Hermansky-Pudlak Syndrome (HPS)Phase 1/2NCT00467831
Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
A Phase 1/2 study testing Losartan, Zileuton and N-Acetylcysteine in people with Hermansky-Pudlak Syndrome (HPS) and Pulmonary Fibrosis, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
This study will examine whether five drugs (pravastatin, Losartan, Zileuton, N-acetylcysteine and erythromycin) used together can slow the course of pulmonary fibrosis (scarring of the lung tissue) in patients with Hermansky-Pudlak Syndrome (HPS). Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Hermansky-Pudlak Syndrome (HPS), Pulmonary Fibrosis, Oculocutaneous Albinism
- What is being tested?
- Losartan, Zileuton and N-Acetylcysteine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2007to Nov 2012
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.:
- A FVC less than or equal to 45% of predicted
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- Reduced exercise tolerance lasting longer than 1 week on the Dyspnea Perception Scale
- 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.
Who cannot join
- 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;
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
This study will examine whether five drugs (pravastatin, Losartan, Zileuton, N-acetylcysteine and erythromycin) used together can slow the course of pulmonary fibrosis (scarring of the lung tissue) in patients with Hermansky-Pudlak Syndrome (HPS). Patients with this disease have decreased skin color (albinism), bleeding problems, and sometimes colon problems. Two of the known types of Hermansky Pudlak syndrome, type 1 and type 4, are at high risk of pulmonary fibrosis between the ages of 30 and 50.
Patients 18 to 70 years of age who have Hermansky-Pudlak Syndrome with a serious loss of lung function due to pulmonary fibrosis may be eligible for this study.
Participants begin taking pravastatin on study day 2 and start a new drug every 3 days. Patients who experience no problems with the medicines return home and continue on the drugs for the next 2 years. They return to the NIH Clinical Center every 3 months for a medical history, physical examination, and blood, urine and lung function tests. CT and bone density scans are done every year. The study may continue for up to 3 years.
Read the detailed description
Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism and a platelet storage pool defect. The most serious complication of this disorder, pulmonary fibrosis, occurs only in genetic subtypes HPS-1 and HPS-4 and is generally fatal in the fourth or fifth decade. HPS-1 is very common in northwest Puerto Rico. There is no effective treatment for the pulmonary disease of HPS (HPS-PF), which resembles idiopathic pulmonary fibrosis (IPF). A preliminary study of the antifibrotic drug, pirfenidone, gave promising results for mild to moderate HPS-PF, but not for severe pulmonary fibrosis. A second study is currently addressing only mild to moderate HPS-PF. Other drugs, studied in IPF as single agents, have some efficacy for mild to moderate disease, but none has had a major effect on mortality. Recently, a call has been made for consideration of multi-drug therapy (i.e., an oncologic approach) for severe pulmonary fibrosis. Based upon positive responses from companies producing relevant drugs, we propose a multi-drug trial using five agents: Losartan, Zileuton, a generic statin (Pravastatin), generic N-acetylcysteine, and generic Erythromycin. Participants with severe pulmonary fibrosis will be drawn largely from the Puerto Rican population. Eligibility will require a molecular diagnosis of HPS-1 or HPS-4, radiographic evidence of interstitial lung disease, persistent pulmonary function testing less than or equal to 45% of predicted after bronchodilation, and absence of other causes of lung dysfunction. Participants will be admitted to the NIH Clinical Center for a 21-day admission to establish baseline function and to begin medication therapy. Follow-up admissions (3 days) will occur every 3 months. The primary outcome parameter will be survival at 2 years.
- Conditions
- Hermansky-Pudlak Syndrome (HPS), Pulmonary Fibrosis, Oculocutaneous Albinism, Platelet Storage Pool Deficiency, Metabolic Disease
- Being tested
- Losartan, Zileuton, N-Acetylcysteine, Pravastatin, Erythromycin
- Keywords
- Restrictive Lung Disease, Pulmonary Fibrosis, Albinism, Platelet Storage Pool Deficiency, Metabolic Disease, Hermansky-Pudlak Syndrome, HPS, Lung Disease
- Medical subject headings
- Hermanski-Pudlak Syndrome, Pulmonary Fibrosis, Albinism, Oculocutaneous, Platelet Storage Pool Deficiency, Metabolic Diseases, Albinism, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LosartanDrug
Also called Cozaar
Losartan potassium tablet, 25 mg by mouth every night at bedtime.
