Multicenter Interventional Lymphangioleiomyomatosis (LAM) Early Disease Trial

Study Purpose

This is a study to determine if early, long-term low dose sirolimus is effective for preventing progression to more advanced stages.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender Female
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Female, age 18 or over 2. Signed and dated informed consent 3. Diagnosis of LAM as determined by compatible lung CT and one of the following 1. biopsy (lung, abdominal mass, lymph node or kidney) or cytology from thoracic or abdominal sources revealing LAM, or 2. tuberous sclerosis, angiomyolipomata (diagnosed by CT, MRI by the site radiologist or biopsy) or chylous pleural effusion (verified by tap), or 3. VEGF-D level ≥ 800 pg/ml. 4. Post-bronchodilator forced expiratory volume in one second of > 70% 5. Presence of markers of non-trivial burden of LAM or likely progression based on one of the following: 1. pretrial FEV 1 rate of decline of >60cc/yr, comparing enrollment FEV1 to any prior measurement in the past 3 years, or 2. baseline supplemental oxygen requirement with exercise, or 3. pre-menopausal and one of the following (if post-menopausal, must have a VEGF-D level ≥ 600 pg/ml and one of the following) baseline diffusing capacity for carbon monoxide ≤80% predicted, a) baseline residual volume ≥120% predicted, b) baseline desaturation by 4% or more on six minute walk testing on room air c) more than 20 cysts on the carinal cut of the CT

Exclusion Criteria:

1. Existing or imminent (within 12-18 months) clinical indication for treatment with mTOR inhibitors, based on judgment of site investigator 2. DLCO <60% predicted 3. Resting room air saturation <90% 4. Exercise induced desaturation nadir on room air < 85% 5. History of myocardial infarction, angina or stroke related to atherosclerosis 6. Pregnant, breast feeding, or plan to become pregnant in the next 2.5 years 7. Inadequate contraception 8. Significant hematologic, renal, metabolic or hepatic abnormality (i.e. transaminase levels > three times the UL of normal range, HCT < 30%, platelets < 80,000/mm3, adjusted absolute neutrophil count < 1,000/ mm3, total WBC < 3,000/ mm3), creatinine >2.5 mg/dl, uncontrolled hyperlipidemia 9. Acute or chronic infection, such as (nontuberculous mucobacteria or active hepatitis B or C infections) 10. Recent surgery (involving entry into a body cavity or requiring 3 or more sutures) within three weeks of initiation of study drug 11. Use of sirolimus, everolimus or investigational treatment for LAM within the 30 days prior to randomization 12. Previous lung transplantation or active on transplant list 13. Inability to attend scheduled clinic visits, or perform pulmonary function testing 14. Pleural effusion or chylous ascites sufficient to affect pulmonary function based on the opinion of the Site Investigator 15. Acute pneumothorax within the past month 16. History of malignancy in the past two years, other than squamous or basal cell skin cancer. 17. Use of estrogen containing medications within the 30 days prior to randomization. 18. Known allergy to sirolimus

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT03150914
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 3
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Cincinnati
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Francis X. McCormack, M.D.
Principal Investigator Affiliation Univerisity of Cincinnati
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

OtherNIHNIHOther
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

LAM, Lymphangioleiomyomatosis
Additional Details

The primary objective of the MILED trial is to determine if early, long term (2 yr), low dose (fixed at 1 mg/day) treatment of patients with well-preserved lung function will prevent disease progression to more advanced stages. Sixty patients with FEV1>70% predicted will be enrolled and randomized to receive 1 mg/day sirolimus or placebo, and followed for a period of 2 years with pulmonary function testing every 4 months. The primary endpoint will be the between-group (placebo vs.#46; sirolimus) difference in the rate of change in FEV1 (in liters) over two years. Secondary endpoints will include severity grade adverse events, time to 200cc or 10% FEV1 decline, forced vital capacity, lung volumes, diffusing capacity, serum VEGF-D, and early airflow obstruction assessed using hyper-polarized gas MRI. The study will be conducted through the Rare Lung Disease Clinic Network, a confederacy of clinics organized by the LAM Foundation that is currently following over 1300 U.S. LAM patients and conducting the Department of Defense sponsored Trial of an Aromatase Inhibitor in LAM (TRAIL) trial. The LAM Foundation will assist with study recruitment and dissemination of results, and the University of South Florida will function as the Data Coordinating Center. Successful completion of this study will define the safety and efficacy of low dose sirolimus in patients with normal lung function, and determine if sirolimus can be used to prevent disease progression to symptomatic stages.

Arms & Interventions

Arms

Placebo Comparator: Placebo

Overencapsulated matrix

Active Comparator: Treatment

Over-encapsulated 1 mg sirolimus tablet

Interventions

Drug: - Sirolimus

mTOR inhibitor or placebo

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

UCLA, Los Angeles, California

Status

Recruiting

Address

UCLA

Los Angeles, California, 90095

Site Contact

Ariss Derhovanessian, MD

aderho@mednet.ucla.edu

310-825-5316

Stanford University, Palo Alto, California

Status

Recruiting

Address

Stanford University

Palo Alto, California, 94305

Site Contact

Stephen Ruoss, M.D.

ruoss@stanford.edu

650-723-6381

National Jewish Hospital, Denver, Colorado

Status

Recruiting

Address

National Jewish Hospital

Denver, Colorado, 80206-2761

Site Contact

Gregory Downey, M.D.

downeyg@njhealth.org

513-558-4376

Emory University, Atlanta, Georgia

Status

Recruiting

Address

Emory University

Atlanta, Georgia, 30322

Site Contact

Srihari Veeraraghavan, MD

veeraraghavan@emory.edu

404-778-5736

Loyola University, Chicago, Illinois

Status

Recruiting

Address

Loyola University

Chicago, Illinois, 60153

Site Contact

Daniel Dilling, M.D.

ddillin@lumc.edu

708-216-4946

Brigham and Woman's Hospital, Boston, Massachusetts

Status

Recruiting

Address

Brigham and Woman's Hospital

Boston, Massachusetts, 20892

Site Contact

Elizabeth P Henske, M.D.

ehenske@bwh.harvard.edu

857-307-0784

Columbia University, New York, New York

Status

Recruiting

Address

Columbia University

New York, New York, 10032

Site Contact

Jeanine D'Armiento, MD

jmd12@columbia.edu

212-305-3745

University of Cincinnati, Cincinnati, Ohio

Status

Recruiting

Address

University of Cincinnati

Cincinnati, Ohio, 45174

Site Contact

Susan McMahan, BSN

susan.mcmahan@uc.edu

513-558-4376

University of Pennsylvania, Philadelphia, Pennsylvania

Status

Recruiting

Address

University of Pennsylvania

Philadelphia, Pennsylvania, 19104

Swedish Health, Seattle, Washington

Status

Recruiting

Address

Swedish Health

Seattle, Washington, 98104

Site Contact

George Pappas, MD

george.pappas@swedish.org

206-469-0264

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