HypophosphatasiaNatHisHPPNCT02237625
Natural History Study of Patients With Hypophosphatasia (HPP)
An observational study of Hypophosphatasia, run by Duke University at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Hypophosphatasia
- How many people
- 200 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2014to Sep 2028
- How long will I take part?
- 100 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Up to 100 minor and 100 adult subjects will be enrolled into this natural history study.
Who may be able to join
- 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.
Who cannot join
- Any patient without confirmation of clinical diagnosis of HPP.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Duke University Medical Center
Durham, North Carolina, 27710
Priya Kishnani, MD, 919-681-1939, kishn001@mc.duke.edu
Stephanie DeArmey, PA-C, (919) 681-1946, dearm001@mc.duke.edu
About this study
Official title: 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.
Read the 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.
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, HPP
- Medical subject headings
- Hypophosphatasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 100 years
Secondary outcomes (3)
long-term efficacy of treatment modalities
Measured: 100 years
potential long term complications of the disease and/or treatment
Measured: 100 years
quality of life issues for patients living with hypophosphatasia
Measured: 100 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2014 (estimated)
- Study startSep 2014
- Primary completionSep 2027 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HypophosphatasiaStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
- Target duration
- 100 Years
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Priya Kishnani, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02237625
- Sponsor's protocol ID
- Pro00049204
- Other IDs
- Pro00049204
- Acronym
- NatHisHPP
- Status last verified
- Mar 2026
- First submitted
- 9 Sep 2014
- Last updated
- 5 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History Study of Adult and Pediatric Patients With Hypophosphatasia
- ClinicalTrials.gov ID
- NCT02237625
- Acronym / sponsor ID
- NatHisHPP / Pro00049204
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, HPP
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Sep 2027 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 11 Sep 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Target follow-up
- 100 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Up to 100 minor and 100 adult subjects will be enrolled into this natural history study.
Key inclusion criteria (7 listed)
- 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:
- Must be current patient in the Duke University System.
Key exclusion criteria (1 listed)
- Any patient without confirmation of clinical diagnosis of HPP.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
3 secondary outcomes
long-term efficacy of treatment modalities
Time frame: 100 years
potential long term complications of the disease and/or treatment
Time frame: 100 years
quality of life issues for patients living with hypophosphatasia
Time frame: 100 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Mar 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Priya Kishnani, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hypophosphatasia, run by Duke University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 5 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Janet G Blount, BA (919-681-7962, janet.blount@duke.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Medical History of HPP Patients (time frame: 100 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Mar 2026.