The Effect of Simvastatin on Uterine Leiomyoma Development and Growth in Infertile Women

Evaluation the Effect of Simvastatin on Uterine Leiomyoma Development and Growth in Infertile Patients

Uterine leiomyomas with an estimated incidence of 50%-80% are the most common tumors of female reproductive system. Statins as a HMG-CoA reductase inhibitors inhibit the mevalonate pathway of cholesterol synthesis, thus have been known as a group of drugs used for treatment of hypercholesterolemia. Statins inhibit proliferation of several cell types including vascular smooth muscle, hepatocytes and other cell types. Leiomyomas are benign uterine tumors characterized by smooth muscle proliferation and excessive deposition of extracellular matrix. In the present study we aim to evaluate the effect of simvastatin on uterine leiomyoma development and growth.

Study Overview

• Status: Unknown
• Conditions: Infertility
• Intervention / Treatment: Drug: oral drug and vaginal placebo; Drug: oral drug and oral placebo; Drug: Vaginal placebo+ oral placebo

Detailed Description

The proposal of the present study approved by our institutional review boards and institution's ethical committee, and all participants will sign a written consent before enter to study. All patients will be randomly divided into three groups and will be randomized to receive simvastatin 40 mg orally + vaginal placebo, simvastatin 40 mg vaginally + oral placebo and vaginal placebo + oral placebo for 3 months.

CBC, Lipid profile, kidney & Liver function tests, FBS & hormonal evaluation will be performed before and after the treatment. Ultrasound examination will be performed before and after the treatment for determining of the number, size, and site of the myoma and also size of the uterus.

• Study Type: Interventional
• Enrollment (Anticipated): 60
• Phase: Phase 3

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehrān, Iran, Islamic Republic of
    • Recruiting
    • Royan Institute
    • Contact: Nasser Aghdami, MD,PhD; Phone Number: 516 (+98)2123562000; Email: nasser.aghdami@royaninstitute.org
    • Contact: Leila Arab, MD; Phone Number: 414 (+98)2123562000; Email: Leara91@gmail.com
    • Principal Investigator: Firoozeh Ghafari, MD
    • Principal Investigator: Elham Amirchaghmaghi, MD,PhD
    • Sub-Investigator: Farnaz Akbari, MSc
    • Sub-Investigator: Amir Almasi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Age between 20-40 years
• Intramural Fibroids confirmed by ultrasound
• Presence of at least one fibroid with size >4 cm or two fibroids with size >3 cm detected by pelvic ultrasound.
• Presence of at least 3 fibroids with size <3 cm and a history of 2 IVF failures.
• Number of fibroids ≤ 5
• BMI>25 Kg/m2

Exclusion Criteria:

• Pregnancy
• Hormonal contraception or any hormonal therapy received in the last 3 months
• Alcohol consumption
• Allergic to simvastatin
• Suspicion or diagnosis of cancer
• Signs or symptoms of mental illness, hepatic dysfunction, myopathic syndromes, diabetes mellitus, renal disease, Cardiovascular disease, hypothyroidism, hypotension, neuropathy, lupus and cataract
• Hb ≤ 7
• Taking antifungal medications, Lipid-Lowering medications (gemfibrozil, clofibrate), warfarin, danazol and erythromycin in the last one month.
• Severe male factor
• Severe endometriosis
• Diminished ovarian reserve

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Simvastatin and vaginal placebo; The patients with leiomyoma receive simvastatin 40 mg orally+ vaginal placebo will be given every day for 3 months.	Drug: oral drug and vaginal placebo; prescription of simvastatin 40 mg orally+ vaginal placebo every day for 3 months.
Experimental: Simvastatin and oral placebo; The patients with leiomyoma receive simvastatin 40 mg orally+ oral placebo will be given every day for 3 months.	Drug: oral drug and oral placebo; prescription of simvastatin 40 mg orally+ oral placebo every day for 3 months.
Experimental: Vaginal placebo+ oral placebo; The patients with leiomyoma receive Vaginal placebo+ oral placebo every day for 3 months.	Drug: Vaginal placebo+ oral placebo; prescription of Vaginal placebo + oral placebo every day for 3 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine fibroid size	Evaluation the size of Uterine fibroid withultrasound.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Uterine size	Evaluation the uterine size with ultrasound.	3months
Plasma concentration of Vitamin D3	Evaluation the Plasma concentration of Vitamin D3 with blood sampling.	3 months

Collaborators and Investigators

• Sponsor: Royan Institute
• Investigators: Study Director: Mahnaz Ashrafi, MD, ) Endocrinology and Female Infertility Department, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Study Director: Firoozeh Ahmadi, MD, ) Endocrinology and Female Infertility Department, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran; Principal Investigator: Nadia Jahangiri, MSc, ) Endocrinology and Female Infertility Department, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2016
• Primary Completion (Anticipated): June 14, 2021
• Study Completion (Anticipated): September 14, 2021

Study Registration Dates

• First Submitted: April 26, 2017
• First Submitted That Met QC Criteria: April 26, 2017
• First Posted (Actual): April 28, 2017

Study Record Updates

• Last Update Posted (Actual): October 6, 2020
• Last Update Submitted That Met QC Criteria: October 5, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Keywords: Leiomyoma simvastatin infertility
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Connective Tissue Diseases; Neoplasms, Connective Tissue; Neoplasms, Muscle Tissue; Infertility; Leiomyoma; Myofibroma
• Other Study ID Numbers: Royan-Emb-029

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