Safety of Simvastatin in LAM and TSC (SOS)
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.
Tuberous Sclerosis Complex
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Safety of Simvastatin (SOS) in Patients With Pulmonary Lymphangioleiomyomatosis (LAM) and With Tuberous Sclerosis Complex (TSC)|
- 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 ] [ Designated as safety issue: No ]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.
- FEV1, FVC, DLCO, VEGF-D, and QOL; signs of clinical benefit. [ Time Frame: 3 months ] [ Designated as safety issue: No ]Pulmonary measures (FEV1, FVC, DLCO), VEGF-D, and QOL; signs of clinical benefit.
|Study Start Date:||March 2014|
|Estimated Study Completion Date:||June 2016|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
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
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
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).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02061397
|Contact: Vera P Krymskaya, PhD, MBAfirstname.lastname@example.org|
|Contact: Maryl Kreider, MD, MSCEemail@example.com|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Vera P Krymskaya, PhD, MBA 215-573-9861 firstname.lastname@example.org|
|Contact: Kelly Morrissy, RN, MSN, MBA 215-615-0276 email@example.com|
|Principal Investigator: Vera P Krymskaya, PhD, MBA|
|Sub-Investigator: Maryl Kreider, MD, MSCE|
|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|