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The purpose of the study is to test if the drug doxycycline is effective in slowing the progression of lung disease in LAM. Lymphangioleiomyomatosis (LAM) is a rare lung disease which affects young women. Women with LAM develop enlarged air spaces in the lungs called cysts, caused by an excess of matrix metalloproteinases (MMPs), protein-digesting enzymes. LAM is associated with kidney tumours, called angiomyolipomas, and causes recurrent lung collapse, breathlessness and death or need for lung transplant. There is no proven treatment. Doxycycline, a commonly used antibiotic can block MMP production and a small number of patients have shown some benefit from doxycycline. The investigators will perform a study to test if doxycycline can slow the fall in lung function in patients with LAM. Forty patients who consent to participate will take doxycycline or a placebo (dummy) tablet for two years in addition to their standard treatment.
Mean rate of change of FEV1 over 24 months on doxycycline compared with placebo. [ Time Frame: 2 years ]
Secondary Outcome Measures :
Rate change FVC over 24 months Change DLCO at 12 & 24 mths Change in shuttle walk distance at 12 & 24 mths Change in QOL at 12 & 24 mths Time to composite safety endpoint Number complications Number respiratory infections Adverse effects [ Time Frame: 2 years ]
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Ages Eligible for Study:
18 Years and older (Adult, Senior)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
Sporadic LAM diagnosed either by cystic lung disease on HRCT classical of LAM plus angiomyolipoma or chylous effusion or cystic lung disease on HRCT and tissue biopsy showing LAM or angiomyolipoma
TSC-LAM diagnosed by cystic lung disease on HRCT and tuberous sclerosis diagnosed by TSC consensus criteria(13).
Patients with either an FEV1 below 80% predicted or evidence of a 20% deterioration in FEV1.
Hormone and bronchodilator treatment for LAM* is allowed providing treatment has not changed in the three months prior to enrollment.
progesterone, GnRh agonists and bronchodilators
Inability to give informed consent.
Age less than 18 years.
Pneumothorax, chylous effusion, bleeding angiomyolipoma or change in hormone treatment within 3 months.
Previous organ transplantation.
Severe or uncontrolled epilepsy.
Use of any oral contraceptive pill.
Pregnancy or breast feeding. Pre-menopausal patients must be willing to use appropriate birth control measures to avoid pregnancy while enrolled in the study.
Major systemic diseases (malignancy, myocardial infarction or unstable angina, type1 diabetes, severe hypertension, liver cirrhosis).
Use of drugs known to interact with doxycycline, including anticoagulation with warfarin.
Anticoagulation with warfarin.
Hypersensitivity to tetracyclines.
Treatment with mTOR inhibitor within the previous 3 months (sirolimus, everolimus).
Use of doxycycline or other experimental drug within the previous three months.
Sclerosis Tuberous Sclerosis
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development, Group I
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Genetic Diseases, Inborn
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Perivascular Epithelioid Cell Neoplasms
Neoplasms, Connective and Soft Tissue
Immune System Diseases