LymphangioleiomyomatosisPhase 2TRAILNCT01353209
Letrozole for Lymphangioleiomyomatosis
A Phase 2 study testing Letrozole in people with Lymphangioleiomyomatosis, run by University of Cincinnati at 9 sites in United States.
Trial summary
The hypothesis in this study is that estrogen suppression by an aromatase inhibitor in postmenopausal women with lymphangioleiomyomatosis (LAM) will prevent or delay progression of lung disease and result in a decrease in the rate of decline in FEV1 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?
- Letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 9 sitesUnited States
- Study dates
- May 2011to Sep 2014
- Phase
- Phase 2
- 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
- Definite diagnosis of based on compatible chest CT and at least one of the following:
- biopsy or cytology consistent with LAM, or
- tuberous sclerosis, renal angiomyolipoma, cystic abdominal lymphangiomas, or chylous effusion in the chest or abdomen, or
- serum VEGF-D ≥ 800 pg/uL.
- post bronchodilator FEV1 ≤80% predicted or DLCO ≤70% predicted or RV≥120% predicted
- female and postmenopausal status as defined by one of the following:
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- prior bilateral oophorectomy or bilateral ovarian irradiation, or
- age greater than 55 years, and no menstrual period for 12 months or longer.
- age 18-55 years and estradiol level in the postmenopausal range in the absence of current use of progestational agents.
- If still premenopausal, may enter if rendered medically postmenopausal on clinical grounds with the use of gonadotropin releasing hormone (e.g. leuprolide), as long as serum estradiol, FSH, and LH are in the postmenopausal range
- Patients with osteopenia or osteoporosis must be receiving appropriate treatment for their osteoporosis or osteopenia at entry into this study.
Who cannot join
- Known allergy to letrozole
- Inability to comply with pulmonary function tests or follow up visits.
- Treatment with investigational agents within 30 days
- Hormonal therapy (e.g. estrogen, progestin, LHRH agonists or antagonists, estrogen receptor blockers, estrogen receptor down regulators, aromatase inhibitors) within 30 days month of registration
- Medical or psychiatric conditions that would interfere with the ability to provide informed consent.
- abnormal hematologic and hepatic function as defined by the following at the time of randomization.:
Show all 9Show fewer
- Neutrophils < 1500/mm3 and platelets < 100,000/mm3
- Bilirubin < 1.25 X upper limit of normal
- SGPT (ALT) or SGOT (AST) >2.5 X upper limit of normal
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
University of Cincinnati
Cincinnati, Ohio, 45267
Cleveland Clinic
Cleveland, Ohio, 44195
Mayo Clinic
Jacksonville, Florida, 32224
Loyola University Medical Center
Maywood, Illinois, 60153
University of Miami
Miami, Florida, 33136
Minor and James
Seattle, Washington, 98122
Washington University School of Medicine
St Louis, Missouri, 63110
Stanford University Medical Center
Stanford, California, 94305
About this study
Official title: Trial of Letrozole in Lymphangioleiomyomatosis
The hypothesis in this study is that estrogen suppression by an aromatase inhibitor in postmenopausal women with lymphangioleiomyomatosis (LAM) will prevent or delay progression of lung disease and result in a decrease in the rate of decline in FEV1
Read the detailed description
Lymphangioleiomyomatosis, or LAM, is an uncommon, progressive, cystic lung disease that predominantly affects young women. Pulmonary parenchymal changes consistent with LAM are found in about one third of women with tuberous sclerosis complex (TSC), an autosomal dominant tumor suppressor syndrome. LAM also occurs in a sporadic form that is not associated with germline mutations in TSC genes. Recent evidence that recurrent LAM after lung transplantation results from seeding of the graft from a remote source and suggests a metastatic mechanism for the disease.
Since LAM occurs almost exclusively in women, and is exacerbated by pregnancy, menses and hormonal therapies suggest that estrogen suppression might be expected to prevent or delay progression of disease.
