Minocycline Therapy for Lung Scarring in Patients With Idiopathic Pulmonary Fibrosis - a Pilot Study

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00203697
• Date of registration: 13/09/2005
• Prospective Registration: Yes
• Primary sponsor: University of California, Los Angeles
• Public title: Minocycline Therapy for Lung Scarring in Patients With Idiopathic Pulmonary Fibrosis - a Pilot Study
• Scientific title: Minocycline Treatment in Patients With Idiopathic Pulmonary Fibrosis Being Treated With Standard of Care Therapy- a Pilot Study
• Date of first enrolment: April 2006
• Recruitment status: Active, not recruiting
• URL: http://clinicaltrials.gov/show/NCT00203697
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment
• Phase: Phase 3

Countries of recruitment

United States

Contacts

• Name: Eric Kleerup, MD
• Affiliation: University of California, Los Angeles

Key inclusion & exclusion 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.



Age minimum: 20 Years
Age maximum: 79 Years
Gender: Both

Health Condition(s) or Problem(s) studied

Idiopathic Pulmonary Fibrosis

Intervention(s)

Drug: minocycline

Secondary ID(s)

09-002Kleerup

NIH-NHLBI 1 P50 HL67665-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors