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

NCT04113889 | Completed Phase 2 DMC

• 1 other identifier: ASRB001062/ET/IBMS
• Study Type: interventional
• Target: 147
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

PCOS

Keywords

PCOS; Acetyl-L-Carnitine

Outcome Measures

Primary Outcomes (4)

• Insulin resistance

  PCOS associated insulin resistance and hyperinsulinemia through HOMA-IR

  3 months

• Hypoadiponectinemia

  PCOS associated Hypoadiponectinemia. Measurement of adiponectin level through ELISA

  3 months

• Ovary volume

  Polycystic ovaries volume measurement by abdominal ultrasound

  3 months

• Stress response

  Perceived stress response and profile of mood stress by structured questionnaire

  3 months

Secondary Outcomes (5)

• Body fat analysis

  3 months

• Hirsutism

  3 months

• Menstrual irregularities

  3 months

• Androgenic Alopecia

  3 months

• Pregnancy

  3 months

Study Arms (2)

Combination therapy group

ACTIVE COMPARATOR

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)

Standard therapy group

PLACEBO COMPARATOR

Arm 2: Metformin (1000 mg daily), Pioglitazone (30 mg daily), Placebo

Drug: Metformin, pioglitazone and placebo

Interventions

Metformin (1000 mg daily), Pioglitazone (30 mg daily), Acetyl-L-carnitine (3 gm daily) DRUG

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

Combination therapy group

Metformin, pioglitazone and placebo DRUG

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

Standard therapy group

Eligibility Criteria

• Age: 15 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Hirsutism or hyperandrogenism
• Oligo or an-ovulation and or polycystic ovaries -

You may not qualify if:

• Women with previous history of Cushing syndrome
• Thyroid disorders
• Hyperprolactinemia
• Ovarian tumors
• Congenital adrenal hyperplasia androgen-producing tumors,
• History of seizures
• Patients on warfarin, Coumadin and Sintrom because of drug interaction with acetyl-L-Carnitine,
• Pregnancy or using contraceptive medications,
• Patients on hormonal therapy that alters the biochemical or hormonal profile

Sponsors & Collaborators

• Khyber Medical University Peshawar: lead

Study Sites (1)

Gynecology and Obstetric, Hayatabad Medical Complex

Peshawar, Khyber Pukhtunkhwa, 25000, Pakistan

Location

Related Publications (8)

• Nestler JE, Stovall D, Akhter N, Iuorno MJ, Jakubowicz DJ. Strategies for the use of insulin-sensitizing drugs to treat infertility in women with polycystic ovary syndrome. Fertil Steril. 2002 Feb;77(2):209-15. doi: 10.1016/s0015-0282(01)02963-6.

  PMID: 11821072 BACKGROUND

• Elkind-Hirsch K, Marrioneaux O, Bhushan M, Vernor D, Bhushan R. Comparison of single and combined treatment with exenatide and metformin on menstrual cyclicity in overweight women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2008 Jul;93(7):2670-8. doi: 10.1210/jc.2008-0115. Epub 2008 May 6.

  PMID: 18460557 BACKGROUND

• Glintborg D, Andersen M, Hagen C, Heickendorff L, Hermann AP. Association of pioglitazone treatment with decreased bone mineral density in obese premenopausal patients with polycystic ovary syndrome: a randomized, placebo-controlled trial. J Clin Endocrinol Metab. 2008 May;93(5):1696-701. doi: 10.1210/jc.2007-2249. Epub 2008 Feb 19.

  PMID: 18285411 BACKGROUND

• Xu Y, Wu Y, Huang Q. Comparison of the effect between pioglitazone and metformin in treating patients with PCOS:a meta-analysis. Arch Gynecol Obstet. 2017 Oct;296(4):661-677. doi: 10.1007/s00404-017-4480-z. Epub 2017 Aug 2.

  PMID: 28770353 BACKGROUND

• Ismail AM, Hamed AH, Saso S, Thabet HH. Adding L-carnitine to clomiphene resistant PCOS women improves the quality of ovulation and the pregnancy rate. A randomized clinical trial. Eur J Obstet Gynecol Reprod Biol. 2014 Sep;180:148-52. doi: 10.1016/j.ejogrb.2014.06.008. Epub 2014 Jun 23.

  PMID: 25015747 BACKGROUND

• Rajasekar P, Anuradha CV. Effect of L-carnitine on skeletal muscle lipids and oxidative stress in rats fed high-fructose diet. Exp Diabetes Res. 2007;2007:72741. doi: 10.1155/2007/72741.

  PMID: 17641743 BACKGROUND

• Bernard A, Rigault C, Mazue F, Le Borgne F, Demarquoy J. L-carnitine supplementation and physical exercise restore age-associated decline in some mitochondrial functions in the rat. J Gerontol A Biol Sci Med Sci. 2008 Oct;63(10):1027-33. doi: 10.1093/gerona/63.10.1027.

  PMID: 18948552 BACKGROUND

• Tauqir S, Israr M, Rauf B, Malik MO, Habib SH, Shah FA, Usman M, Raza MA, Shah I, Badshah H, Ehtesham E, Shah M. Acetyl-L-Carnitine Ameliorates Metabolic and Endocrine Alterations in Women with PCOS: A Double-Blind Randomized Clinical Trial. Adv Ther. 2021 Jul;38(7):3842-3856. doi: 10.1007/s12325-021-01789-5. Epub 2021 May 28.

  PMID: 34047916 DERIVED

MeSH Terms

Interventions

Metformin; Pioglitazone; Acetylcarnitine

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Thiazolidinediones; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carnitine; Trimethyl Ammonium Compounds; Quaternary Ammonium Compounds; Amines

Study Officials

• Mohsin Shah, PhD

  Department of Physiology, Khyber Medical University, Peshawar Pakistan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: September 26, 2019
• First Posted: October 3, 2019
• Study Start: October 15, 2019
• Primary Completion: January 30, 2020
• Study Completion: January 30, 2020
• Last Updated: February 5, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1)