Safety of Simvastatin in LAM and TSC (SOS)

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by University of Pennsylvania
Sponsor:
Collaborator:
The LAM Foundation
Information provided by (Responsible Party):
Vera Krymskaya, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT02061397
First received: January 23, 2014
Last updated: March 24, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Lymphangioleiomyomatosis
Tuberous Sclerosis Complex
Drug: Simvastatin
Phase 1
Phase 2

Study Type: Interventional
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)

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 10
Study Start Date: March 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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 (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.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02061397

Contacts
Contact: Vera P Krymskaya, PhD, MBA 215-573-9861 krymskay@mail.med.upenn.edu
Contact: Maryl Kreider, MD, MSCE 215-614-1939 maryl.kreider@uphs.upenn.edu

Locations
United States, Pennsylvania
University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Vera P Krymskaya, PhD, MBA    215-573-9861    krymskay@mail.med.upenn.edu   
Contact: Kelly Morrissy, RN, MSN, MBA    215-615-0276    kelly.morrissey2@uphs.upenn.edu   
Principal Investigator: Vera P Krymskaya, PhD, MBA         
Sub-Investigator: Maryl Kreider, MD, MSCE         
Sponsors and Collaborators
University of Pennsylvania
The LAM Foundation
Investigators
Principal Investigator: Vera P Krymskaya, PhD, MBA University of Pennsylvania
Study Director: Robert Kotloff, MD University of Pennsylvania
Study Director: Maryl Kreider, MD, MSCE University of Pennsylvania
Study Chair: Frank McCormack, MD University of Cincinnati
  More Information

No publications provided

Responsible Party: Vera Krymskaya, Associate Professor of Medicine - Pulmonary, Allergy, Critical Care, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT02061397     History of Changes
Other Study ID Numbers: The SOS Trial
Study First Received: January 23, 2014
Last Updated: March 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
lymphangioleiomyomatosis (LAM)
tuberous sclerosis complex (TSC)
simvastatin
sirolimus
everolimus

Additional relevant MeSH terms:
Sclerosis
Tuberous Sclerosis
Lymphangioleiomyomatosis
Pathologic Processes
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Lymphangiomyoma
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
Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 28, 2014