Effects of Triple Drug Cocktail Therapy on Metabolic, Endocrine Alterations and Perceived Stress in Patients With Poly Cystic Ovary Syndrome (PCOS)

January 30, 2020 updated by: Mohsin Shah, Khyber Medical University Peshawar

Effects of Triple Drug Cocktail Therapy on Metabolic, Endocrine Alterations and Perceived Stress Response in Patients With PCOS: A Double Blind Randomized Clinical Trial

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

147

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Pakistan
    • Khyber Pukhtunkhwa
      • Peshawar, Khyber Pukhtunkhwa, Pakistan, 25000
        • Gynecology and Obstetric, Hayatabad Medical Complex

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

13 years to 43 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Combination therapy group
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)
72 patients with PCOS receiving metformin, pioglitazone and Acetyl L-Carnitine 500 mg, 15 mg and 1.5 gm BD daily respectively.
Other Names:
  • Zolid plus and Acetyl-L-carnitine
Placebo Comparator: Standard therapy group
Arm 2: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Placebo
Drug: Metformin, pioglitazone and placebo
72 patients with PCOS receiving metformin, pioglitazone and placebo 500 mg, 15 mg and placebo BD daily respectively.
Other Names:
  • Zolid plus and placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Stress response
Time Frame: 3 months
Perceived stress response and profile of mood stress by structured questionnaire
3 months
Insulin resistance
Time Frame: 3 months
PCOS associated insulin resistance and hyperinsulinemia through HOMA-IR
3 months
Hypoadiponectinemia
Time Frame: 3 months
PCOS associated Hypoadiponectinemia. Measurement of adiponectin level through ELISA
3 months
Ovary volume
Time Frame: 3 months
Polycystic ovaries volume measurement by abdominal ultrasound
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Body fat analysis
Time Frame: 3 months
Body fats measurement through measurement scale
3 months
Hirsutism
Time Frame: 3 months
Hirsutism score
3 months
Menstrual irregularities
Time Frame: 3 months
Oligo/anovulation
3 months
Androgenic Alopecia
Time Frame: 3 months
Hair on head area
3 months
Pregnancy
Time Frame: 3 months
Fertility/infertility
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Khyber Medical University Peshawar

Investigators

  • Principal Investigator: Mohsin Shah, PHD, Department of Physiology, Khyber Medical University, Peshawar Pakistan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 15, 2019

Primary Completion (Actual)

January 30, 2020

Study Completion (Actual)

January 30, 2020

Study Registration Dates

First Submitted

September 26, 2019

First Submitted That Met QC Criteria

October 2, 2019

First Posted (Actual)

October 3, 2019

Study Record Updates

Last Update Posted (Actual)

February 5, 2020

Last Update Submitted That Met QC Criteria

January 30, 2020

Last Verified

January 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ASRB001062/ET/IBMS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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