Clinical Trials /

Effects of Simvastatin on Uterine Leiomyoma Size

NCT03400826

Description:

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

Related Conditions:
  • Uterine Corpus Leiomyoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • 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

Clinical Trial IDs

  • ORG STUDY ID: IRB00149869
  • SECONDARY ID: 1R01HD094380-01
  • NCT ID: NCT03400826

Conditions

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

Interventions

DrugSynonymsArms
Simvastatin 40mgSimvastatinTreatment Group
Placebo 40 mgStarch 1500 encapsulatedPlacebo Group

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment GroupExperimentalThe 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.
  • Simvastatin 40mg
Placebo GroupPlacebo ComparatorThe 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.
  • Placebo 40 mg

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.
      
Maximum Eligible Age:55 Years
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Change in Tumor size volume pre and post study intervention
Time Frame:Change from baseline to 12 weeks post intervention
Safety Issue:
Description: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

Measure:Clinical symptom improvement as determined by the Uterine Fibroid Symptom and Health Related Quality of Life Questionnaire.
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
Safety Issue:
Description: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.
Measure:Adherence to the recommended treatment dosing
Time Frame:At Visit 3 (6 weeks after start of study drug), and Visit 4 (12 weeks after start of the study drug)
Safety Issue:
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.
Measure:Subject retention
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.
Safety Issue:
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.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Johns Hopkins University

Trial Keywords

  • simvastatin
  • fibroids
  • medical management
  • uterine fibroids
  • leiomyoma

Last Updated

August 17, 2020