Safety of Simvastatin in LAM and TSC

Learn more about:
Related Clinical Trial
Doxycycline In Lymphangioleiomyomatosis (LAM) Effect of Fasting on the Size of Abdominal Lymphatic Tumors in Women Turmeric as Treatment in Epilepsy Study of the Disease Process of Lymphangioleiomyomatosis RAD001 Therapy of Angiomyolipomata in Patients With TS Complex and Sporadic LAM The Effectiveness and Safety of Vagus Nerve Stimulation for TRE The Effectiveness and Safety of Resective Epilepsy Surgery for TRE Roll-over Study to Collect and Assess Long-term Safety of Everolimus in Patients With TSC and Refractory Seizures Who Have Completed the EXIST-3 Study [CRAD001M2304] and Who Are Benefitting From Continued Treatment Adjunctive Ganaxolone Treatment (Part A) in TSC Followed by Long-term Treatment (Part B) Safety of Simvastatin in LAM and TSC Studies of Autistic Patients: Gene Networks and Clinical Subtypes Topical Rapamycin to Erase Angiofibromas in TSC Rapalogues for Autism Phenotype in TSC: A Feasibility Study A Pilot Study To Evaluate The Effects of Everolimus on Brain mTOR Activity and Cortical Hyperexcitability in TSC and FCD Everolimus for Cancer With TSC1 or TSC2 Mutation Topical Sirolimus Ointment for Cutaneous Angiofibromas in Subjects With Tuberous Sclerosis Complex The Cognitive Variability in NF1 and TSC Monozygotic Twins Long-term Trial of Topical Sirolimus to Angiofibroma in Patient With Tuberous Sclerosis Complex Efficacy of RAD001/Everolimus in Autism and NeuroPsychological Deficits in Children With Tuberous Sclerosis Complex Phase III Trial of Topical Formulation of Sirolimus to Skin Lesions in Patients With Tuberous Sclerosis Complex (TSC) Topical Rapamycin Therapy to Alleviate Cutaneous Manifestations of Tuberous Sclerosis Complex (TSC) and Neurofibromatosis I (NF1) Trial of Efficacy and Safety of Sirolimus in Tuberous Sclerosis and LAM Long-term, Prospective Study Evaluating Clinical and Molecular Biomarkers of Epileptogenesis in a Genetic Model of Epilepsy – Tuberous Sclerosis Complex A Randomized Controlled Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6) An Open-label Extension Trial of Cannabidiol (GWP42003-P, CBD) for Seizures in Tuberous Sclerosis Complex (GWPCARE6) Aspirin as an add-on Treatment of Refractory Epilepsy in Tuberous Sclerosis Complex Autism Spectrum Disorder (ASD) and Intellectual Disability (ID) Determinants in Tuberous Sclerosis Complex (TSC) Clinical Presentation and Renal Outcome of Patients With Tuberous Sclerosis Complex and/or Renal Angiomyolipoma in the Great West Region of France Preventing Epilepsy Using Vigabatrin In Infants With Tuberous Sclerosis Complex Early Behavioral Intervention to Improve Social Communication Function in Infants With Tuberous Sclerosis Complex Characterization of Patients With Tuberous Sclerosis Complex, Lymphangioleiomyomatosis and Angiomyolipoma Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC) Everolimus (RAD001) Therapy of Giant Cell Astrocytoma in Patients With Tuberous Sclerosis Complex JASPER Early Intervention for Tuberous Sclerosis Studies in Patients With Tuberous Sclerosis Complex Treatment of Renal Angiomyolipomas in Tuberous Sclerosis by Beta-blockers Efficacy and Safety of RAD001 in Patients Aged 18 and Over With Angiomyolipoma Associated With Either Tuberous Sclerosis Complex (TSC) or Sporadic Lymphangioleiomyomatosis (LAM) Efficacy and Safety of Everolimus (RAD001) in Patients of All Ages With Subependymal Giant Cell Astrocytoma Associated With Tuberous Sclerosis Complex (TSC)(EXIST-1) Long Term Follow Up for RAD001 Therapy of Angiomyolipomata in Patients With Tuberous Sclerosis (TSC) and Sporadic Lymphangioleiomyomatosis (LAM) Dose-Ranging Efficacy and Safety Study of Topical Rapamycin Cream for Facial Angiofibroma Associated With Tuberous Sclerosis Complex Dermatologic Patterns of Tuberous Sclerosis Patients and Somatic Mutation Relationship Genetic Heterogeneity and Genotype-phenotype Correlation of Children and Adults With Tuberous Sclerosis Complex (TuScCom) Early Biomarkers of Autism in Infants With Tuberous Sclerosis Complex (TSC) Tuberous Sclerosis Complex Natural History Study: Renal Manifestations Rapamycin Therapy for Patients With Tuberous Sclerosis Complex and Sporadic LAM A Study of Everolimus in the Treatment of Neurocognitive Problems in Tuberous Sclerosis Trial of RAD001 and Neurocognition in Tuberous Sclerosis Complex (TSC) Study of Skin Tumors in Tuberous Sclerosis

Brief Title

Safety of Simvastatin in LAM and TSC

Official Title

The Safety of Simvastatin (SOS) in Patients With Pulmonary Lymphangioleiomyomatosis (LAM) and With Tuberous Sclerosis Complex (TSC)

Brief Summary

      The purpose of this research study is to see if simvastatin can be taken safely in patients
      with either LAM or TSC, who are already being treated with everolimus or sirolimus. This is
      the first step in looking at simvastatin as a drug that may help patients, by impacting the
      growth and survival of cells that make up the lung lesions that cause problems in LAM and TSC
      patients. The study also seeks to learn more about how simvastatin works, when given to
      patients being treated with everolimus or sirolimus, and to evaluate the safety and any
      potential benefit to patients taking this 2-drug combination.

