Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00467831
• Date of registration: 28/04/2007
• Prospective Registration: No
• Primary sponsor: National Human Genome Research Institute (NHGRI)
• Public title: Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
• Scientific title: Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
• Date of first enrolment: April 2007
• Target sample size: 3
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00467831
• Study type: Interventional
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: Thomas Markello, M.D.
• Affiliation: National Human Genome Research Institute (NHGRI)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

To be eligible for this protocol, participants must:

- Have a molecular diagnosis of HPS-1 or HPS-4

- Be 18-70 years of age

- Have the expectation to live more than 3 months, i.e., an FVC greater than or equal to
30% of predicted

- Have evidence of severe pulmonary fibrosis, i.e.:

1. A FVC less than or equal to 45% of predicted

2. Reduced exercise tolerance lasting longer than 1 week on the Dyspnea Perception
Scale

3. No evidence of improvement in pulmonary fibrosis within the past year, as defined
by an FVC increase of 10% or a DLco increase of 15%.

- Be available, willing, and able to come to the NIH Clinical Center for admission every
3 months.

EXCLUSION CRITERIA:

- An explanation for interstitial lung disease other than HPS, including but not limited
to radiation, sarcoidosis, hypersensitivity pneumonitis, bronchiolitis obliterans
organizing pneumonia, cancer

- Pregnancy or lactation

- History of ethanol abuse or recreational drug use in the past two years

- History of human immunodeficiency virus (HIV) or chronic viral hepatitis infection

- Chronic use of high-dose steroids (greater than 10 mg prednisone/day) intended for
ongoing treatment of their interstitial lung disease

- Use of any of the following within 28 days of enrollment: investigational therapy,
cytotoxic/immunosuppressive agents other than corticosteroids, including but not
limited to azathioprine, cyclosphosphamide, methotrexate, cyclosporine, colchicine,
interferon gamma-1b, bosentan;

- Any severe medical complication including but not be limited to uncontrolled seizures,
repeated transient ischemic attacks, severe ataxia, uncontrolled migraine headaches,
diplopia, repeated episodes of syncope, an untreated psychiatric disorder, recent
myocardial infarction (past 6 months), unstable angina, clinically relevant and
untreated arrhythmias, uncontrolled hypotension or hypertension (systolic blood
pressure less than 80 or greater than 180 mm Hg), myocarditis, severe congestive left
sided heart failure, hepatomegaly not due to right heart failure, renal glomerular
impairment (creatinine clearance less than 35 ml/min/1.73 m(2)), pancreatitis, toxic
thyroiditis, life-threatening malignancy;NOTE: right sided heart failure due to
pulmonary hypertension as a result of pulmonary fibrosis will not be considered an
exclusion criteria.

- Significant laboratory abnormalities, including but not limited to serum potassium
less than 3.0 or greater than 5.4 mEq/L, SGPT greater than 100 U/L, CK greater than
700 U/L, hemoglobin less than 9.0 g/dL, platelets less than 70 k/mm(3), leukocyte
count less than 2.0 k/microL;

- For women of child-bearing age, failure to have an effective method of birth control.
Oral contraceptives will be considered inadequate without a second method due to risk
of reduced efficacy of BCP while taking Zileuton.

- Severe psychiatric disease untreated. Inability to give informed consent after reading
or having the consent read to the participant in their native language. Any concern
that there is a therapeutic misconception will be evaluated by genetic counselor
and/or appropriate mental health professionals prior to acceptance into the study



Age minimum: 18 Years
Age maximum: 70 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hermansky-Pudlak Syndrome (HPS)

Metabolic Disease

Platelet Storage Pool Deficiency

Pulmonary Fibrosis

Oculocutaneous Albinism

Intervention(s)

Drug: Pravastatin

Drug: Erythromycin

Drug: Zileuton

Drug: Losartan

Drug: N-Acetylcysteine

Primary Outcome(s)

Survival at 2 Years [Time Frame: 24 months]

Secondary ID(s)

070132

07-HG-0132

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 02/08/2013
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00467831