LymphangioleiomyomatosisPhase 3MILESNCT00414648
Efficacy and Safety of Sirolimus in LAM
A Phase 3 study testing Sirolimus in people with Lymphangioleiomyomatosis, run by University of Cincinnati at 13 sites in 3 countries.
Trial summary
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is caused by genetic mutations. It results in the uncontrolled growth of an unusual type of smooth muscle cell in the lung. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Lymphangioleiomyomatosis
- What is being tested?
- Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 89 participants
- Where
- 13 sitesin 3 countries
- Study dates
- Dec 2006to Feb 2011
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older
- Signed and dated informed consent
- Diagnosis of LAM based on compatible chest CT scan and a) biopsy or cytology consistent with LAM, or b) presence of tuberous sclerosis, angiomyolipoma or chylous pleural effusion; or c) a VEGF-D level of at least 800 pg/ml
- Forced expiratory volume in one second (FEV1) of 70% or less of predicted value after administration of a bronchodilator
Who cannot join
- Known allergy to sirolimus
- History of heart attack, angina, or stroke due to clogging, narrowing, and hardening of the arteries and blood vessels
- Significant hematologic or hepatic abnormality (transaminase levels greater than three times the upper limit of normal, HCT less than 30%, platelets less than 80,000/cubic mm, adjusted absolute neutrophil count less than 1,000/cubic mm, total white blood cell count less than 3,000/cubic mm)
- Intercurrent infection at the time treatment with sirolimus begins
- Any surgery involving entry into a body cavity or requiring three or more sutures within 8 weeks of initiation of study drug
- Use of an investigational drug within the 30 days prior to random assignment
Show all 18Show fewer
- Uncontrolled hyperlipidemia
- Previous lung transplant or currently on lung transplant list
- Unable to attend scheduled study visits
- Unable to perform pulmonary function tests
- Creatinine levels greater than 2.5 mg/dl
- Chylous ascites severe enough to affect diaphragmatic function
- Pleural effusion severe enough to affect pulmonary function, as determined by the study physician
- History of acute pneumothorax within the 2 months prior to study entry
- History of malignancy within the 2 years prior to study entry (except for squamous or basal cell skin cancer)
- Use of estrogen containing medication within the thirty days prior to randomization
- Unable or unwilling to use adequate contraception
- Pregnant, breastfeeding, or plans to become pregnant within the next 2 years
Trial locations and contacts
13 sites in 3 countries.
13 sites in 3 countries
United States10 sites
National Heart, Lung, and Blood Institute
Bethesda, Maryland, 20892
Harvard's Brigham and Women's Hospital
Boston, Massachusetts, 02115
Medical University of South Carolina
Charleston, South Carolina, 29425
University of Cincinnati Medical Center
Cincinnati, Ohio, 45267
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
National Jewish Medical and Research Center
Denver, Colorado, 80206
University of Florida, Gainesville
Gainesville, Florida, 32611
University of California Los Angeles
Los Angeles, California, 90024
Oregon Health & Science University
Portland, Oregon, 97239
University of Texas Health Center at Tyler
Tyler, Texas, 75708
Japan2 sites
Niigata University Medical and Dental Hospital
Niigata
National Kinki-Chou Hospital
Sakai, Osaka, 591-8555
About this study
Official title: Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus Trial
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is caused by genetic mutations. It results in the uncontrolled growth of an unusual type of smooth muscle cell in the lung. These cells invade lung tissue, including the airways, blood vessels, and lymph vessels, and restrict the flow of air, blood, and lymph, respectively. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and effectiveness of sirolimus, an inhibitor of the mTOR pathway, in stabilizing or improving lung function in people with LAM.
Read the detailed description
LAM is an uncommon, progressive, cystic lung disease that predominantly affects young women. The disease is caused by mutations in tuberous sclerosis complex (TSC) genes, which regulate cellular pathways that control nutrient sensing, cell size, cell migration, and cell proliferation. Individuals with LAM often experience pneumothorax and chylothorax, as well progressive loss of lung function. Sirolimus is drug that was approved for the prevention of kidney transplant rejection. It directly affects the cellular pathway that causes LAM. This study will evaluate the safety and effectiveness of sirolimus in stabilizing or improving lung function in people with LAM.