      The primary objective of this study is to determine the safety of simvastatin in the
      treatment of LAM-S or LAM-TS in patients on a stable (for at least 3 months) dose of
      sirolimus or everolimus.

      Secondary objectives include:

        -  To assess the effect of simvastatin on forced expiratory volume in 1 second (FEV1).

        -  To assess the effect of simvastatin on forced vital capacity (FVC).

        -  To assess the effect of simvastatin on diffusing lung capacity (DLCO).

        -  To assess the effect of simvastatin on vascular endothelial growth factor -D (VEGF-D)
           serum levels.

        -  To assess the effect of simvastatin with questionnaire- based assessments of dyspnea,
           fatigue, and quality of life (QOL).

        -  Assess signs of clinical benefit.
    

Detailed Description

      After providing written informed consent, study related tests/procedures will be done to
      ensure eligibility for the study. If found to be eligible, the participant will be given
      simvastatin at a starting dose of 20 mg, to be taken each evening by mouth. If after 2 months
      the simvastatin 20 mg dose is tolerated, the dose of simvastatin will be increased to 40 mg
      each evening by mouth. Doses may be adjusted as needed, should the participant experience
      side effects from simvastatin. The participant's dose of everolimus or sirolimus is not
      expected to change, as this is a dose that has been previously tolerated. If side effects
      occur as a result of the combination of drugs, the dosages may be adjusted by the study
      physician (investigator).
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Safety of Simvastatin in the Treatment of LAM-S and LAM-TS Patients

Secondary Outcome

 Percent Predicted FEV1

Condition

Lymphangioleiomyomatosis

Intervention

Simvastatin

Study Arms / Comparison Groups

 simvastatin treatment arm
Description:  Eligible patients on sirolimus or everolimus will be assigned to receive 20 mg of simvastatin once daily for a period of two months. If tolerated, the dosage of simvastatin will be advanced to 40 mg once daily in months 3 and 4.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

10

Start Date

March 2014

Completion Date

December 13, 2019

Primary Completion Date

December 13, 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Female, age 18 and older with clinically definitive diagnosis (biopsy proven or
             compatible chest CT/MRI scan) of sporadic LAM (LAM-S) or LAM associated with TS
             (LAM-TS).

          -  Treated with a stable (at least 3 months) dose of sirolimus or everolimus

          -  Negative pregnancy test (women of child bearing potential) at screening.

          -  Women of childbearing potential must be using barrier, medically acceptable
             contraceptive precautions.

          -  Signed and dated informed consent.

        Exclusion Criteria:

          -  Age < 18 years

          -  Known allergy to simvastatin or currently taking simvastatin, or therapy with a
             medication in the same class as simvastatin within the past 30 days.

          -  Allergy to sirolimus or everolimus.

          -  Current use of other than sirolimus or everolimus investigational drug for TSC or LAM
             within the past 30 days.

          -  Use of estrogen containing medications, including birth control pills, within the 30
             days prior to enrollment.

          -  Treatment with drugs having known metabolic interactions with statin drugs (e.g.
             cytochrome P450 3A4 metabolism), including ketoconazole, itraconazole, fluconazole,
             erythromycin, clarithromycin, azithromycin, niacin (nicotinic acid), digoxin,
             warfarin, sildenafil or use of strong CYP3A4 inhibitors including gemfibrozil,
             cyclosporine, danazol, verapamil, diltiazem, and dronedarone. amiodarone, amlodipine,
             and ranolazine.

          -  Participation in another clinical study(ies) of an investigational treatment or drug
             within 30 days prior to the screening visit.

          -  Amiodarone; within the past 30 days.

          -  Significant dysfunction of liver (ALT > 2 times upper limit of normal-ULN), kidney
             (serum creatinine > 1.5 times ULN), or blood (leucopenia (ANC<2000), anemia, Hgb < 11
             gm/dl).

          -  History of inflammatory muscle disease or myopathy.

          -  Bleeding diathesis or anticoagulant therapy.

          -  Uncontrolled hyperlipidemia or diabetes.

          -  Pregnant, breast feeding, or plan to become pregnant within the next 6 months

          -  Inadequate contraception (must agree to barrier method)

          -  History of organ transplant.

          -  Active on transplant list.

          -  Severe or uncontrolled medical conditions which would cause an unacceptable safety
             risk or compromise compliance with the protocol.

          -  Unstable seizures (recent changes in pattern or anti-epileptics).

          -  Mental illness or cognitive deficit precluding informed consent..

          -  Inability to attend scheduled clinic visits or comply with study procedures.
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Vera P Krymskaya, PhD, MBA, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02061397

Organization ID

The SOS Trial


Responsible Party

Sponsor

Study Sponsor

University of Pennsylvania

Collaborators

 The LAM Foundation

Study Sponsor

Vera P Krymskaya, PhD, MBA, Principal Investigator, University of Pennsylvania


Verification Date

August 2020