Safety of Simvastatin in LAM and TSC

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.

Conditions

• Lymphangioleiomyomatosis
• Tuberous Sclerosis Complex

Interventions

DRUG

Simvastatin

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.

DRUG

Sirolimus Oral Product

Eligible patients on sirolimus 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.

DRUG

Everolimus Oral Product

Eligible patients on 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.

Sponsors & Collaborators

• The LAM Foundation

  collaborator OTHER

• University of Pennsylvania

  lead OTHER

Principal Investigators

• Vera P Krymskaya, PhD, MBA · University of Pennsylvania

• Maryl Kreider, MD, MSCE · University of Pennsylvania

• Frank McCormack, MD · University of Cincinnati

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-03-31

Primary Completion

2019-12-13

Completion

2019-12-13

Countries

• United States

Study Locations