Safety of Simvastatin in LAM and TSC

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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


Primary Outcome

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

Secondary Outcome

 Percent Predicted FEV1





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.


* 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


Estimated Enrollment


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

          -  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

          -  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.




18 Years - N/A

Accepts Healthy Volunteers



Vera P Krymskaya, PhD, MBA, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID

The SOS Trial

Responsible Party


Study Sponsor

University of Pennsylvania


 The LAM Foundation

Study Sponsor

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

Verification Date

August 2020