Individuals interested in participating in this 2-year, double-blind study will first report to the study sites for pulmonary function testing to determine their eligibility for participation. Participants deemed eligible will be randomly assigned to receive either sirolimus or placebo for 1 year. Sirolimus or placebo will be administered in 2 tablet doses (2 mg for sirolimus) for the duration of the study. Study visits will occur at baseline, Week 3, every 3 months for 12 months, and months 18 and 24. Study visits will include a physical exam, questionnaires, a pregnancy test, blood and urine collection, and functional lung tests. A 6-minute walk test will occur at most study visits; a chest x-ray will be taken at baseline and month 24; and a volumetric computed tomography scan will occur at baseline, month 12, and month 24. Adverse events, medication side effects, and lung function will be assessed at each visit.
- Conditions
- Lymphangioleiomyomatosis
- Being tested
- Sirolimus, Placebo
- Keywords
- Lymphangiomyomatosis, mTOR
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SirolimusDrug
Also called Rapamycin
A sirolimus dose of 2 tablets (1 mg/tablet) per day for 1 year.
PlaceboDrug
Also called Other names: placebo
A placebo dose of 2 tablets per day for 1 year.
| Study group | Role | What they receive |
|---|---|---|
| Active Agent (Sirolimus) | Experimental | Participants receive sirolimus daily for 1 year and are followed with serial pulmonary function tests, 6-minute walk tests, and symptom and QOL questionnaires over a 2-year period. Receives: Drug: Sirolimus |
| Placebo Arm | Placebo comparator | Participants receive placebo daily for 1 year and followed with serial pulmonary function tests, 6-minute walk tests, and symptom and QOL questionnaires over a 2-year period. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Forced Expiratory Volume in One-second (FEV1) Slope in Milliliters Per Month
FEV1 values reported are in liters or milliliters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. Normative ranges are determined in populations stratified by gender, height, age and race/ethnicity. Higher FEV1 values indicate better lung function.
Measured: Baseline to Month 12
Secondary outcomes (6)
Percent of Participants With Serious Adverse Events
Measured: Baseline to Month 12
Changes in FVC Slope in ml/Month
FVC values are reported in liters or milliliters. Normative ranges are determined in populations that are stratified by gender, height, age and race/ethnicity. There are no minimum or maximum values as it is a physiologic measure of lung function and varies from individual to individual. Higher FVC scores indicate better lung function.
Measured: Baseline to Month 12
Rate of Change in Diffusing Capacity for Carbon Monoxide (DLCO) in ml/Min/mmHg
Diffusing capacity for carbon monoxide is abbreviated DLCO. DLCO is measured in liters and milliliters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. A lower DLCO means that there is lower lung function.
Measured: Baseline to Month 12
Rate of Change in Total Lung Volume in ml Per Month
There are two methods for measurement of total lung volume, nitrogen or helium wash out (total lung capacity or TLC), or plethysmography (Total gas volume or TGV). TLC or TGV is measured in milliliters or liters. Normative ranges for TLC or TGV are stratified by age, height, and sex in population based studies of normal subjects.. There are no definite minimum and maximum values of lung volume as it is a physiological measure of lung function and varies from individual to individual. A low TGV or TLC is suggestive of a restrictive lung disease, and a high TGV or TLC is consistent with obstructive lung disease with hyperinflation.
Measured: Baseline to Month 12
Rate of Change in Six Minute Walk Distance in Meters/Month
Number of meters walked in six minutes. There is no minimum or maximum number of feet walked as this varies from individual to individual. A higher number of feet walked indicates better exercise tolerance
Measured: Baseline to Month 12
Rate of Change in Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels in pg/ml Per Month
Serum VEGF-D is a protein produced by LAM cells that serves as a biomarker of mTOR activation and sirolimus response. Mean serum levels of VEGF-D in normal subjects are around 350 pg/ml. Higher levels of serum VEGF-D are correlated with greater degrees of mTOR activation, and a fall in VEGF-D levels suggest suppression of the mTOR axis.
Measured: Baseline to Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2006 (estimated)
- Study startDec 2006
- Primary completionSep 2010
- Study completionFeb 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for LymphangioleiomyomatosisStudies of the same condition, open and under way.
- More trials run by University of CincinnatiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 89 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- Office of Rare Diseases (ORD), FDA Office of Orphan Products Development, National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, Francis McCormack, University of Cincinnati
- Investigators
- Francis X McCormack, MD, Principal investigator, University of Cincinnati Medical Center Division of Pulmonary and Critical Care Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00414648
- Sponsor's protocol ID
- RDCRN 5702
- Other IDs
- U54RR019498-01, FD-003362-01
- Acronym
- MILES
- Status last verified
- Oct 2023
- First submitted
- 20 Dec 2006
- Last updated
- 2 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- No
Publications
McCarthy C, Gupta N, Johnson SR, Yu JJ, McCormack FX. Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management. Lancet Respir Med. 2021 Nov;9(11):1313-1327. doi: 10.1016/S2213-2600(21)00228-9. Epub 2021 Aug 27.
PubMed 34461049Gupta N, Lee HS, Ryu JH, Taveira-DaSilva AM, Beck GJ, Lee JC, McCarthy K, Finlay GA, Brown KK, Ruoss SJ, Avila NA, Moss J, McCormack FX; NHLBI LAM Registry Group. The NHLBI LAM Registry: Prognostic Physiologic and Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal Analysis. Chest. 2019 Feb;155(2):288-296. doi: 10.1016/j.chest.2018.06.016. Epub 2018 Jun 22.
PubMed 29940164Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, Finlay GA, Olson EJ, Ruoss SJ, Maurer JR, Raffin TA, Peavy HH, McCarthy K, Taveira-Dasilva A, McCormack FX, Avila NA, Decastro RM, Jacobs SS, Stylianou M, Fanburg BL; NHLBI LAM Registry Group. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. 2006 Jan 1;173(1):105-11. doi: 10.1164/rccm.200409-1298OC. Epub 2005 Oct 6.
PubMed 16210669Gupta N, Finlay GA, Kotloff RM, Strange C, Wilson KC, Young LR, Taveira-DaSilva AM, Johnson SR, Cottin V, Sahn SA, Ryu JH, Seyama K, Inoue Y, Downey GP, Han MK, Colby TV, Wikenheiser-Brokamp KA, Meyer CA, Smith K, Moss J, McCormack FX; ATS Assembly on Clinical Problems. Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2017 Nov 15;196(10):1337-1348. doi: 10.1164/rccm.201709-1965ST.
PubMed 29140122McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow CG, Steagall WK, Johnson SR, Sahn SA, Ryu JH, Strange C, Seyama K, Sullivan EJ, Kotloff RM, Downey GP, Chapman JT, Han MK, D'Armiento JM, Inoue Y, Henske EP, Bissler JJ, Colby TV, Kinder BW, Wikenheiser-Brokamp KA, Brown KK, Cordier JF, Meyer C, Cottin V, Brozek JL, Smith K, Wilson KC, Moss J; ATS/JRS Committee on Lymphangioleiomyomatosis. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016 Sep 15;194(6):748-61. doi: 10.1164/rccm.201607-1384ST.
PubMed 27628078McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, 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; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.
PubMed 21410393Argula RG, Kokosi M, Lo P, Kim HJ, Ravenel JG, Meyer C, Goldin J, Lee HS, Strange C, McCormack FX; MILES Study Investigators. A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis. Ann Am Thorac Soc. 2016 Mar;13(3):342-9. doi: 10.1513/AnnalsATS.201509-631OC.
PubMed 26799509Gupta N, Lee HS, Young LR, Strange C, Moss J, Singer LG, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Downey GP, Taveira-DaSilva AM, Krischer JP, Setchell K, Trapnell BC, Inoue Y, McCormack FX; NIH Rare Lung Disease Consortium. Analysis of the MILES cohort reveals determinants of disease progression and treatment response in lymphangioleiomyomatosis. Eur Respir J. 2019 Apr 4;53(4):1802066. doi: 10.1183/13993003.02066-2018. Print 2019 Apr.
PubMed 30846465Young 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 3rd, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX; MILES Trial Group. 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 Aug;1(6):445-52. doi: 10.1016/S2213-2600(13)70090-0.
PubMed 24159565Lo P, Brown MS, Kim H, Kim H, Argula R, Strange C, Goldin JG. Cyst-based measurements for assessing lymphangioleiomyomatosis in computed tomography. Med Phys. 2015 May;42(5):2287-95. doi: 10.1118/1.4916655.
PubMed 25979023Harun N, Gupta N, McCormack FX, Macaluso M. Dynamic use of historical controls in clinical trials for rare disease research: A re-evaluation of the MILES trial. Clin Trials. 2023 Jun;20(3):223-234. doi: 10.1177/17407745231158906. Epub 2023 Mar 17.
PubMed 36927115Xu KF, Wang L, Tian XL, Gui YS, Peng M, Cai BQ, Zhu YJ. The St. George's Respiratory Questionnaire in lymphangioleiomyomatosis. Chin Med Sci J. 2010 Sep;25(3):140-5. doi: 10.1016/s1001-9294(10)60038-7.
PubMed 21180274
Study at a glance
From the registry record, last updated by the sponsor on 2 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus Trial
- ClinicalTrials.gov ID
- NCT00414648
- Acronym / sponsor ID
- MILES / RDCRN 5702
- Conditions
- Lymphangioleiomyomatosis
- Keywords
- Lymphangiomyomatosis, mTOR
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 89 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- Office of Rare Diseases (ORD), FDA Office of Orphan Products Development, National Center for Research Resources (NCRR)
- Study start
- Dec 2006
- Primary completion
- Sep 2010 (actual)
- Study completion
- Feb 2011 (actual)
- First posted
- 21 Dec 2006 (estimated)
- Results
- Posted 2 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Lymphangioleiomyomatosis (LAM) is a rare lung disease of women that is caused by genetic mutations. It results in the uncontrolled growth of an unusual type of smooth muscle cell in the lung. These cells invade lung tissue, including the airways, blood vessels, and lymph vessels, and restrict the flow of air, blood, and lymph, respectively. Respiratory failure, lung collapse (pneumothorax), and pleural effusions (chylothorax) are hallmarks of the disease. This study will evaluate the safety and effectiveness of sirolimus, an inhibitor of the mTOR pathway, in stabilizing or improving lung function in people with LAM.
Detailed description
LAM is an uncommon, progressive, cystic lung disease that predominantly affects young women. The disease is caused by mutations in tuberous sclerosis complex (TSC) genes, which regulate cellular pathways that control nutrient sensing, cell size, cell migration, and cell proliferation. Individuals with LAM often experience pneumothorax and chylothorax, as well progressive loss of lung function. Sirolimus is drug that was approved for the prevention of kidney transplant rejection. It directly affects the cellular pathway that causes LAM. This study will evaluate the safety and effectiveness of sirolimus in stabilizing or improving lung function in people with LAM.
Individuals interested in participating in this 2-year, double-blind study will first report to the study sites for pulmonary function testing to determine their eligibility for participation. Participants deemed eligible will be randomly assigned to receive either sirolimus or placebo for 1 year. Sirolimus or placebo will be administered in 2 tablet doses (2 mg for sirolimus) for the duration of the study. Study visits will occur at baseline, Week 3, every 3 months for 12 months, and months 18 and 24. Study visits will include a physical exam, questionnaires, a pregnancy test, blood and urine collection, and functional lung tests. A 6-minute walk test will occur at most study visits; a chest x-ray will be taken at baseline and month 24; and a volumetric computed tomography scan will occur at baseline, month 12, and month 24. Adverse events, medication side effects, and lung function will be assessed at each visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active Agent (Sirolimus) | Experimental | Drug: SirolimusParticipants receive sirolimus daily for 1 year and are followed with serial pulmonary function tests, 6-minute walk tests, and symptom and QOL questionnaires over a 2-year period. |
| Placebo Arm | Placebo comparator | Drug: PlaceboParticipants receive placebo daily for 1 year and followed with serial pulmonary function tests, 6-minute walk tests, and symptom and QOL questionnaires over a 2-year period. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 or older
- Signed and dated informed consent
- Diagnosis of LAM based on compatible chest CT scan and a) biopsy or cytology consistent with LAM, or b) presence of tuberous sclerosis, angiomyolipoma or chylous pleural effusion; or c) a VEGF-D level of at least 800 pg/ml
- Forced expiratory volume in one second (FEV1) of 70% or less of predicted value after administration of a bronchodilator
Key exclusion criteria (18 listed)
- Known allergy to sirolimus
- History of heart attack, angina, or stroke due to clogging, narrowing, and hardening of the arteries and blood vessels
- Significant hematologic or hepatic abnormality (transaminase levels greater than three times the upper limit of normal, HCT less than 30%, platelets less than 80,000/cubic mm, adjusted absolute neutrophil count less than 1,000/cubic mm, total white blood cell count less than 3,000/cubic mm)
- Intercurrent infection at the time treatment with sirolimus begins
- Any surgery involving entry into a body cavity or requiring three or more sutures within 8 weeks of initiation of study drug
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SirolimusAlso: RapamycinA sirolimus dose of 2 tablets (1 mg/tablet) per day for 1 year. | Drug | Active Agent (Sirolimus) |
| PlaceboAlso: Other names: placeboA placebo dose of 2 tablets per day for 1 year. | Drug | Placebo Arm |
Primary outcome
Changes in Forced Expiratory Volume in One-second (FEV1) Slope in Milliliters Per Month
Time frame: Baseline to Month 12
FEV1 values reported are in liters or milliliters. There are no definite minimum and maximum values of FEV1 as it is a physiological measure of lung function and varies from individual to individual. Normative ranges are determined in populations stratified by gender, height, age and race/ethnicity. Higher FEV1 values indicate better lung function.
6 secondary outcomes
Percent of Participants With Serious Adverse Events
Time frame: Baseline to Month 12
Changes in FVC Slope in ml/Month
Time frame: Baseline to Month 12
Rate of Change in Diffusing Capacity for Carbon Monoxide (DLCO) in ml/Min/mmHg
Time frame: Baseline to Month 12
Rate of Change in Total Lung Volume in ml Per Month
Time frame: Baseline to Month 12
Rate of Change in Six Minute Walk Distance in Meters/Month
Time frame: Baseline to Month 12
Rate of Change in Serum Vascular Endothelial Growth Factor-D (VEGF-D) Levels in pg/ml Per Month
Time frame: Baseline to Month 12
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 34461049McCarthy C, Gupta N, Johnson SR, Yu JJ, McCormack FX. Lymphangioleiomyomatosis: pathogenesis, clinical features, diagnosis, and management. Lancet Respir Med. 2021 Nov;9(11):1313-1327. doi: 10.1016/S2213-2600(21)00228-9. Epub 2021 Aug 27.
- Background: PubMed 29940164Gupta N, Lee HS, Ryu JH, Taveira-DaSilva AM, Beck GJ, Lee JC, McCarthy K, Finlay GA, Brown KK, Ruoss SJ, Avila NA, Moss J, McCormack FX; NHLBI LAM Registry Group. The NHLBI LAM Registry: Prognostic Physiologic and Radiologic Biomarkers Emerge From a 15-Year Prospective Longitudinal Analysis. Chest. 2019 Feb;155(2):288-296. doi: 10.1016/j.chest.2018.06.016. Epub 2018 Jun 22.
- Background: PubMed 16210669Ryu JH, Moss J, Beck GJ, Lee JC, Brown KK, Chapman JT, Finlay GA, Olson EJ, Ruoss SJ, Maurer JR, Raffin TA, Peavy HH, McCarthy K, Taveira-Dasilva A, McCormack FX, Avila NA, Decastro RM, Jacobs SS, Stylianou M, Fanburg BL; NHLBI LAM Registry Group. The NHLBI lymphangioleiomyomatosis registry: characteristics of 230 patients at enrollment. Am J Respir Crit Care Med. 2006 Jan 1;173(1):105-11. doi: 10.1164/rccm.200409-1298OC. Epub 2005 Oct 6.
- Background: PubMed 29140122Gupta N, Finlay GA, Kotloff RM, Strange C, Wilson KC, Young LR, Taveira-DaSilva AM, Johnson SR, Cottin V, Sahn SA, Ryu JH, Seyama K, Inoue Y, Downey GP, Han MK, Colby TV, Wikenheiser-Brokamp KA, Meyer CA, Smith K, Moss J, McCormack FX; ATS Assembly on Clinical Problems. Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2017 Nov 15;196(10):1337-1348. doi: 10.1164/rccm.201709-1965ST.
