Clinical trial NCT03400826: 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
Overall status: RECRUITING
Phase: PHASE2
Conditions: Fibroid Uterus
Fibroid Tumor
Leiomyoma
Fibromyoma
Leiomyoma, Uterine
Keywords: simvastatin
fibroids
medical management
uterine fibroids
leiomyoma
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2018-01-17
Enrollment: 60
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Tumor size volume pre and post study intervention
timeFrame: Change from baseline to 12 weeks post intervention
Secondary outcomes:
measure: Clinical symptom improvement as determined by the Uterine Fibroid Symptom and Health Related Quality of Life Questionnaire.
timeFrame: 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
measure: Adherence to the recommended treatment dosing
timeFrame: At Visit 3 (6 weeks after start of study drug), and Visit 4 (12 weeks after start of the study drug)
measure: Subject retention
timeFrame: 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 outcomes:
measure: Adverse events reporting by organ systems
timeFrame: 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.
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins Hospital
state: Maryland
Study officials:
affiliation: Johsn Hopkins School Of Medicine
name: Mostafa Borahay, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: