Sirolimus Multicentre International Lymphangioleiomyomatosis Efficacy and Safety trial (the MILES trial): Canadian component

ISRCTN	ISRCTN13402678
DOI	https://doi.org/10.1186/ISRCTN13402678
ClinicalTrials.gov number	NCT00414648
Secondary identifying numbers	MCT-83051

Submission date: 04/02/2008
Registration date: 04/02/2008
Last edited: 29/10/2013

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Cancer

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Dr Gregory Paul Downey
Scientific

11C-1183
Toronto General Hospital
Toronto, Ontario
M5G 1L7
Canada

Phone	+1 416 340 4996
Email	gregory.downey@uhn.on.ca

Study information

Study design	International, multicentre, placebo-controlled, randomised, parallel group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	Sirolimus Multicentre International Lymphangioleiomyomatosis Efficacy and Safety: Canadian component - a placebo-controlled, randomised, parallel group trial
Study acronym	MILES
Study objectives	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(s)	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.
Health condition(s) or problem(s) studied	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
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	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 study start date	01/06/2007
Completion date	31/12/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Female
Target number of participants	260
Key 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
Key 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
Date of first enrolment	01/06/2007
Date of final enrolment	31/12/2010

Locations

Countries of recruitment

Australia
Canada
Japan
United States of America

Study participating centre

11C-1183

Toronto, Ontario
M5G 1L7
Canada

Sponsor information

University Health Network (Toronto) (Canada)
Research organisation

200 Elizabeth Street
Toronto, Ontario
M5G 2C4
Canada

Website	http://www.uhn.ca/index.htm
"ROR"	https://ror.org/042xt5161

Funders

Funder type

Research organisation

Canadian Institutes of Health Research (CIHR) (Canada) - http://www.cihr-irsc.gc.ca (ref: MCT-83051)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	28/04/2011		Yes	No
Results article	results	01/08/2013		Yes	No