Clinical trial NCT02237625: Natural History Study of Patients With Hypophosphatasia (HPP)
Official title: Natural History Study of Adult and Pediatric Patients With Hypophosphatasia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hypophosphatasia
Keywords: Hypophosphatasia
HPP
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2014-09-11
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: FAMILY_BASED
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Up to 100 minor and 100 adult subjects will be enrolled into this natural history study.

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Medical History of HPP Patients
timeFrame: 100 years
Secondary outcomes:
measure: long-term efficacy of treatment modalities
timeFrame: 100 years
measure: potential long term complications of the disease and/or treatment
timeFrame: 100 years
measure: quality of life issues for patients living with hypophosphatasia
timeFrame: 100 years
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Priya Kishnani, MD
role: PRINCIPAL_INVESTIGATOR
References: