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LymphangioleiomyomatosisPhase 1/2SOSNCT02061397

Safety of Simvastatin in LAM and TSC

A Phase 1/2 study testing Simvastatin, Sirolimus Oral Product and Everolimus Oral Product in people with Lymphangioleiomyomatosis and Tuberous Sclerosis Complex, run by University of Pennsylvania at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Simvastatin, Sirolimus Oral Product and Everolimus Oral Product
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
Mar 2014to 13 Dec 2019
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

Other trials in United States

About this study

Official title: 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.

Read more

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.
Read the 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).

Being tested
Simvastatin, Sirolimus Oral Product, Everolimus Oral Product
Keywords
lymphangioleiomyomatosis (LAM), tuberous sclerosis complex (TSC), simvastatin, sirolimus, everolimus
Medical subject headings
Lymphangioleiomyomatosis, Tuberous Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SimvastatinDrug

    Also called trade name Zocor

    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.

  • Sirolimus Oral ProductDrug

    Also called Rapamune

    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.

  • Everolimus Oral ProductDrug

    Also called Afinitor

    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.

Study groups in NCT02061397
Study groupRoleWhat they receive
simvastatin treatment armExperimentalEligible 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.
Receives: Drug: Simvastatin; Drug: Sirolimus Oral Product; Drug: Everolimus Oral Product

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety of Simvastatin in the Treatment of LAM-S and LAM-TS Patients

    Safety is a primary outcome measure which will be assessed by any major changes or deterioration in patient health.

    Measured: 5 months

Secondary outcomes (1)

  1. Percent Predicted FEV1

    Lung function will be measured by FEV1: forced expiratory volume in 1s mean and calculated as % predicted +_ SD (standard deviation).

    Measured: 5 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Feb 2014 (estimated)
  2. Study startMar 2014
  3. Primary completion13 Dec 2019
  4. Study completion13 Dec 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02061397
Sponsor's protocol ID
The SOS Trial
Acronym
SOS
Status last verified
Aug 2020
First submitted
23 Jan 2014
Last updated
25 Aug 2020
Data monitoring committee
Yes

Publications

  • Krymskaya VP. Treatment option(s) for pulmonary lymphangioleiomyomatosis: progress and current challenges. Am J Respir Cell Mol Biol. 2012 May;46(5):563-5. doi: 10.1165/rcmb.2011-0381ED. No abstract available.

    PubMed 22550272

  • Goncharova EA, Goncharov DA, Fehrenbach M, Khavin I, Ducka B, Hino O, Colby TV, Merrilees MJ, Haczku A, Albelda SM, Krymskaya VP. Prevention of alveolar destruction and airspace enlargement in a mouse model of pulmonary lymphangioleiomyomatosis (LAM). Sci Transl Med. 2012 Oct 3;4(154):154ra134. doi: 10.1126/scitranslmed.3003840.

    PubMed 23035046

  • Atochina-Vasserman EN, Goncharov DA, Volgina AV, Milavec M, James ML, Krymskaya VP. Statins in lymphangioleiomyomatosis. Simvastatin and atorvastatin induce differential effects on tuberous sclerosis complex 2-null cell growth and signaling. Am J Respir Cell Mol Biol. 2013 Nov;49(5):704-9. doi: 10.1165/rcmb.2013-0203RC.

    PubMed 23947572

  • Goncharova EA, Goncharov DA, Li H, Pimtong W, Lu S, Khavin I, Krymskaya VP. mTORC2 is required for proliferation and survival of TSC2-null cells. Mol Cell Biol. 2011 Jun;31(12):2484-98. doi: 10.1128/MCB.01061-10. Epub 2011 Apr 11.

    PubMed 21482669

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Simvastatin, Sirolimus Oral Product and Everolimus Oral Product in people with Lymphangioleiomyomatosis and Tuberous Sclerosis Complex, run by University of Pennsylvania at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 25 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Aug 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Simvastatin in the Treatment of LAM-S and LAM-TS Patients (time frame: 5 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02061397, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2020.

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