ZileutonDrug
Also called Zyflo
Zileuton tablet, 1200 mg by mouth twice daily.
N-AcetylcysteineDrug
Also called acetylcysteine
N-acetylcysteine solution, 600 mg by mouth three times daily.
PravastatinDrug
Also called Pravachol
Pravastatin sodium tablet, 20 mg by mouth every night at bedtime.
ErythromycinDrug
Also called E-mycin, Ery-tab
Erythromycin tablet, 333 mg by mouth three times daily.
| Study group | Role | What they receive |
|---|---|---|
| Multi-Drug Regimen | Experimental | Losartan, 25 mg by mouth every night at bedtime; Zileuton, 1200 mg by mouth twice daily; N-acetylcysteine, 600 mg by mouth three times daily; Pravastatin, 20 mg by mouth every night at bedtime; Erythromycin, 333 mg by mouth three times daily. Receives: Drug: Losartan; Drug: Zileuton; Drug: N-Acetylcysteine; Drug: Pravastatin; Drug: Erythromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival at 2 Years
The number of subjects surviving after 24 months on study.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2007 (estimated)
- Study startApr 2007
- Primary completionNov 2012
- Study completionNov 2012
Why it stopped: insufficient enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Hermansky-Pudlak Syndrome (HPS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Thomas Markello, M.D., Principal investigator, National Human Genome Research Institute (NHGRI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00467831
- Sponsor's protocol ID
- 070132
- Other IDs
- 07-HG-0132
- Status last verified
- Jun 2013
- First submitted
- 28 Apr 2007
- Last updated
- 2 Aug 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Witkop CJ, Nunez Babcock M, Rao GH, Gaudier F, Summers CG, Shanahan F, Harmon KR, Townsend D, Sedano HO, King RA, et al. Albinism and Hermansky-Pudlak syndrome in Puerto Rico. Bol Asoc Med P R. 1990 Aug;82(8):333-9.
PubMed 2261023HERMANSKY F, PUDLAK P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood. 1959 Feb;14(2):162-9. No abstract available.
PubMed 13618373Huizing M, Gahl WA. Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. Curr Mol Med. 2002 Aug;2(5):451-67. doi: 10.2174/1566524023362357.
PubMed 12125811Introne WJ, Huizing M, Malicdan MCV, O'Brien KJ, Gahl WA. Hermansky-Pudlak Syndrome. 2000 Jul 24 [updated 2023 May 25]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1287/
PubMed 20301464
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of a Multi-Drug Regimen for Severe Pulmonary Fibrosis in Hermansky-Pudlak Syndrome
- ClinicalTrials.gov ID
- NCT00467831
- Acronym / sponsor ID
- 070132
- Conditions
- Hermansky-Pudlak Syndrome (HPS), Pulmonary Fibrosis, Oculocutaneous Albinism, Platelet Storage Pool Deficiency, Metabolic Disease
- Keywords
- Restrictive Lung Disease, Pulmonary Fibrosis, Albinism, Platelet Storage Pool Deficiency, Metabolic Disease, Hermansky-Pudlak Syndrome, HPS, Lung Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: insufficient enrollment
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- Apr 2007
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 1 May 2007 (estimated)
- Results
- Posted 2 Aug 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will examine whether five drugs (pravastatin, Losartan, Zileuton, N-acetylcysteine and erythromycin) used together can slow the course of pulmonary fibrosis (scarring of the lung tissue) in patients with Hermansky-Pudlak Syndrome (HPS). Patients with this disease have decreased skin color (albinism), bleeding problems, and sometimes colon problems. Two of the known types of Hermansky Pudlak syndrome, type 1 and type 4, are at high risk of pulmonary fibrosis between the ages of 30 and 50.
Patients 18 to 70 years of age who have Hermansky-Pudlak Syndrome with a serious loss of lung function due to pulmonary fibrosis may be eligible for this study.
Participants begin taking pravastatin on study day 2 and start a new drug every 3 days. Patients who experience no problems with the medicines return home and continue on the drugs for the next 2 years. They return to the NIH Clinical Center every 3 months for a medical history, physical examination, and blood, urine and lung function tests. CT and bone density scans are done every year. The study may continue for up to 3 years.
