A Phase 2 interventional study of Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily) and Metformin, pioglitazone and placebo in PCOS, sponsored by Khyber Medical University Peshawar. Completed at 1 site in Pakistan. Open to female participants aged 15 Years to 45 Years. Per ClinicalTrials.gov, last updated 2020-02-05.
Sponsored by Khyber Medical University Peshawar · Phase 2, Interventional, and Treatment
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.
Khyber Medical University Peshawar is the lead sponsor of 53 studies on the registry; 12 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Arm 1: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily)
Drug: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily)
Arm 2: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Placebo
Drug: Metformin, pioglitazone and placebo
72 patients with PCOS receiving metformin, pioglitazone and Acetyl L-Carnitine 500 mg, 15 mg and 1.5 gm BD daily respectively.
Also known as: Zolid plus and Acetyl-L-carnitine
72 patients with PCOS receiving metformin, pioglitazone and placebo 500 mg, 15 mg and placebo BD daily respectively.
Also known as: Zolid plus and placebo
Insulin resistance
PCOS associated insulin resistance and hyperinsulinemia through HOMA-IR
Time frame: 3 months
Hypoadiponectinemia
PCOS associated Hypoadiponectinemia. Measurement of adiponectin level through ELISA
Time frame: 3 months
Ovary volume
Polycystic ovaries volume measurement by abdominal ultrasound
Time frame: 3 months
Stress response
Perceived stress response and profile of mood stress by structured questionnaire
Time frame: 3 months
Body fat analysis
Body fats measurement through measurement scale
Time frame: 3 months
Hirsutism
Hirsutism score
Time frame: 3 months
Menstrual irregularities
Oligo/anovulation
Time frame: 3 months
Androgenic Alopecia
Hair on head area
Time frame: 3 months
Pregnancy
Fertility/infertility
Time frame: 3 months
Plan to share: No
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Khyber Medical University Peshawar