Effects of Simvastatin on Uterine Leiomyoma Size

Leiomyoma Clinical Trial

Official title:

A Double-blinded, Phase II, Randomized Control Trial to Study the Effects of Simvastatin in Patients With Uterine Leiomyoma

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03400826
• Other study ID #: IRB00149869
• Secondary ID: 1R01HD094380-01
• Status: Recruiting
• Phase: Phase 2
• Start date: August 20, 2018
• Est. completion date: December 1, 2024

Study information

• Verified date: January 2024
• Source: Johns Hopkins University
• Contact: Mostafa Borahay, MD, PhD
• Phone: (410) 550-0337
• Email: mboraha1[@]jhmi.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims to study the effect of simvastatin on the size of uterine fibroids.

Description:

The study is a phase II double blinded clinical trial to determine feasibility, safety and preliminary clinical efficacy of simvastatin to reduce leiomyoma size. Women with symptomatic fibroids planned to undergo surgical management for fibroids such as hysterectomy or myomectomy will be screened for participation. The eligible women will undergo pre-study evaluation to ascertain study eligibility.The study will enroll 60 participants in total, half will receive simvastatin and the other half will receive a placebo. The study drug and placebo will be an add on to the participants ongoing medical management of fibroids until surgery. The participants will be monitored at intervals for the effect of the drug on fibroid size and symptoms using ultrasound and quality of life questionnaires.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 1, 2024
• Est. primary completion date: July 31, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Signed informed written consent.

• Gender: female.

• Age: 18-55 years at time of signing consent.

• BMI of subjects: < 45 kg/m2.

• Uterine fibroids:

• Diagnosed by ultrasound (MRI will be used only if ultrasound is inconclusive).

• Number: any number of fibroids.

• Location: submucosal or intramural.

• At least one fibroid of diameter > 3cm.

• Symptoms: one or more of the following symptoms of heavy menstrual bleeding (HMB), defined as: Experienced cyclic (22 to 35 days) abnormal uterine bleeding (heavy or prolonged) in at least 3 of the last 6 menstrual periods, including menstrual bleeding lasting 5 or more days or heavy bleeding per participant recall. Examples of heavy bleeding may include, but are not limited to the following:

• Requires the use of double protection to manage menstrual bleeding.

• Menstrual bleeding accompanied by the sensation of "gushing" or "flooding".

• Saturates more than 1 tampon or sanitary pad per hour for 3 or more consecutive hours.

• Regularly needs to change the tampon or sanitary pad at night or regularly soils bedclothes.

• Heavy bleeding that affects work, school, or social activities.

• Pelvic pain/ pressure likely caused by fibroids.

• Plan for surgery (hysterectomy or myomectomy).

• Normal Pap smear within the last year.

• Use of contraception during study such as non-hormonal oral contraceptives, intrauterine devices (IUD)/ intrauterine systems (IUS), barrier contraceptives, abstinence or sterilization.

Exclusion Criteria:

• Pregnancy or lactation.

• Previous or current uterine, cervical or ovarian cancer.

• Current endometrial hyperplasia or history of atypical endometrial hyperplasia. Endometrial biopsy will be done during screening (if not done within last 12 months).

• Suspicion of leiomyosarcoma.

• Recent rapid growth of fibroids (i.e. doubling in size within 1-6 months period).

• Unevaluated gynecologic abnormalities (unexplained vaginal bleeding, cervical dysplasia, or abnormal adnexal/ovarian mass).

• Menopausal status.

• Surgery is urgently indicated (< 3 months) for medical or social reasons.

• Hemoglobin = 6 g/dL.

• Currently enrolled in another investigational study.

• Mental condition or other barrier preventing informed written consent.

• Allergy or hypersensitivity to simvastatin.

• Current use of simvastatin or other drugs of the same class.

• Concomitant administration of strong CYP3A4 inhibitors including itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors, boceprevir, telaprevir, nefazodone, and cobicistat-containing products.

• Concomitant administration of gemfibrozil, cyclosporine, or danazol, verapamil, diltiazem, amiodarone, diltiazem, dronedarone, amlodipine, ranolazine, lomitapide, and grapefruit juice.

• Active liver disease, which may include unexplained persistent elevations in hepatic transaminase levels.( elevation of aspartate transaminase and/or alanine transaminase > 2 s.d. above the normal range at screening visit)

• Known increased risk or diagnosis of a myopathy.

Related Conditions & MeSH terms

• Fibroid Tumor
• Fibroid Uterus
• Fibromyoma
• Leiomyoma
• Leiomyoma, Uterine

Intervention

Drug:
• Simvastatin 40mg
The Treatment Group subjects will orally intake encapsulated Simvastatin 40 mg tablets daily for the 12 weeks duration with water in the evening.
• Placebo 40 mg
The Placebo group will orally intake encapsulated Starch 1500, 40 mg Placebo for 12 weeks duration with water in the evening.

Locations

Country	Name	City	State
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (3)

Lead Sponsor	Collaborator
Johns Hopkins University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse events reporting by organ systems	Based on patient reporting and study team evaluation utilizing CTCAE v.4	At visit 2 (start of the study drug intake), visit 3 (6 weeks after start of the study drug), visit 4 (12 weeks after start of the study drug), and follow up visit at 2 and 6 weeks post hysterectomy.
Primary	Change in Tumor size volume pre and post study intervention	Tumor size measured by ultrasound imaging comparing tumor volume using ultrasound imaging. The volume will be reported in Centimeter cubes. The largest radius of the tumor will be used to calculate the volume, this will be measured in centimeters.	Change from baseline to 12 weeks post intervention
Secondary	Clinical symptom improvement as determined by the Uterine Fibroid Symptom and Health Related Quality of Life Questionnaire.	The questionnaire used is the Uterine Fibroid Symptom and Health Related Quality of Life Questionnaire. This questionnaire is an effective and validated tool for detecting differences in symptom severity and health-related quality of life among patients with uterine fibroids. The scale for this questionnaire denotes symptom severity with lowest and highest possible scores of 8 and 40 respectively. Higher scores indicate greater severity of symptoms.	At visit 1 (Screening), At visit 2 (start of the study drug intake), visit 3 (6 weeks after start of the study drug), visit 4( 12 weeks after start of the study drug), and follow up visit at 2 and 6 weeks post hysterectomy
Secondary	Adherence to the recommended treatment dosing	Based on review of patient diaries and counting of left over medications bought back by the subject. This will be reported as an overall percentage.	At Visit 3 (6 weeks after start of study drug), and Visit 4 (12 weeks after start of the study drug)
Secondary	Subject retention	Based on presence at follow up visits to the study site. This will be determined as a simple percentage of subjects that stay in the study until the last visit.	At visit 2 (start of the study drug intake), visit 3 (6 weeks after start of the study drug), visit 4 (12 weeks after start of the study drug), and follow up visit at 2 and 6 weeks post hysterectomy.