Clinical trial: Minocycline Therapy for Lung Scarring in Patients With Idiopathic Pulmonary Fibrosis - a Pilot Study (NCT00203697)

Eligibility criteria:
Inclusion Criteria:

          1. Clinical symptoms consistent with idiopathic pulmonary fibrosis (IPF) of > 3 months
             duration (insidious onset of otherwise unexplained dyspnea on exertion and bibasilar
             inspiratory crackles)

          2. Age 20 through 79, inclusive. Patients ages 20-34 must have diagnosis by either open
             or video-assisted thoracoscopic (VATS) lung biopsy to be eligible.

          3. Diagnosis must be made by high-resolution (HRCT) chest CT showing definite or probable
             IPF AND within 30 months prior to screening either of the following):

               -  Open or VATS lung biopsy showing definite or probable usual interstitial
                  pneumonia (UIP), required for subjects ages 20-34 due to the rarity of IPF in
                  this age group OR

               -  Non-diagnostic transbronchial biopsy to exclude other conditions (including
                  granulomatous disease, sarcoidosis, hypersensitivity pneumonitis) AND

               -  abnormal pulmonary function tests (reduced FVC or decreased DLCO or impaired gas
                  exchange at rest or during exercise)

             AND 2 of the following:

               1. Age > 50 years

               2. Insidious onset of otherwise unexplained dyspnea on exertion

               3. Bibasilar, inspiratory crackles (dry or Velcro type in character)

          4. Currently on low dose (< 0.3 mg/kg LBW) prednisone plus azathioprine or
             cyclophosphamide per ATS Consensus for at least 28 days prior to study treatment and
             intending to continue the same therapy until the end of study treatment. This therapy
             may be preceded by a course of higher-dose prednisone at the discretion of the
             treating physician.

          5. FVC > 40% and < 90% of predicted (Hankinson/NHANES2) value at screening.

          6. DLCO > 20% of predicted (Neas/NHANES3) value at screening.

          7. PaO2 > 50 mmHg at rest after 20 minutes on room air at baseline.

          8. Able to understand and sign a written informed consent form and comply with the
             requirements of the study.

        Exclusion criteria

        Patients with any of the following will be excluded from the study:

          1. History of clinically significant environmental exposure known to cause pulmonary
             fibrosis (drugs, asbestos, beryllium, radiation, domestic birds, etc).

          2. Known explanation for interstitial lung disease, other than IPF, including but not
             limited to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis
             obliterans organizing pneumonia (BOOP), and cancer.

          3. Diagnosis of any connective tissue disease (scleroderma, SLE, rheumatoid arthritis,
             etc.) according to the American College of Rheumatology criteria. Antinuclear antibody
             (UCLA test # 0737, $39) ≥1:160, rheumatoid factor (UCLA test #0881, $29) >25, Scl-70
             positive (UCLA test #1977, $12), anticentromere antibodies positive (UCLA test #16232,
             $15) at baseline. These lab tests are considered minimum standard of care. Additional
             criteria, if evaluated (preferred standard of care) ENA (SM & RNP) (UCLA test number
             16393, $36) positive and double strand DNA (UCLA test number 0797, $67) positive.

          4. Any condition other than IPF, which in the opinion of the investigator, is likely to
             result in the death of the patient within the next year.

          5. Evidence of active infection including bronchitis, sinusitis, UTI, cellulitis within 1
             week prior to treatment.

          6. History of unstable or deteriorating cardiac or neurologic disease, including but not
             limited to:

               1. Myocardial infarction, coronary artery bypass surgery or angioplasty within the
                  past 6 months

               2. Congestive heart failure requiring hospitalization within the past 6 months

               3. Uncontrolled arrhythmia

               4. Stroke or TIAs within 18 months

          7. Pregnant or lactating females. Females of child bearing potential are required to have
             a negative serum or urine pregnancy test prior to enrollment and agree to practice
             abstinence or prevent pregnancy by a medically acceptable method of birth control
             (e.g. barrier methods, IUD, Norplant, Provera injection or oral birth control pills).

          8. Liver function above specific limits. Total bilirubin > 1.5 X ULN, transaminases (AST,
             SGOT) or (ALT, SGPT) > 3 ULN, alkaline phosphatase > 3 ULN.

          9. Hematology outside of specified limits, WBC <2,500/mm3, hematocrit <30 or >59,
             platelets <100,000/mm3 at screening.

         10. TSH outside the normal range (with or without thyroid supplementation at a stable dose
             for 3 months).

         11. Investigational therapy for any indication within 28 days prior to treatment.

         12. Investigational or clinical therapy including tetracycline (or derivatives),
             cyclosporin, methotrexate, chlorambucil, colchicine, d-penicillamine, pirfenidone,
             interferon-beta or interferon-gamma or other drugs (other than corticosteroids and
             azathioprine or cyclophosphamide) potentially affecting IPF within 6 months prior to
             treatment

         13. Lung transplantation

         14. Patients who would not be able to comply with the requirements for the trial.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 20 Years old.
Subject must be at most 79 Years

Patient description (medical language): A 47-year-old man comes to the office for routine checkup. He is complaining of chronic cough and occasional but progressive dyspnea.  Other medical conditions include hypertension and osteoarthritis.  The patient smokes a pack of cigarettes daily and does not use alcohol or illicit drugs.  He used to be a construction worker. On examination, there are decreased breath sounds and percussive dullness at the base of both lungs.  Chest CT scan reveals a mild bilateral pleural effusion and diffuse thickening of the pleura. The patient's documents show chronic exposure to asbestosis. The specimen of the lungs reveled  pulmonary fibrosis that is most predominant in the lower lobes, characterized  by the presence of asbestos bodies (golden-brown beaded rods with translucent centers).

Patient description (patient's own words): I'm a 47-year-old former construction worker. I'm a man and I smoke a pack of cigs a day but I don't drink or do drugs. I went to my routine checkup because I've been coughing so much lately. I also had shortness of breath and it got worse over time. I already suffer from hypertension and osteoarthritis. My doctor found that I have decreased breath sounds. I did a chest scan and it seems that I have fluid around my lungs, and the lining of my lungs has become thicker in many areas. I have been exposed a lot to asbestos fibers. The other lung exam showed that I have pulmonary fibrosis, especially in the lower part of my lungs and they found some asbestos there.

Does the patient match the trial criteria? Entailment