are the rate-limiting step in cholesterol biosynthesis, and inhibition of this enzyme decreases cholesterol synthesis and a compensatory increase in the expression of LDL receptors in the liver. Statins reduce plasma triglycerides in dose-dependent fashion and also have a modest HDL-raising effect which is not dose-dependent (8,9). Furthermore, statins pose other cardio-protective properties, including antioxidant and anti-inflammatory actions (10,11).
Some studies have reported that simvastatin decreases serum androgen levels in women with PCOS (12,13) by inhibiting proliferation and steroidogenesis of ovarian theca-interstitial cells (14). According to these previous findings, we hypothesized that combination therapy with simvastatin and metformin will result in lower androgen levels and cardiovascular risk factors in women with PCOS.
- Conditions
- Polycystic Ovary Syndrome
- Being tested
- Metformin plus Placebo, Metfomin plus Simvastatin
- Keywords
- Polycystic ovary syndrome, Metformin, Simvastatin
- Medical subject headings
- Polycystic Ovary Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin plus PlaceboDrug
PCOS patients(n=42) will be assigned to the placebo (once/day) plus metformin (500mg three times a day, n=42; group 2)
Metfomin plus SimvastatinDrug
| Study group | Role | What they receive |
|---|---|---|
| Metformin plus Simvastatin | Active comparator | PCOS patients(n=42) will be assigned to the simvastatin (20mg/day) plus metformin (500mg three times a day, n=42; group 1) Receives: Drug: Metfomin plus Simvastatin |
| Metformin plus Placebo | Placebo comparator | PCOS patients(n=42) will be assigned to the placebo (once/day) plus metformin (500mg three times a day, n=42; group 2) Receives: Drug: Metformin plus Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum total testosterone
Measured: 6 weeks
Secondary outcomes (1)
Lipid profile BMI (kg/m2) Total Chol. (mg/dl) HDL (mg/dl) LDL (mg/dl) TG (mg/dl) Testosterone (ng/ml) LH (mIU/ml) FSH (mIU/ml) LH/FSH DHEAS (microgr/dL) Hirsutism score Prolactin (ng/dL) FBS (mg/dL) Fasting Insulin (μU/ml) QUICKI index
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2009 (estimated)
- Study startJan 2008
- Primary completionMar 2009
- Study completionNov 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Polycystic Ovary SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 84 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fasa University of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Shiraz University of Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01021579
- Sponsor's protocol ID
- SUMS 84-258
- Status last verified
- Nov 2009
- First submitted
- 23 Nov 2009
- Last updated
- 30 Nov 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 30 Nov 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Metformin Plus Simvastatin on Polycystic Ovarian Syndrome (PCOS): A Prospective, Randomized, Double-Blind, Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT01021579
- Acronym / sponsor ID
- SUMS 84-258
- Conditions
- Polycystic Ovary Syndrome
- Keywords
- Polycystic ovary syndrome, Metformin, Simvastatin
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 84 participants (estimated)
- Lead sponsor
- Fasa University of Medical SciencesUniversity, hospital or other
- Collaborators
- Shiraz University of Medical Sciences
- Study start
- Jan 2008
- Primary completion
- Mar 2009 (actual)
- Study completion
- Nov 2009 (actual)
- First posted
- 30 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Polycystic ovary syndrome (PCOS) is a common endocrinopathy affecting 6.5%-6.7% of women in reproductive age, and is commonly associated with obesity, menstrual irregularity, insulin resistance (IR), infertility, and clinical hyperandrogenism and/or hyperandrogenemia (1,2). PCOS is also associated with increased risk of abnormal lipoproteins and hypertension, as well as cardiovascular or cerebrovascular morbidity (3). The lipid and lipoprotein profile in androgenized women with poly cystic ovaries is similar to the made pattern with higher levels of cholesterol, low-density lipoprotein (LDL), and lower levels of high-density lipoprotein (HDL), and this abnormal pattern is independent of body weight (4). Insulin resistance is associated with reproductive abnormalities in women with PCOS. Improving insulin sensitivity through both lifestyle and pharmacological intervention can ameliorate these abnormalities. Insulin resistance in women with PCOS is common (up to 50%), both in obese and nonobese women (5), and disordered insulin action precedes the increase in androgen.
