Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

• ClinicalTrials.gov Identifier: NCT00001456
• Recruitment Status: Recruiting
• First Posted: November 4, 1999
• Last Update Posted: February 18, 2020
• Sponsor: National Human Genome Research Institute (NHGRI)
• Information provided by (Responsible Party): National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )

Tracking Information

• First Submitted Date: November 3, 1999
• First Posted Date: November 4, 1999
• Last Update Posted Date: February 18, 2020
• Actual Study Start Date: September 2, 1995
• Primary Completion Date: Not Provided

Current Primary Outcome Measures (submitted: January 19, 2019)

Natural History [ Time Frame: Ongoing ]

The natural history of Hermansky-Pudlak Syndrome (HPS)

• Original Primary Outcome Measures: Not Provided
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome
• Official Title: Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

Brief Summary

Hermansky-Pudlak Syndrome (HPS) is an inherited disease which results in decreased pigmentation (oculocutaneous albinism), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin).

The disease can cause poor functioning of the lungs, intestine, kidneys, or heart. The major complication of the disease is pulmonary fibrosis and typically causes death in patients ages 40 - 50 years old. The disorder is common in Puerto Rico, where many of the clinical research studies on the disease have been conducted. Neither the full extent of the disease nor the basic cause of the disease is known. There is no known treatment for HPS.

The purpose of this study is to perform research into the medical complications of HPS and begin to understand what causes these complications. Researchers will clinically evaluate patients with HPS of all ethnic backgrounds. They will obtain cells, blood components (plasma), and urine for future studies. Genetic tests (mutation analysis) to detect HPS-causing genes will also be conducted.<TAB>

• Detailed Description: Hermansky-Pudlak Syndrome (HPS) is a rare autosomal recessive disease consisting of oculocutaneous albinism, a platelet storage pool defect and, in some patients, lysosomal accumulation of ceroid lipofuscin. Other manifestations include pulmonary fibrosis (often fatal in the fourth or fifth decade), chronic granulomatous colitis and, rarely, renal involvement or cardiomyopathy. There exist 8 different genes known to cause HPS, but only HPS-2 has a basic defect that is known. HPS-2 disease results from mutations in the b3A subunit of a coat protein, adaptor complex-3, responsible for intracellular vesicle formation. One severe subtype of the disorder, HPS-1, is common in northwest Puerto Rico, and another milder subtype, HPS-3, is seen in central Puerto Rico. HPS-4 disease displays no founder population, and its severity resembles that of HPS-1. HPS-5 and HPS-6 resemble HPS-3 in severity. HPS-7 and HPS-8 are recently described and have not been fully characterized. In this protocol, we will clinically evaluate HPS patients of all ethnicities, obtain cells, plasma, and urine for future studies, perform mutation analysis for known HPS-causing genes, and search for other genes responsible for HPS. Routine admissions will last 4-5 days and occur approximately every two years.
• Study Type: Observational
• Study Design: Observational Model: Cohort; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: HPS patients of any gender and ethnicity age 1-80 years@@@@@@
• Condition: Hermansky-Pudlak Syndrome (HPS)
• Intervention: Not Provided

Study Groups/Cohorts

HPS

HPS patients of any gender and ethnicity age 1-80 years

Publications *

• Anikster Y, Huizing M, White J, Shevchenko YO, Fitzpatrick DL, Touchman JW, Compton JG, Bale SJ, Swank RT, Gahl WA, Toro JR. Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico. Nat Genet. 2001 Aug;28(4):376-80.
• Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I. Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky-Pudlak syndrome). N Engl J Med. 1998 Apr 30;338(18):1258-64.
• Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B. Effect of pirfenidone on the pulmonary fibrosis of Hermansky-Pudlak syndrome. Mol Genet Metab. 2002 Jul;76(3):234-42.
• Han CG, O'Brien KJ, Coon LM, Majerus JA, Huryn LA, Haroutunian SG, Moka N, Introne WJ, Macnamara E, Gahl WA, Malicdan MCV, Chen D, Krishnan K, Gochuico BR. Severe bleeding with subclinical oculocutaneous albinism in a patient with a novel HPS6 missense variant. Am J Med Genet A. 2018 Dec;176(12):2819-2823. doi: 10.1002/ajmg.a.40514. Epub 2018 Oct 4.
• El-Chemaly S, Cheung F, Kotliarov Y, O'Brien KJ, Gahl WA, Chen J, Perl SY, Biancotto A, Gochuico BR. The Immunome in Two Inherited Forms of Pulmonary Fibrosis. Front Immunol. 2018 Jan 31;9:76. doi: 10.3389/fimmu.2018.00076. eCollection 2018.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 13, 2020): 600
• Original Enrollment (submitted: June 23, 2005): 200
• Study Completion Date: Not Provided
• Primary Completion Date: Not Provided

Eligibility Criteria

• INCLUSION CRITERIA

HPS patients of any gender and ethnicity age 1-80 years are eligible to enroll in this protocol.

Patients will be diagnosed as having HPS based upon a paucity or deficiency of platelet dense bodies on whole mount electron microscopy.

Some patients who have not yet had this laboratory test will be admitted to the protocol based upon the presence of albinism combined with a platelet storage pool deficiency.

Patients with HPS or family members who are their caregivers participating in the HPS Symptom Questionnaire will be at least 18 years of age.

EXCLUSION CRITERIA

Patient will be excluded if they cannot travel to the NIH because of their medical condition.

Infants under age one.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Bernadette R Gochuico, M.D.; (301) 451-7979; gochuicb@mail.nih.gov

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00001456
• Other Study ID Numbers: 950193; 95-HG-0193
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: National Institutes of Health Clinical Center (CC) ( National Human Genome Research Institute (NHGRI) )
• Study Sponsor: National Human Genome Research Institute (NHGRI)
• Collaborators: Not Provided

Investigators

• Principal Investigator: Bernadette R Gochuico, M.D.; National Human Genome Research Institute (NHGRI)

• PRS Account: National Institutes of Health Clinical Center (CC)
• Verification Date: December 12, 2019