Detailed description
Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism and a platelet storage pool defect. The most serious complication of this disorder, pulmonary fibrosis, occurs only in genetic subtypes HPS-1 and HPS-4 and is generally fatal in the fourth or fifth decade. HPS-1 is very common in northwest Puerto Rico. There is no effective treatment for the pulmonary disease of HPS (HPS-PF), which resembles idiopathic pulmonary fibrosis (IPF). A preliminary study of the antifibrotic drug, pirfenidone, gave promising results for mild to moderate HPS-PF, but not for severe pulmonary fibrosis. A second study is currently addressing only mild to moderate HPS-PF. Other drugs, studied in IPF as single agents, have some efficacy for mild to moderate disease, but none has had a major effect on mortality. Recently, a call has been made for consideration of multi-drug therapy (i.e., an oncologic approach) for severe pulmonary fibrosis. Based upon positive responses from companies producing relevant drugs, we propose a multi-drug trial using five agents: Losartan, Zileuton, a generic statin (Pravastatin), generic N-acetylcysteine, and generic Erythromycin. Participants with severe pulmonary fibrosis will be drawn largely from the Puerto Rican population. Eligibility will require a molecular diagnosis of HPS-1 or HPS-4, radiographic evidence of interstitial lung disease, persistent pulmonary function testing less than or equal to 45% of predicted after bronchodilation, and absence of other causes of lung dysfunction. Participants will be admitted to the NIH Clinical Center for a 21-day admission to establish baseline function and to begin medication therapy. Follow-up admissions (3 days) will occur every 3 months. The primary outcome parameter will be survival at 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multi-Drug Regimen | Experimental | Drug: Losartan, Drug: Zileuton, Drug: N-Acetylcysteine, Drug: Pravastatin, Drug: ErythromycinLosartan, 25 mg by mouth every night at bedtime; Zileuton, 1200 mg by mouth twice daily; N-acetylcysteine, 600 mg by mouth three times daily; Pravastatin, 20 mg by mouth every night at bedtime; Erythromycin, 333 mg by mouth three times daily. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.:
- Be available, willing, and able to come to the NIH Clinical Center for admission every 3 months.
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LosartanAlso: CozaarLosartan potassium tablet, 25 mg by mouth every night at bedtime. | Drug | Multi-Drug Regimen |
| ZileutonAlso: ZyfloZileuton tablet, 1200 mg by mouth twice daily. | Drug | Multi-Drug Regimen |
| N-AcetylcysteineAlso: acetylcysteineN-acetylcysteine solution, 600 mg by mouth three times daily. | Drug | Multi-Drug Regimen |
| PravastatinAlso: PravacholPravastatin sodium tablet, 20 mg by mouth every night at bedtime. | Drug | Multi-Drug Regimen |
| ErythromycinAlso: E-mycin, Ery-tabErythromycin tablet, 333 mg by mouth three times daily. | Drug | Multi-Drug Regimen |
Primary outcome
Survival at 2 Years
Time frame: 24 months
The number of subjects surviving after 24 months on study.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 2261023Witkop CJ, Nunez Babcock M, Rao GH, Gaudier F, Summers CG, Shanahan F, Harmon KR, Townsend D, Sedano HO, King RA, et al. Albinism and Hermansky-Pudlak syndrome in Puerto Rico. Bol Asoc Med P R. 1990 Aug;82(8):333-9.
- Background: PubMed 13618373HERMANSKY F, PUDLAK P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood. 1959 Feb;14(2):162-9. No abstract available.
- Background: PubMed 12125811Huizing M, Gahl WA. Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. Curr Mol Med. 2002 Aug;2(5):451-67. doi: 10.2174/1566524023362357.
- Background: PubMed 20301464Introne WJ, Huizing M, Malicdan MCV, O'Brien KJ, Gahl WA. Hermansky-Pudlak Syndrome. 2000 Jul 24 [updated 2023 May 25]. In: Adam MP, Bick S, Mirzaa GM, Wallace SE, Amemiya A, editors. GeneReviews(R) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. Available from http://www.ncbi.nlm.nih.gov/books/NBK1287/
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Markello, M.D. principal investigator
National Human Genome Research Institute (NHGRI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Losartan, Zileuton and N-Acetylcysteine in people with Hermansky-Pudlak Syndrome (HPS) and Pulmonary Fibrosis, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Aug 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Aug 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival at 2 Years (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00467831, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Aug 2013.