Plain English Summary
Not provided at time of registration
Trial website
http://rarediseasesnetwork.epi.usf.edu/rldc/centers/uhn-toronto.htm
Contact information
Type
Scientific
Primary contact
Dr Gregory Paul Downey
ORCID ID
Contact details
11C-1183
Toronto General Hospital
Toronto
Ontario
M5G 1L7
Canada
+1 416 340 4996
gregory.downey@uhn.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT00414648
Protocol/serial number
MCT-83051
Study information
Scientific title
Sirolimus Multicentre International Lymphangioleiomyomatosis Efficacy and Safety: Canadian component - a placebo-controlled, randomised, parallel group trial
Acronym
MILES
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 Childrens 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
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Condition
Lymphangioleiomyomatosis (LAM)
Intervention
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 lianne.singer@uhn.on.ca for details on this trial (scientific and public queries).
Intervention type
Drug
Phase
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
01/06/2007
Overall trial end date
31/12/2010
Reason abandoned (if study stopped)
Eligibility
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
Patient
Age group
Adult
Gender
Female
Target number of participants
260
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
01/06/2007
Recruitment end date
31/12/2010
Locations
Countries of recruitment
Australia, Canada, Japan, United States of America
Trial participating centre
11C-1183
Toronto, Ontario
M5G 1L7
Canada
Sponsor information
Organisation
University Health Network (Toronto) (Canada)
Sponsor details
200 Elizabeth Street
Toronto
Ontario
M5G 2C4
Canada
Sponsor type
Research organisation
Website
Funders
Funder type
Research organisation
Funder name
Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-83051)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
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: http://www.ncbi.nlm.nih.gov/pubmed/21410393
2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/24159565
Publication citations
-
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.
-
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.