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Trial record 1 of 1 for:    Safety Study of Simvastatin (SOS)
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Safety of Simvastatin in LAM and TSC (SOS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02061397
Recruitment Status : Active, not recruiting
First Posted : February 12, 2014
Last Update Posted : February 6, 2019
The LAM Foundation
Information provided by (Responsible Party):
University of Pennsylvania

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.

Condition or disease Intervention/treatment Phase
Lymphangioleiomyomatosis Tuberous Sclerosis Complex Drug: Simvastatin Phase 1 Phase 2

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The Safety of Simvastatin (SOS) in Patients With Pulmonary Lymphangioleiomyomatosis (LAM) and With Tuberous Sclerosis Complex (TSC)
Study Start Date : March 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Arm Intervention/treatment
Experimental: single simvastatin treatment arm
Simvastatin 20 mg oral daily for 2 months; if tolerated, followed by simvastatin 40 mg oral daily for 2 months
Drug: Simvastatin
Eligible patients 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.
Other Name: trade name Zocor

Primary Outcome Measures :
  1. Safety of simvastatin in the treatment of LAM-S and LAM-TS patients on a stable (for at least 3 months) dose of sirolimus or everolimus. [ Time Frame: 3 months ]
    Safety (including any major changes or deterioration in patient health) will be measure by reductions from baseline in physical examination, pulmonary function tests and/or blood values (CBC, serum chemistry) and in the reporting of new or aggravated adverse events. A Data Safety Monitoring Board will review data, particularly significant and serious adverse events, for trends and recommendations regarding the safe treatment of patients during the study.

Secondary Outcome Measures :
  1. FEV1, FVC, DLCO, VEGF-D, and QOL; signs of clinical benefit. [ Time Frame: 3 months ]
    Pulmonary measures (FEV1, FVC, DLCO), VEGF-D, and QOL; signs of clinical benefit.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02061397

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United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
University of Pennsylvania
The LAM Foundation
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Principal Investigator: Vera P Krymskaya, PhD, MBA University of Pennsylvania
Study Director: Maryl Kreider, MD, MSCE University of Pennsylvania
Study Chair: Frank McCormack, MD University of Cincinnati
Publications of Results:
Other Publications:
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Responsible Party: University of Pennsylvania Identifier: NCT02061397    
Other Study ID Numbers: The SOS Trial
First Posted: February 12, 2014    Key Record Dates
Last Update Posted: February 6, 2019
Last Verified: February 2019
Keywords provided by University of Pennsylvania:
lymphangioleiomyomatosis (LAM)
tuberous sclerosis complex (TSC)
Additional relevant MeSH terms:
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Tuberous Sclerosis
Pathologic Processes
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Perivascular Epithelioid Cell Neoplasms
Neoplasms, Connective and Soft Tissue
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Anticholesteremic Agents
Hypolipidemic Agents