Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Gregory Paul Downey


Contact details

Toronto General Hospital
M5G 1L7
+1 416 340 4996

Additional identifiers

EudraCT number number


Protocol/serial number


Study information

Scientific title

Sirolimus Multicentre International Lymphangioleiomyomatosis Efficacy and Safety: Canadian component - a placebo-controlled, randomised, parallel group trial



Study hypothesis

1. Implement a double-blind, placebo-controlled, 'intention to treat' based, multicentre protocol for the determination of the safety and efficacy of sirolimus in patients with lymphangioleiomyomatosis (LAM)
2. Determine the correlation between changes in lung function and questionnaire-based assessments of dyspnoea, quality of life, fatigue, and degree of health impairment in LAM trial patients who are taking sirolimus or placebo

Ethics approval

1. Research Ethics Board of University Health Network, Toronto (Canada) approved on 07/12/2007 (ref: 07-095-A)
2. Institutional Review Board of Niigata University Medical and Dental Hospital (Japan) approved on the 24/07/2007 (ref: NH19-003)
3. Institutional Review Board (Federalwide Assurance # 00002988) of Cincinnati Children’s Hospital Medical Center, Cincinnati (USA) approved on 11/01/2008 (ref: 04-11-17)

Ethics approval from Australia pending.

Study design

International, multicentre, placebo-controlled, randomised, parallel group trial

Primary study design


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet


Lymphangioleiomyomatosis (LAM)


This is a multicentre, international, intention to treat, placebo-controlled, randomised parallel, drug/diagnostic, efficacy and safety trial with study participant, study investigator, caregiver, outcome assessor, and data analyst blinded.

1. Experimental group: sirolimus (rapamycin), daily dose of 2 mg during 12 months; follow up only for additional 12 months
2. Control group: matching placebo of active treatment, 1 pill daily for 12 months; follow up only for additional 12 months

Contact for public queries same as below. Please note that you can also contact Dr
Lianne Singer at for details on this trial (scientific and public queries).

Intervention type



Not Applicable

Drug names

Sirolimus (rapamycin)

Primary outcome measure

FEV1 slope response, measured at 12 months.

Secondary outcome measures

Measured at 12 months:
1. Six minute walk testing
2. Quantitative CT of the lung
3. Quality of life questionnaires (St George Respiratory Questionnaire, 36-item short form health survey [SF-36])
4. Forced vital capacity (FVC)
5. Diffusing capacity of the lung for carbon monoxide (DLCO)

Overall trial start date


Overall trial end date


Reason abandoned (if study stopped)


Participant inclusion criteria

1. Women, aged 18 years and older
2. Signed and dated informed consent
3. Diagnosis of LAM as determined by biopsy (lung, abdominal mass, lymph node or kidney) and chest computed tomography [CT] scan findings compatible with LAM; or compatible chest CT scan findings in the setting of tuberous sclerosis, angiomyolipomata (diagnosed by CT, magnetic resonance imaging [MRI] or biopsy), or chylous pleural effusion (verified by thoracentesis)
4. Forced expiratory volume in one second (FEV1) less than or equal to 70% of predicted during baseline visit after bronchodilator

Participant type


Age group




Target number of participants


Participant exclusion criteria

1. History of myocardial infarction, angina or stroke related to atherosclerosis
2. Pregnancy or breast feeding, inadequate contraception
3. Significant haematologic or hepatic abnormality (i.e., transaminase levels greater than 3 times the upper limit of normal range, haematocrit [HCT] less than 30%, platelets less than 80,000/cumm, adjusted absolute neutrophil count less than 1,000/cumm, total white blood cell count [WBC] less than 3,000/cumm)
4. Intercurrent infection at initiation of sirolimus
5. Recent surgery 2 months (involving entry into a body cavity or requiring sutures)
6. Use of an investigational drug within the last 30 days
7. Uncontrolled hyperlipidaemia
8. Previous lung transplantation
9. Inability to attend scheduled clinic visits
10. Inability to give informed consent
11. Inability to perform pulmonary function testing
12. Creatinine greater than 2.5 mg/dl (greater than 220 µmol/L)
13. Chylous ascites sufficient to affect diaphragmatic function on pulmonary function tests (PFTs)
14. Pleural effusion sufficient to affect pulmonary function based on the opinion of the Site Investigator (generally greater than 500 cc)
15. Acute pneumothorax within the past 2 months (as pneumothorax can alter baseline PFT results)
16. History of malignancy in the past two years, other than squamous or basal cell skin cancer
17. Use of oestrogen containing medications

Recruitment start date


Recruitment end date



Countries of recruitment

Australia, Canada, Japan, United States of America

Trial participating centre

Toronto, Ontario
M5G 1L7

Sponsor information


University Health Network (Toronto) (Canada)

Sponsor details

200 Elizabeth Street
M5G 2C4

Sponsor type

Research organisation



Funder type

Research organisation

Funder name

Canadian Institutes of Health Research (CIHR) (Canada) - (ref: MCT-83051)

Alternative name(s)

Funding Body Type

Funding Body Subtype


Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Basic results (scientific)

Publication list

2011 results in:
2013 results in:

Publication citations

  1. Results

    McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Young LR, Kinder BW, Downey GP, Sullivan EJ, Colby TV, McKay RT, Cohen MM, Korbee L, Taveira-DaSilva AM, Lee HS, Krischer JP, Trapnell BC, , , Efficacy and safety of sirolimus in lymphangioleiomyomatosis., N. Engl. J. Med., 2011, 364, 17, 1595-1606, doi: 10.1056/NEJMoa1100391.

  2. Results

    Young L, Lee HS, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX, , Serum VEGF-D a concentration as a biomarker of lymphangioleiomyomatosis severity and treatment response: a prospective analysis of the Multicenter International Lymphangioleiomyomatosis Efficacy of Sirolimus (MILES) trial., Lancet Respir Med, 2013, 1, 6, 445-452, doi: 10.1016/S2213-2600(13)70090-0.

Additional files

Editorial Notes