Effects of Triple Drug Cocktail Therapy on Metabolic, Endocrine Alterations and Perceived Stress in Patients With Poly Cystic Ovary Syndrome
Condition: PCOS
Study type: Interventional
Phase: Phase 2

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily); Metformin, pioglitazone and placebo
Intervention type(s): Drug; Drug
Intervention description(s): 72 patients with PCOS receiving metformin, pioglitazone and Acetyl L-Carnitine 500 mg, 15 mg and 1.5 gm BD daily respectively.; 72 patients with PCOS receiving metformin, pioglitazone and placebo 500 mg, 15 mg and placebo BD daily respectively.
Other intervention name(s): Zolid plus and Acetyl-L-carnitine; Zolid plus and placebo
Intervention MeSH terms: Acetylcarnitine; Metformin; Pioglitazone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Treatment
Keywords: PCOS; Acetyl-L-Carnitine