Protocol Number: 08-H-0177

Title:

Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus Trial (The MILES Trial)

Number:

08-H-0177

Summary:

This study will examine whether sirolimus, a drug that suppresses the immune system, can improve lung function in people with lymphangioleiomyomatosis (LAM). LAM is a lung disease in which unusual muscle cells growing inside the lungs prevent them from working properly over time.

Women 18 years of age or older with lymphangioleiomyomatosis (LAM) may be eligible for this study.

Participants are randomly assigned to receive either sirolimus or placebo. Both groups take two tablets every day, and both groups may have the number of tablets adjusted based on blood tests. In addition to taking a study drug or placebo, patients have study visits at enrollment, 3 weeks after enrollment, then once every 3 months in the first year and once every 6 months in the second year. The visits include the following:

Physical examination, blood tests and questionnaires relating to the patient's lung health and general health every visit.

Spirometry test to measure lung function every 3 months the first year and every 6 months the second year. For this test, the subject inhales deeply and then blows through a mouthpiece into a tube as fast as she can until the air is exhaled. The test is repeated after the subject takes a bronchodilator medicine (salbutamol/albuterol).

At six of the visits, additional pulmonary function tests are done to measure lung volumes (how much air is in the chest) and how well oxygen passes from the air sacs of the lungs into the blood. These tests require the subject to take additional breaths in and out of the mouthpiece.

At six of the visits, subjects perform a 6-minute walk test on room air or on oxygen in order to test exercise tolerance. The subject walks for 6 minutes while oxygen saturation, heart rate, and the distance walked are measured.

Chest x-rays: Chest x-rays are done at the first and last visits to compare lung damage from disease.

Volumetric chest CT scan: This scan is done at three visits to measure the amount of normal tissue in the chest and the portion of the lungs involved with cysts.

Urine tests for pregnancy at each visit and for kidney function.

Drug diaries: Subjects keep a record of all the medicines, including the study drug, that they take while on the study.

Sponsoring Institute:

National Heart, Lung and Blood Institute (NHLBI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Female

Referral Letter Required: No

Population Exclusion(s): Male

Children

Eligibility Criteria:

INCLUSION CRITERIA:

a. Female, age 18 or over

b. Signed and dated informed consent

c. Diagnosis of LAM as determined by 1) biopsy (lung, abdominal mass, lymph node or kidney), and chest CT scan findings compatible with LAM; or 2) compatible chest CT scan findings in the setting of tuberous sclerosis, angiomyolipomata (diagnosed by CT, MRI or biopsy) or chylous pleural effusion (verified by tap)

d. Post-bronchodilator forced expiratory volume in one second of less than or equal to 70% of predicted during baseline visit.

EXCLUSION CRITERIA:

a. History of myocardial infarction, angina or stroke related to atherosclerosis

b. Pregnant, breast feeding, or plan to become pregnant within the next 2 years

c. Inadequate contraception

d. Significant hematologic or hepatic abnormality (i.e. transaminase levels greater than three times the upper limit of normal range, HCT less than 30%, platelets less than 80,000/cumm, adjusted absolute neutrophil count less than 1,000/cumm, total WBC less than 3,000/cumm)

e. Intercurrent infection at initiation of study drug

f. Recent surgery (involving entry into a body cavity or requiring sutures) within 2 months of initiation of study drug

g. Use of an investigational drug within the last 30 days

h. Uncontrolled hyperlipidemia

i. Previous lung transplantation or active on transplant list

j. Inability to attend scheduled clinic visits

k. Inability to give informed consent

l. Inability to perform pulmonary function testing

m. Creatinine greater than 2.5 mg/dl.

n. Chylous ascites sufficient to affect diaphragmatic function based on the opinion of the site investigator

o. Pleural effusion sufficient to affect pulmonary function based on the opinion of the Site Investigator (generally greater than 500cc)

p. Acute pneumothorax within the past 2 months

q. History of malignancy in the past two years, other than squamous or basal cell skin cancer.

r. Use of estrogen containing medications

s. Known allergy to sirolimus

Special Instructions:

Currently Not Provided

Keywords:

Sirolimus

Lymphangioleiomyomatosis

Tuberous Sclerosis Complex (TSC)

Recruitment Keyword(s):

Lymphangioleiomyomatosis

LAM

Tuberous Sclerosis

Condition(s):

Lymphangioleiomyomatosis

Tuberous Sclerosis

Investigational Drug(s):

Sirolimus

Investigational Device(s):

None

Intervention(s):

Drug: Sirolimus

Supporting Site:

National Heart, Lung, and Blood Institute

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Sullivan EJ. Lymphangioleiomyomatosis: a review. Chest. 1998 Dec;114(6):1689-703. Review. No abstract available.

Johnson SR, Tattersfield AE. Decline in lung function in lymphangioleiomyomatosis: relation to menopause and progesterone treatment. Am J Respir Crit Care Med. 1999 Aug;160(2):628-33.

Nine JS, Yousem SA, Paradis IL, Keenan R, Griffith BP. Lymphangioleiomyomatosis: recurrence after lung transplantation. J Heart Lung Transplant. 1994 Jul-Aug;13(4):714-9.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

National Institutes of Health Clinical Center Bethesda, Maryland 20892. Last update: 01/13/2009