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues can therefore be achieved by specifically inhibiting the aromatase enzyme. Letrozole is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis) that has been shown to be effective in other neoplasms that affect women, such as breast cancer.
- Conditions
- Lymphangioleiomyomatosis
- Being tested
- Letrozole, Placebo
- Keywords
- Lymphangiomyomatosis, Postmenopausal
- Medical subject headings
- Lymphangioleiomyomatosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LetrozoleDrug
Also called Femara
2.5 mg daily for twelve months
PlaceboDrug
Also called sugar pill
placebo given daily for twelve months
| Study group | Role | What they receive |
|---|---|---|
| Letrozole | Experimental | Patients are placed on letrozole, 1 tablet (2.5 mg) daily for one year Receives: Drug: Letrozole |
| Placebo | Placebo comparator | Patients are placed on placebo, 1 tablet daily for one year Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Change in Forced Expiratory Volume in 1 Second in ml/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. Higher FEV1 scores indicate better lung function.
Measured: 12 months
Secondary outcomes (3)
Post-bronchodilator FVC
Post-bronchodilator FVC in milliliters
Measured: twelve months
St George Respiratory Questionnaire
Quality of Life scale for respiratory symptoms. This is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease. Scores range from 0 to 100, with higher scores indicating worse quality of life.
Measured: twelve months
Serum VEGF-D
VEGF-D values represent serum VEGF-D levels in pg/ml. Higher levels of VEGF-D are associated with Lymphangioleiomyomatosis. A serum VEGF-D greater than 400 pg/ml is a diagnostic biomarker for LAM.
Measured: twelve months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2011 (estimated)
- Study startMay 2011
- Primary completionSep 2014
- Study completionSep 2014
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 (1)Papers the sponsor has linked to this study.
- Other trials for LymphangioleiomyomatosisStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Cincinnati
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Defense
- Responsible party
- Principal investigator, Francis McCormack, University of Cincinnati
- Investigators
- Francis X McCormack, MD, Principal investigator, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01353209
- Sponsor's protocol ID
- 5708
- Acronym
- TRAIL
- Status last verified
- Apr 2024
- First submitted
- 11 May 2011
- Last updated
- 17 Apr 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- Yes: Deidentified demographics and outcomes can be shared. Because LAM is a rare disease, demographics will be limited. A data transfer agreement will be implemented between the University of Cincinnati and the requesting entity.
Publications
Lu C, Lee HS, Pappas GP, Dilling DF, Burger CD, Shifren A, Veeraraghavan S, Chapman JT, Parambil J, Ruoss SJ, Young LR, Hammes SR, Kopras EJ, Roads T, Krischer JP, McCormack FX; Trial of an Aromatase Inhibitor in Lymphangioleiomyomatosis Group. A Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis. Ann Am Thorac Soc. 2017 Jun;14(6):919-928. doi: 10.1513/AnnalsATS.201610-824OC.
PubMed 28570161
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Letrozole in Lymphangioleiomyomatosis
- ClinicalTrials.gov ID
- NCT01353209
- Acronym / sponsor ID
- TRAIL / 5708
- Conditions
- Lymphangioleiomyomatosis
- Keywords
- Lymphangiomyomatosis, Postmenopausal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University of CincinnatiUniversity, hospital or other
- Collaborators
- United States Department of Defense
- Study start
- May 2011
- Primary completion
- Sep 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 12 May 2011 (estimated)
- Results
- Posted 17 Apr 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis in this study is that estrogen suppression by an aromatase inhibitor in postmenopausal women with lymphangioleiomyomatosis (LAM) will prevent or delay progression of lung disease and result in a decrease in the rate of decline in FEV1
Detailed description
Lymphangioleiomyomatosis, or LAM, is an uncommon, progressive, cystic lung disease that predominantly affects young women. Pulmonary parenchymal changes consistent with LAM are found in about one third of women with tuberous sclerosis complex (TSC), an autosomal dominant tumor suppressor syndrome. LAM also occurs in a sporadic form that is not associated with germline mutations in TSC genes. Recent evidence that recurrent LAM after lung transplantation results from seeding of the graft from a remote source and suggests a metastatic mechanism for the disease.
