Effects of Triple Drug Cocktail Therapy on Metabolic, Endocrine Alterations and Perceived Stress Response in Patients With PCOS: A Double Blind Randomized Clinical Trial
| Registry | NCT04113889, acronym PCOS |
|---|---|
| Status | Completed |
| Phase | Phase 2 |
| Study type | Interventional; randomized, parallel, masking: triple, treatment |
| Enrollment | 147 (Actual) |
| Sponsor | Khyber Medical University Peshawar (Other) |
| Conditions | PCOS |
| Interventions | Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily), Metformin, pioglitazone and placebo (Drug) |
| Dates | start 2019-10-15, primary completion 2020-01-30, completion 2020-01-30, first posted 2019-10-03, last updated 2020-02-05 |
| Locations | 1 site in Pakistan |
Related Papers Related Patents Related Grants Related Experts
All trials for PCOS All trials of Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily) All trials of Metformin, pioglitazone and placebo
The investigators aim is to conduct a double blind randomized clinical trial, to study the effects of triple drug cocktail (metformin, pioglitazone and acetyl L-Carnitine) therapy on metabolic, endocrine alterations and perceived stress response in patients with Polycystic Ovary Syndrome (PCOS). Women diagnosed with PCOS, using criteria proposed in November 2015, by the American Association of Clinical Endocrinologists (AACE), American College of Endocrinology (ACE), and Androgen Excess and PCOS Society (AES) for PCOS should include two of the following three criteria: chronic an ovulation, hyperandrogenism (clinical/biologic), and polycystic ovaries. The investigators propose that PCOS women may have altered metabolic, endocrine levels and increased perceived stress response and combination therapy may have beneficial influences on these parameters in women diagnosed with PCOS.
Polycystic Ovarian Syndrome (PCOS) is an endocrinopathy which affects 5-10% of reproductive age women (1). The three main features of the syndrome are polycystic ovaries, high levels of androgen in blood and chronic an-ovulation/oligo-an ovulation (2). Women with PCOS have a greater risk of developing hyperinsulinemia and insulin resistance (3). PCOS may lead to insulin resistance and dyslipidemia (3). Recent long-term follow up studies of the syndrome have shown that women suffering from the syndrome have hyperlipidemia and enhanced risk of cardiovascular diseases (3).
Recent evidence has demonstrated that anti-inflammatory drug treatments ameliorate insulin resistance. Metformin belongs to a family of drugs called the biguanides, currently used as an antihyperglycemic drug for treatment of type II diabetes mellitus (4). Around 15 years ago it was reported for the first time that use of metformin in PCOS effectively reduced insulin resistance (4). Increasing evidence has shown the importance of metformin not only in hyperinsulinemic patients but also in PCOS resolving several other issues like menstrual cycles, fertility, hormonal imbalance and metabolic syndromes (4). Pioglitazone is a drug from class thiazolidinedione (TZD) with hypoglycemic (anti-hyperglycemic, anti-diabetic) action in the management of type 2 diabetes (5). Recent studies have shown that pioglitazone may be considered a new treatment option for patients with PCOS, since it is able to restore normal menstrual cycle and have improved ovulation (6). Recent randomized placebo controlled clinical trials have also shown that it is associated with good serum lipid profile levels (7).
Acetyl L-Carnitine is an isomer synthesized by two amino acids lysine and methionin mainly distributed among skeletal and cardiac muscles in mammals (8, 9). Acetyl L-Carnitine is involved in fatty acid oxidation by transporting long chain fatty acids into mitochondria for oxidation to produce metabolic energy and have effects on oxidative metabolism of glucose in tissues (9). Acetyl L-Carnitine is known to regulate energy production (10). Studies have shown that patients treated with acetyl L-Carnitine have improved ovulation and pregnancy rates and is well tolerated by the patients (8). PCOS patients have shown reduced adiponectin levels associated with insulin resistance states and type 2 diabetes mellitus and treatment with L-Carnitine has shown reduced blood glucose levels, increased insulin sensitivity and also improved adiponectin levels, which can be attributed to L-carnitine-induced increase in beta-oxidation of fatty acids and basal metabolic rates (11).
PCOS is a systemic condition, an endocrinopathy whose etiology is still not understood. Correct treatment regimens of PCOS will not only improve menstrual cycles of the patients but will also improve the metabolic or endocrine parameters (2). PCOS sufferers are also known to have increased perceived stress response which will be considered in the study. Little evidences are available on combination therapy for treatment of PCOS patients. The aim of this study is to come up with a better treatment option to ameliorate the signs and symptoms associated with the disease.
Study objectives:
To find the effects of triple drug cocktail therapy (metformin, pioglitazone and acetyl L-Carnitine) on metabolic, endocrine alterations and perceived stress response in patients with PCOS.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Combination therapy group | Active comparator | Drug: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily) | Arm 1: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily) |
| Standard therapy group | Placebo comparator | Drug: Metformin, pioglitazone and placebo | Arm 2: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Placebo |
Sex: Female, ages: 15 Years to 45 Years
Inclusion Criteria: 1. Treatment naive PCOS women having age from 14-45 years with scanty or no menstruation, hirsutism and elevated serum androgen levels, will be diagnosed on the basis of AES (Androgen access society) guidelines 2006 according to which when two of the following criteria are present patient will be said to have the syndrome 2. Hirsutism or hyperandrogenism 3. Oligo or an-ovulation and or polycystic ovaries - Exclusion Criteria: 1. Women with previous history of Cushing syndrome 2. Thyroid disorders 3. Hyperprolactinemia 4. Ovarian tumors 5. Congenital adrenal hyperplasia androgen-producing tumors, 6. History of seizures 7. Patients on warfarin, Coumadin and Sintrom because of drug interaction with acetyl-L-Carnitine, 8. Pregnancy or using contraceptive medications, 9. Patients on hormonal therapy that alters the biochemical or hormonal profile
| Facility | City | Country | Status |
|---|---|---|---|
| Gynecology and Obstetric, Hayatabad Medical Complex | Peshawar, Khyber Pukhtunkhwa | Pakistan |