- Background: PubMed 27628078McCormack FX, Gupta N, Finlay GR, Young LR, Taveira-DaSilva AM, Glasgow CG, Steagall WK, Johnson SR, Sahn SA, Ryu JH, Strange C, Seyama K, Sullivan EJ, Kotloff RM, Downey GP, Chapman JT, Han MK, D'Armiento JM, Inoue Y, Henske EP, Bissler JJ, Colby TV, Kinder BW, Wikenheiser-Brokamp KA, Brown KK, Cordier JF, Meyer C, Cottin V, Brozek JL, Smith K, Wilson KC, Moss J; ATS/JRS Committee on Lymphangioleiomyomatosis. Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016 Sep 15;194(6):748-61. doi: 10.1164/rccm.201607-1384ST.
- Results publication: PubMed 21410393McCormack FX, Inoue Y, Moss J, Singer LG, Strange C, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, 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; National Institutes of Health Rare Lung Diseases Consortium; MILES Trial Group. Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606. doi: 10.1056/NEJMoa1100391. Epub 2011 Mar 16.
- Results publication: PubMed 26799509Argula RG, Kokosi M, Lo P, Kim HJ, Ravenel JG, Meyer C, Goldin J, Lee HS, Strange C, McCormack FX; MILES Study Investigators. A Novel Quantitative Computed Tomographic Analysis Suggests How Sirolimus Stabilizes Progressive Air Trapping in Lymphangioleiomyomatosis. Ann Am Thorac Soc. 2016 Mar;13(3):342-9. doi: 10.1513/AnnalsATS.201509-631OC.
- Results publication: PubMed 30846465Gupta N, Lee HS, Young LR, Strange C, Moss J, Singer LG, Nakata K, Barker AF, Chapman JT, Brantly ML, Stocks JM, Brown KK, Lynch JP 3rd, Goldberg HJ, Downey GP, Taveira-DaSilva AM, Krischer JP, Setchell K, Trapnell BC, Inoue Y, McCormack FX; NIH Rare Lung Disease Consortium. Analysis of the MILES cohort reveals determinants of disease progression and treatment response in lymphangioleiomyomatosis. Eur Respir J. 2019 Apr 4;53(4):1802066. doi: 10.1183/13993003.02066-2018. Print 2019 Apr.
- Results publication: PubMed 24159565Young 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 3rd, Goldberg HJ, Downey GP, Swigris JJ, Taveira-DaSilva AM, Krischer JP, Trapnell BC, McCormack FX; MILES Trial Group. 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 Aug;1(6):445-52. doi: 10.1016/S2213-2600(13)70090-0.
- Results publication: PubMed 25979023Lo P, Brown MS, Kim H, Kim H, Argula R, Strange C, Goldin JG. Cyst-based measurements for assessing lymphangioleiomyomatosis in computed tomography. Med Phys. 2015 May;42(5):2287-95. doi: 10.1118/1.4916655.
- Derived from this study: PubMed 36927115Harun N, Gupta N, McCormack FX, Macaluso M. Dynamic use of historical controls in clinical trials for rare disease research: A re-evaluation of the MILES trial. Clin Trials. 2023 Jun;20(3):223-234. doi: 10.1177/17407745231158906. Epub 2023 Mar 17.
- Derived from this study: PubMed 21180274Xu KF, Wang L, Tian XL, Gui YS, Peng M, Cai BQ, Zhu YJ. The St. George's Respiratory Questionnaire in lymphangioleiomyomatosis. Chin Med Sci J. 2010 Sep;25(3):140-5. doi: 10.1016/s1001-9294(10)60038-7.
- Click here for the Health Informatics Institute of the University of South FloridaLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Francis X McCormack, MD principal investigator
University of Cincinnati Medical Center Division of Pulmonary and Critical Care Medicine
13 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Sirolimus in people with Lymphangioleiomyomatosis, run by University of Cincinnati at 13 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Japan, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Forced Expiratory Volume in One-second (FEV1) Slope in Milliliters Per Month (time frame: Baseline to Month 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00414648, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Nov 2023.