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NCT Number: NCT02237625

Natural History Study of Patients With Hypophosphatasia (HPP)

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.

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Key information

Conditions

Hypophosphatasia Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Metabolic Diseases Metabolism, Inborn Errors Metal Metabolism, Inborn Errors Nutritional and Metabolic Diseases

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Primary outcomes

  1. Medical History of HPP Patients

    Time frame: 100 years

    Patient clinical data will be collected related to the diagnosis, onset, progression, treatment course and outcome for patients with HPP

Secondary outcomes

  1. long-term efficacy of treatment modalities

    Time frame: 100 years

  2. potential long term complications of the disease and/or treatment

    Time frame: 100 years

  3. quality of life issues for patients living with hypophosphatasia

    Time frame: 100 years

Study contacts

Contact information is provided by the study sponsor or research team.

Janet G Blount, BA

CONTACT

[email protected]

919-681-7962

Sponsors and collaborators

Lead sponsor

Duke University

Other

Registry information

Official study title

Natural History Study of Adult and Pediatric Patients With Hypophosphatasia

Acronym: NatHisHPP

Important dates

Study start
2014
Primary completion
2027
Study completion
2028
First posted
Sep 11, 2014
Registry last updated
Mar 5, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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