Since LAM occurs almost exclusively in women, and is exacerbated by pregnancy, menses and hormonal therapies suggest that estrogen suppression might be expected to prevent or delay progression of disease.
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues can therefore be achieved by specifically inhibiting the aromatase enzyme. Letrozole is a nonsteroidal aromatase inhibitor (inhibitor of estrogen synthesis) that has been shown to be effective in other neoplasms that affect women, such as breast cancer.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Letrozole | Experimental | Drug: LetrozolePatients are placed on letrozole, 1 tablet (2.5 mg) daily for one year |
| Placebo | Placebo comparator | Drug: PlaceboPatients are placed on placebo, 1 tablet daily for one year |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Definite diagnosis of based on compatible chest CT and at least one of the following:
- post bronchodilator FEV1 ≤80% predicted or DLCO ≤70% predicted or RV≥120% predicted
- female and postmenopausal status as defined by one of the following:
- Patients with osteopenia or osteoporosis must be receiving appropriate treatment for their osteoporosis or osteopenia at entry into this study.
Key exclusion criteria (9 listed)
- Known allergy to letrozole
- Inability to comply with pulmonary function tests or follow up visits.
- Treatment with investigational agents within 30 days
- Hormonal therapy (e.g. estrogen, progestin, LHRH agonists or antagonists, estrogen receptor blockers, estrogen receptor down regulators, aromatase inhibitors) within 30 days month of registration
- Medical or psychiatric conditions that would interfere with the ability to provide informed consent.
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 |
|---|---|---|
| LetrozoleAlso: Femara2.5 mg daily for twelve months | Drug | Letrozole |
| PlaceboAlso: sugar pillplacebo given daily for twelve months | Drug | Placebo |
Primary outcome
Rate of Change in Forced Expiratory Volume in 1 Second in ml/Month
Time frame: 12 months
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. Higher FEV1 scores indicate better lung function.
3 secondary outcomes
Post-bronchodilator FVC
Time frame: twelve months
St George Respiratory Questionnaire
Time frame: twelve months
Serum VEGF-D
Time frame: twelve months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 28570161Lu C, Lee HS, Pappas GP, Dilling DF, Burger CD, Shifren A, Veeraraghavan S, Chapman JT, Parambil J, Ruoss SJ, Young LR, Hammes SR, Kopras EJ, Roads T, Krischer JP, McCormack FX; Trial of an Aromatase Inhibitor in Lymphangioleiomyomatosis Group. A Phase II Clinical Trial of an Aromatase Inhibitor for Postmenopausal Women with Lymphangioleiomyomatosis. Ann Am Thorac Soc. 2017 Jun;14(6):919-928. doi: 10.1513/AnnalsATS.201610-824OC.
- Individual participant dataSharing planned: Yes. Deidentified demographics and outcomes can be shared. Because LAM is a rare disease, demographics will be limited. A data transfer agreement will be implemented between the University of Cincinnati and the requesting entity.
Related trials for Lymphangioleiomyomatosis
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TSC Biosample Repository and Natural History Database
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Tuberous Sclerosis Complex and Lymphangioleiomyomatosis Pregnancy Registry (TSC-LAM Registry)
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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
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Letrozole in people with Lymphangioleiomyomatosis, run by University of Cincinnati at 9 sites in United States.
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 11 inclusion and 9 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 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 17 Apr 2024). 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?
Rate of Change in Forced Expiratory Volume in 1 Second in ml/Month (time frame: 12 months). 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 NCT01353209, which also lists 1 linked publication.
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 17 Apr 2024.