Treatment for PCOS subjects typically includes, implementation of lifestyle changes especially weight loss and adjuvant pharmaceutical intervention including oral contraceptives, anti-androgen therapy and insulin-lowering drugs (such as, metformin) (6). Metformin is a biguanide used extensively in type 2 diabetes. It inhibits hepatic glucose production and increases peripheral insulin sensitivity, but dose not cause hypoglycemia. Several studies have shown an increase in insulin sensitivity and pregnancy rate accompanied by decreased insulin and androgen levels in PCOS patients taking metformin (7).
The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-COA) reductase inhibitors (statins) are the rate-limiting step in cholesterol biosynthesis, and inhibition of this enzyme decreases cholesterol synthesis and a compensatory increase in the expression of LDL receptors in the liver. Statins reduce plasma triglycerides in dose-dependent fashion and also have a modest HDL-raising effect which is not dose-dependent (8,9). Furthermore, statins pose other cardio-protective properties, including antioxidant and anti-inflammatory actions (10,11).
Some studies have reported that simvastatin decreases serum androgen levels in women with PCOS (12,13) by inhibiting proliferation and steroidogenesis of ovarian theca-interstitial cells (14). According to these previous findings, we hypothesized that combination therapy with simvastatin and metformin will result in lower androgen levels and cardiovascular risk factors in women with PCOS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Metformin plus Simvastatin | Active comparator | Drug: Metfomin plus SimvastatinPCOS patients(n=42) will be assigned to the simvastatin (20mg/day) plus metformin (500mg three times a day, n=42; group 1) |
| Metformin plus Placebo | Placebo comparator | Drug: Metformin plus PlaceboPCOS patients(n=42) will be assigned to the placebo (once/day) plus metformin (500mg three times a day, n=42; group 2) |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (1 listed)
- All patients should have at least two of three following criteria: I) chronic anovulation, II) clinical and/or biochemical evidence of androgen excess and III) polycystic-appearing ovaries on transvaginal ultrasound.
Key exclusion criteria (4 listed)
- Patients with Cushing's syndrome, hyperprolactinemia, diabetes mellitus (DM), thyroid disease, adrenal hyperplasia and androgen-secreting tumors or other endocrinopathies, will be excluded from the study.
- Patients with adrenal hyperplasia will be excluded by ACTH-stimulated 17-hydroxyprogesterone levels less than 10 ng/ml (15), and ACTH-stimulated 11-deoxycortisol levels less than 21 ng/ml [3-fold the 95th percentile (16) of a historical control group of 60 healthy women controls].
- Those subjects who have kidney or liver diseases and those who were smoker or had breast cancer will also be excluded from the study.
- None of the participants receive oral contraceptives (OCPs), steroid hormones or any medications that interfere with lipid metabolism, ovarian and pituitary and hypothalamic function, or insulin sensitivity in the last 3 months before study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin plus PlaceboPCOS patients(n=42) will be assigned to the placebo (once/day) plus metformin (500mg three times a day, n=42; group 2) | Drug | Metformin plus Placebo |
| Metfomin plus Simvastatin | Drug | Metformin plus Simvastatin |
Primary outcome
Serum total testosterone
Time frame: 6 weeks
1 secondary outcome
Lipid profile BMI (kg/m2) Total Chol. (mg/dl) HDL (mg/dl) LDL (mg/dl) TG (mg/dl) Testosterone (ng/ml) LH (mIU/ml) FSH (mIU/ml) LH/FSH DHEAS (microgr/dL) Hirsutism score Prolactin (ng/dL) FBS (mg/dL) Fasting Insulin (μU/ml) QUICKI index
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Nov 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metfomin plus Simvastatin in people with Polycystic Ovary Syndrome, run by Fasa University of Medical Sciences at 1 site in Iran.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Nov 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Iran. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum total testosterone (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Nov 2009.