Doxycycline In Lymphangioleiomyomatosis (LAM)

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.

Sex

Female

Minimum age

18 Years

Inclusion Criteria:

* 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

Exclusion Criteria:

* Inability to give informed consent.
* Mental retardation.
* 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.

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