Clinical and Basic Investigations Into Hermansky-Pudlak Syndrome

• ClinicalTrials.gov Identifier: NCT00001456
• Recruitment Status: Recruiting
• First Posted: November 4, 1999
• Last Update Posted: April 13, 2021
• 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: April 13, 2021
• Actual Study Start Date: November 6, 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 10 different genes known to cause HPS, but only HPS-2 and HPS-10 have a basic defect whose mechanism is known, i.e., defective subunits of a coat protein, adaptor complex-3, responsible for intracellular vesicle formation. HPS-1 is a severe genetic type common in northwest Puerto Rico, and HPS-3 is a milder one seen in central Puerto Rico. HPS-4 resembles HPS-1 in severity; HPS-5 and HPS-6 resemble HPS-3 in severity. HPS-7, HPS-8, and HPS-9 are extremely rare and have not been fully characterized. The purpose of this protocol is to evaluate individuals with HPS, perform mutation analysis for known HPS-causing genes, search for variants in other genes responsible for HPS, and obtain specimens to analyze basic mechanisms of HPS.
• 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
• HPS Symptom Questionnaire
  Includes both patients and family members or caregivers.

Publications *

• 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:

Subjects with HPS age 1-80 years are eligible to enroll in this protocol.

The diagnosis of HPS is based upon a paucity or deficiency of platelet dense bodies on whole mount electron microscopy or the identification of pathogenic variants in HPS genes by genetic testing. Some subjects who have not been diagnosed with HPS may be admitted to the protocol based upon the presence of albinism and a platelet storage pool deficiency.

Most female subjects who participate in the Obstetrics/Gynecology Questionnaire will be enrolled in the protocol.

Subjects with HPS or family members who are their caregivers participating in the HPS Symptom Questionnaire will be at least 18 years of age. These subjects will enroll in the protocol and will provide written consent.

EXCLUSION CRITERIA:

Infants under age one year are excluded because there is generally no urgency for a very early diagnosis and care is more readily provided to older infants at the Clinical Center.

Pregnant women and adults who are unable to provide consent are excluded.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Year to 80 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

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: January 28, 2021