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Effects of Simvastatin on Uterine Leiomyoma Size

Primary Purpose

Fibroid Uterus, Fibroid Tumor, Leiomyoma

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Simvastatin 40mg

Placebo 40 mg

About this trial

This is an interventional treatment trial for Fibroid Uterus focused on measuring simvastatin, fibroids, medical management, uterine fibroids, leiomyoma

Eligibility Criteria

18 Years - 55 Years (Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

Johns Hopkins HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment Group

Placebo Group

Arm Description

The 30 participants randomized in this group will intake Simvastatin 40mg / day of orally at the same time in the evening, every day for the study duration of 12 weeks prior to undergoing hysterectomy/ myomectomy. The fibroid samples will be collected after the surgery to evaluate the effects of the study medication on the fibroid tissue.

The 30 participants randomized in this group will intake Placebo 40mg / day orally at the same time in the evening every day for the study duration of 12 weeks prior to undergoing hysterectomy/ myomectomy. The fibroid samples will be collected after the surgery to evaluate the effects of the study medication on the fibroid tissue.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT03400826

First Posted

January 9, 2018

Last Updated

August 9, 2023

Sponsor

Johns Hopkins University

Collaborators

National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

1. Study Identification

Unique Protocol Identification Number

NCT03400826

Brief Title

Effects of Simvastatin on Uterine Leiomyoma Size

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

August 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 20, 2018 (Actual)

Primary Completion Date

January 1, 2024 (Anticipated)

Study Completion Date

December 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Johns Hopkins University

Collaborators

National Institutes of Health (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

simvastatin, fibroids, medical management, uterine fibroids, leiomyoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment Group

Arm Type

Experimental

Arm Description

Arm Title

Placebo Group

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Simvastatin 40mg

Other Intervention Name(s)

Simvastatin

Intervention Description

The Treatment Group subjects will orally intake encapsulated Simvastatin 40 mg tablets daily for the 12 weeks duration with water in the evening.

Intervention Type

Drug

Intervention Name(s)

Placebo 40 mg

Other Intervention Name(s)

Starch 1500 encapsulated

Intervention Description

The Placebo group will orally intake encapsulated Starch 1500, 40 mg Placebo for 12 weeks duration with water in the evening.

Primary Outcome Measure Information:

Title

Change in Tumor size volume pre and post study intervention

Description

Time Frame

Change from baseline to 12 weeks post intervention

Secondary Outcome Measure Information:

Title

Clinical symptom improvement as determined by the Uterine Fibroid Symptom and Health Related Quality of Life Questionnaire.

Description

Time Frame

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

Title

Adherence to the recommended treatment dosing

Description

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.

Time Frame

At Visit 3 (6 weeks after start of study drug), and Visit 4 (12 weeks after start of the study drug)

Title

Subject retention

Description

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.

Time Frame

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.

Other Pre-specified Outcome Measures:

Title

Adverse events reporting by organ systems

Description

Based on patient reporting and study team evaluation utilizing CTCAE v.4

Time Frame

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.

10. Eligibility

Sex

Female

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Mostafa Borahay, MD, PhD

Phone

(410) 550-0337

mboraha1@jhmi.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mostafa Borahay, MD, PhD

Organizational Affiliation

Johsn Hopkins School Of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Johns Hopkins Hospital

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21218

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Mostafa Borahay, MD, PhD

Phone

410-550-0337

mboraha1@jhmi.edu

First Name & Middle Initial & Last Name & Degree

James Segars, MD

First Name & Middle Initial & Last Name & Degree

Gayane Yenokyan, PhD

First Name & Middle Initial & Last Name & Degree

Paul Driggers, PhD

First Name & Middle Initial & Last Name & Degree

Bhuchitra Singh, MBBS,MPH,MS

12. IPD Sharing Statement

Plan to Share IPD

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Effects of Simvastatin on Uterine Leiomyoma Size

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