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Clinical Studies
5702: Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus Trial (MILES)
Status: recruiting
Investigator Name: Francis X. McCormack, MD
Please Note: The Rare Diseases Clinical Research Network will make every effort to enroll all the patients we can, but we cannot make any guarantees that we will be able to enroll everyone in a particular study who wants to participate.
Rationale for Study: Lymphangioleiomyomatosis (LAM) is an uncommon lung disease that affects women almost exclusively. LAM is associated with mutations in tuberous sclerosis genes, whether it occurs in patients with tuberous sclerosis complex or sporadically in patients without the inherited disease. LAM has an insidious onset, and is typically slowly progressive. Infiltration of the peribronchiolar, perilymphatic, perivascular and alveolar interstitium with atypical smooth muscles cells and cystic destruction of the lung parenchyma are histopathologic hallmarks of the disease. Average survival of patients who present with shortness of breath is thought to range from 8.5-15 years. There are currently no proven therapies for LAM.
Objectives: The objectives of this study are:
1) To assess the safety of sirolimus administered orally with a placebo in patients with LAM.
2) To assess the effect of sirolimus on biological and clinical markers of lung function, including spirometry, dyspnea, quality of life, lung volumes, diffusion, oxygenation, and exercise tolerance.
Study Design: The study design will be a phase III, randomized, double-blind, placebo-controlled study of the safety and clinical effects of sirolimus administered orally to patients with LAM. Study subjects with LAM will be treated with sirolimus 2 mg orally once per day versus a placebo control for a period of 12 months. The study will last two years, and there will be a total of 9 study visits over 2 years.
Number of Patients: 120 patients will be enrolled into the trial in total (60 active drug and 60 placebo).
Population: The study population will consist of female outpatients with LAM 18 years and older. Patients enter the trial as treatment naïve or having failed therapy with anti-hormonal therapies, such as progesterone or lupron.
Inclusion Criteria:
- Aged 18 or over
- Signed and dated informed consent
- Diagnosis of LAM as determined by biopsy; or chest CT scan findings compatible with LAM in the setting of tuberous sclerosis, angiomyolipoma or chylous pleural effusion
- Abnormal lung function (i.e., FEV1 less than or equal to 70% of predicted after inhalation of bronchodilator)
Exclusion Criteria:
- History of myocardial infarction or stroke related to atherosclerosis
- Pregnancy or breast feeding
- Inadequate contraception
- Significant hematologic or hepatic abnormality (i.e., transaminase levels > three times the upper limit of normal range, HCT < 30%, platelets < 80,000/cumm, adjusted absolute neutrophil count < 1,000/cumm total WBC < 3,000/cumm)
- Intercurrent infection at initiation of sirolimus
- Recent surgery (involving entry into a body cavity or requiring sutures) within 2 months of initiation of sirolimus
- Use of an investigational drug within the last 30 days
- Uncontrolled hyperlipidemia
- Previous lung transplantation or active on transplant list
- Inability to attend scheduled clinic visits
- Inability to give informed consent
- Inability to perform pulmonary function testing
- Creatinine > 2.5 mg/dl
- Chylous ascites sufficient to affect diaphragmatic function
- Pleural effusion sufficient to affect pulmonary function
- Acute pneumothorax within the past 2 months
- History of malignancy in past 2 years other than squamous or basil cell skin cancer
- Use of medications containing estrogen
- Allergy to sirolimus
Treatment regimen: The treatment regimen will consist of 2 mg of sirolimus or placebo orally once per day for a period of 12 months.
Study Duration/Timelines: Patient accrual will occur over a period of 30 months. The starting date for the study will be the late December of 2006 and the study will conclude in the spring of 2011. Publication would be expected in late 2011.
Primary Endpoint: FEV1 response at 6 months, 12 months and 24 months
Efficacy: Efficacy will also be judged by the following secondary endpoints:
- FVC response at 6 months, 12 months, and 24 months
- Lung volume response at 12 months, and 24 months
- DLCO response at 24 months
- Aa gradient response at 24 months
- Six-minute walk distance at 12 months and 24 months
- Dyspnea and Quality of Life at 12 months and 24 months
How to Participate:
In order to participate in a study, you must personally contact the study coordinator of any of the participating institutions by phone or by e-mail. Please use the information below to inquire about participation.
- University of Cincinnati Medical Center, Cincinnati, Ohio
Leslie Korbee
Project Manager
513-636-1891
E-mail: Leslie.Korbee@cchmc.org
- Medical University of South Carolina (MUSC), Charleston, SC
Amie Gitter, RN
843-792-6569
E-mail: gitterac@musc.edu
- Oregon Health & Science University, Portland, OR
Karlene Kennie
503-494-1305
E-mail: kenniek@ohsu.edu
- Cleveland Clinic Foundation, Cleveland, OH
Diane Faile
216-444-9975
E-mail: failed@ccf.org
- National Jewish Medical & Research Center, Denver, Colorado
Marianne Morrison, RRT, C-PFT, CCRC
303-270-2053
E-mail: morrisonm@njc.org
- University of Florida Medical Center, Gainesville, FL
Pam Schreck, RN, MSN,
352-294-0512
E-mail: pschreck@ufl.edu
- National Kinki-Chou Hospital, Osaka, Japan
Kazuhiro Hirohata
+81-72-252-1313
E-mail: crc@kch.hosp.go.jp
- Niigata University Medical & Dental Hospital, Niigata, Japan
Chinatsu Kaneko
+81 (25) 227-2022
E-mail: kanekochinatsu@bmrc.jp
- National Heart, Lung, and Blood Institute (National Institutes of Health), Bethesda, MD
Mary Haughey
301-496-3632
E-mail: mhaughey@nhlbi.nih.gov
- University of California Los Angeles, Los Angeles, CA
Michaela Dyke
310-794-3299
E-mail: mdyke@mednet.ucla.edu
Eileen Callahan
310-794-2466
E-mail: ecallahan@mednet.ucla.edu
- University of Toronto/Toronto General Hospital, Toronto, Ontario, Canada
Mihaiela Sichitiu
416-340-4800 ext.2021
E-mail: msichiti@uhnres.utoronto.ca
- University of Texas Health Center, Tyler, TX
Jan Hoeft, RN
903-877-5518
E-mail: janice.hoeft@uthct.edu
- Harvard/Brigham & Women's Hospital, Boston, MA
Betsy Peters, BSN, RN
617-525-9331
E-mail: epeters2@partners.org
Join the Contact Registry for: Lymphangioleiomyomatosis (LAM)
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