Doxycycline In Lymphangioleiomyomatosis (LAM)

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by University of Nottingham.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by (Responsible Party):
University of Nottingham
ClinicalTrials.gov Identifier:
NCT00989742
First received: October 2, 2009
Last updated: June 14, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention Phase
Lymphangioleiomyomatosis
Tuberous Sclerosis
Drug: Doxycycline
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised, Double Blind, Placebo Controlled Trial of Doxycycline in Lymphangioleiomyomatosis.

Resource links provided by NLM:


Further study details as provided by University of Nottingham:

Primary Outcome Measures:
  • Mean rate of change of FEV1 over 24 months on doxycycline compared with placebo. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

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 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 40
Study Start Date: July 2009
Estimated Study Completion Date: June 2013
Estimated Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Doxycycline Drug: Doxycycline
50mg od
Placebo Comparator: Placebo Drug: Placebo
50mg od

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989742

Locations
United Kingdom
Nottingham University Hospitals
Nottingham, United Kingdom, NG7 2UH
Sponsors and Collaborators
University of Nottingham
Investigators
Principal Investigator: Simon R Johnson, DM FRCP University of Nottingham
  More Information

Publications:

Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT00989742     History of Changes
Other Study ID Numbers: 07061
Study First Received: October 2, 2009
Last Updated: June 14, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by University of Nottingham:
lymphangioleiomatosis
LAM
tuberous sclerosis
doxycycline
matrix metalloproteinases
MMP

Additional relevant MeSH terms:
Sclerosis
Tuberous Sclerosis
Lymphangioleiomyomatosis
Pathologic Processes
Hamartoma
Neoplasms
Neoplasms, Multiple Primary
Neoplastic Syndromes, Hereditary
Malformations of Cortical Development
Nervous System Malformations
Nervous System Diseases
Neurocutaneous Syndromes
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Lymphangiomyoma
Lymphatic Vessel Tumors
Neoplasms by Histologic Type
Perivascular Epithelioid Cell Neoplasms
Neoplasms, Connective and Soft Tissue
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Doxycycline
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014