Natural History Study of Patients With Hypophosphatasia (HPP) (NatHisHPP)

Natural History Study of Adult and Pediatric Patients With Hypophosphatasia

Hypophosphatasia (HPP) is a rare inherited metabolic disorder characterized by defective bone and teeth mineralization caused by mutations of the ALPL gene, which encodes for the tissue-nonspecific alkaline phosphatase (TNSALP) isozyme, resulting in decreased serum and bone alkaline phosphatase levels. To date, over 250 different mutations in the gene encoding TNSALP have been associated with HPP. Clinically, the loss of TNSALP function results in progressive skeletal impact as well as progressive impact on all other major organ systems. It clinically manifests as rickets in infants and children and osteomalacia at all ages. The severe form of the disease has been estimated to have a prevalence of about 1 in every 100,000 live births.

Study Overview

• Status: Recruiting
• Conditions: Hypophosphatasia

Detailed Description

Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a wide range of clinical expressivity, with a spectrum ranging from stillbirth without mineralized bone to early loss of teeth without bone symptoms. Depending on the age at diagnosis six clinical forms are currently recognized: perinatal (lethal), perinatal benign, infantile, childhood, adult and odontohypophosphatasia. Severe forms of HPP (perinatal and infantile) are inherited as an autosomal recessive trait and in milder forms (adult and odontohypophosphatasia) autosomal recessive and autosomal dominant inheritance coexist.

Because of the rarity of HPP as well as the side spectrum of both clinical presentation and inheritance patterns of the HPP trait, a natural history study cataloging specific clinical data with HPP would prove invaluable for future research into this disease. Specifically, it is our goal to create a comprehensive multi-discipline modality for care for hypophosphatasia patients, researching clinical manifestations of the disease such as extent of bone disease, ophthalmologic manifestations, orthopedic issues, renal issues, musculoskeletal manifestations as well as other more anecdotal findings such as those seen with cochlear implant failures and/or early menopause.

• Study Type: Observational
• Enrollment (Estimated): 200

Contacts and Locations

• Study Contact: Name: Janet G Blount, BA; Phone Number: 919-681-7962; Email: janet.blount@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: Priya Kishnani, MD; Phone Number: 919-681-1939; Email: kishn001@mc.duke.edu
      • Contact: Stephanie DeArmey, PA-C; Phone Number: (919) 681-1946; Email: dearm001@mc.duke.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Up to 100 minor and 100 adult subjects will be enrolled into this natural history study.

Description

Inclusion Criteria:

• Patients or their legal representative must provide written informed consent or, if applicable, qualify for waiver of consent.

• Patients must have a pre-established clinical diagnosis of HPP, as indicated by one or more of the following:

  • Serum alkaline phosphatase (ALP) below the age-adjusted normal range
  • Plasma PLP at least twice the upper limit of normal (no vitamin B6 administered for at least 1 week prior to determination)
  • Evidence of osteopenia or osteomalacia on skeletal radiographs
  • Genetic analysis fof the ALPL gene
• Must be current patient in the Duke University System.

Exclusion Criteria:

• Any patient without confirmation of clinical diagnosis of HPP.

Study Plan

How is the study designed?

Design Details

• Observational Models: Family-Based
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Medical History of HPP Patients; Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical History of HPP Patients	Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP	100 years

Secondary Outcome Measures

Outcome Measure	Time Frame
long-term efficacy of treatment modalities	100 years
potential long term complications of the disease and/or treatment	100 years
quality of life issues for patients living with hypophosphatasia	100 years

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Priya Kishnani, MD, Duke University

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: September 9, 2014
• First Submitted That Met QC Criteria: September 10, 2014
• First Posted (Estimated): September 11, 2014

Study Record Updates

• Last Update Posted (Actual): March 20, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Hypophosphatasia; HPP
• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Hypophosphatasia
• Other Study ID Numbers: Pro00049204 (Other Identifier: DUHS IRB)