Safety of Simvastatin in LAM and TSC (SOS)

August 12, 2020 updated by: University of Pennsylvania

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: simvastatin treatment arm
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: 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.
Other Names:
  • trade name Zocor
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.
Other Names:
  • Rapamune
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.
Other Names:
  • Afinitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of Simvastatin in the Treatment of LAM-S and LAM-TS Patients
Time Frame: 5 months
Safety is a primary outcome measure which will be assessed by any major changes or deterioration in patient health.
5 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Predicted FEV1
Time Frame: 5 months
Lung function will be measured by FEV1: forced expiratory volume in 1s mean and calculated as % predicted +_ SD (standard deviation).
5 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Pennsylvania

Collaborators

The LAM Foundation

Investigators

  • 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 and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2014

Primary Completion (ACTUAL)

December 13, 2019

Study Completion (ACTUAL)

December 13, 2019

Study Registration Dates

First Submitted

January 23, 2014

First Submitted That Met QC Criteria

February 10, 2014

First Posted (ESTIMATE)

February 12, 2014

Study Record Updates

Last Update Posted (ACTUAL)

August 25, 2020

Last Update Submitted That Met QC Criteria

August 12, 2020

Last Verified

August 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • The SOS Trial

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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