HypophosphatasiaNCT02796885
Characterisation of Adult-Onset Hypophosphatasia
An observational study of Hypophosphatasia, run by Sheffield Teaching Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
Trial summary
Hypophosphatasia (HPP) is an inherited condition which causes a defect in bone calcification, leading to weak bones. Early childhood forms are severe and easily recognised, and there is now a drug treatment which is very effective in children. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Hypophosphatasia
- How many people
- 60 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- Nov 2016to 31 Dec 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients attending metabolic bone services in Sheffield and Oxford, UK Patients with hypophosphatasia registered on the RUDY database.
Who may be able to join
- As the groups described above
- Able and willing to participate in the study and provide written informed consent
Who cannot join
- Other conditions known to affect serum ALP and PLP (Coeliac disease, B12 deficiency, untreated hypothyroidism, Wilson's disease)
- Taking nutritional supplements containing vitamin B6
- Pregnant
Trial locations and contacts
2 sites in 1 country.
United Kingdom2 sites
Nuffield Orthopaedic Research
Oxford, OX3 7HE
University of Sheffield
Sheffield, S10 2TN
About this study
Hypophosphatasia (HPP) is an inherited condition which causes a defect in bone calcification, leading to weak bones. Early childhood forms are severe and easily recognised, and there is now a drug treatment which is very effective in children.
Adult forms are milder, often missed by doctors or confused with osteoporosis. This is important because the usual osteoporosis treatments may be harmful in HPP, and increase the risk of broken bones. One of the reasons it is missed is a lack of research describing the typical features of HPP, so doctors don't recognise the signs, and don't know when or how to test for it.
The aim of this study is to establish clear criteria (from clinical history, examination and blood tests) to identify people with HPP. The results will also determine if there should be a trial of drug treatment for adults with HPP.
Read the detailed description
Hypophosphatasia (HPP) is a genetic disorder caused by mutation in the tissue-non-specific alkaline phosphatase gene (TNSALP). It causes impaired bone mineralisation, fractures, tooth loss, muscle weakness and possibly other adverse health outcomes.
The infantile-onset forms are severe, and were often fatal until the recent availability of a treatment (Asfotase Alfa, Alexion Pharma). The childhood-onset forms are less severe, and the adult-onset form is mild, and often unrecognised or misdiagnosed as osteoporosis.
The less severe forms of the disease are not well described, and because there has been no available treatment there has not been much research in adults. However, now that treatment is available there is a possibility of a clinical trial in adults.
Additionally, patients with hypophosphatasia are often not recognised, and are misdiagnosed as having osteoporosis. This is important because patients with hypophosphatasia are at risk of developing atypical femoral fractures if they are treated with usual osteoporosis medication (bisphosphonates).
A major contributor to the under-recognition of adult HPP is the lack of phenotypic description and biomarker definitions. The aim of this project is to identify the clinical and biochemical characteristics that identify HPP.
In preparation for this study reference ranges for the commonly used HPP biomarkers (ALP and PLP) have been established, and used to screen 2000 patients presenting to metabolic bone services in Sheffield and Oxford.
For this study, patients who have biochemistry suggestive of HPP (low ALP and high PLP), will undergo a detailed clinical assessment, with medical history, physical examination, bone biochemistry, targeted musculoskeletal imaging and HPP gene testing. Their results will be compared with a control group of metabolic bone clinic patients with normal ALP and PLP, and a group of patients with known gene-proven and clinically manifest HPP.
The results will establish clinical phenotype and biomarker criteria for HPP diagnosis, which could be incorporated into future pathways for patients presenting to metabolic bone clinics. This will improve the identification of HPP and prevent harm from incorrect treatment with bisphosphonates.
- Conditions
- Hypophosphatasia
- Being tested
- no intervention - observational study
- Medical subject headings
- Hypophosphatasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
no intervention - observational studyOther
| Study group | Role | What they receive |
|---|---|---|
| Possible hypophosphatasia | Patients attending metabolic bone services, not previously know to have HPP, with biochemistry suggestive of HPP Will have TNSALP gene test, clinical assessment for possible features of HPP, bone turnover marker profile. Receives: Other: no intervention - observational study | |
| Normal | Patients attending metabolic bone services, not previously know to have HPP, with normal HPP biochemistry Will have TNSALP gene test, clinical assessment for possible features of HPP, bone turnover marker profile. Receives: Other: no intervention - observational study | |
| Known hypophosphatasia | Patients attending metabolic bone services or registered with RUDY database, known to have HPP Will have TNSALP gene test, clinical assessment for possible features of HPP, bone turnover marker profile. Receives: Other: no intervention - observational study |
What is being measured
The primary outcome is the main question the study is designed to answer.
ALP and PLP
predictive value of low ALP with high PLP for TNSALP mutation (ROC curve)
Measured: baseline cross-sectional
Secondary outcomes (3)
ALP:PINP ratio
predictive value of ALP:PINP ratio for TNSALP mutation (ROC curve)PP
Measured: baseline cross-sectional
prevalence of imaging-confirmed musculoskeletal pathology in patients with HPP
History and clinical examination will be obtained to identify possible musculoskeletal pathology. Imaging (x-ray, ultrasound or MRI) will be obtained to determine the nature of the pathology. Will include arthritis, enthesopathy, tendonitis.
Prevalence of musculoskeletal pathology in people with biochemistry suggestive of HPP and positive gene test will be compared with normal controls.
Measured: baseline cross-sectional
short physical function battery score
physical function battery score in people with biochemistry suggestive of HPP and positive gene test (compared with normal controls)
Measured: baseline cross-sectional
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jun 2016 (estimated)
- Study startNov 2016
- Primary completion31 Dec 2019
- Study completion31 Dec 2019
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.
- 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Alexion Pharmaceuticals, Inc.
- Responsible party
- Sponsor
- Investigators
- Richard Eastell, Principal investigator, University of Sheffield
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02796885
- Sponsor's protocol ID
- STH18683
- Other IDs
- 16/NW/0385, 202179
- Status last verified
- Nov 2023
- First submitted
- 4 May 2016
- Last updated
- 15 Nov 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterisation of Adult-Onset Hypophosphatasia
- ClinicalTrials.gov ID
- NCT02796885
- Acronym / sponsor ID
- STH18683
- Conditions
- Hypophosphatasia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Sheffield Teaching Hospitals NHS Foundation TrustUniversity, hospital or other
- Collaborators
- National Institute for Health Research, United Kingdom, Alexion Pharmaceuticals, Inc.
- Study start
- Nov 2016 (actual)
- Primary completion
- 31 Dec 2019 (actual)
- Study completion
- 31 Dec 2019 (actual)
- First posted
- 13 Jun 2016 (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 an inherited condition which causes a defect in bone calcification, leading to weak bones. Early childhood forms are severe and easily recognised, and there is now a drug treatment which is very effective in children.
Adult forms are milder, often missed by doctors or confused with osteoporosis. This is important because the usual osteoporosis treatments may be harmful in HPP, and increase the risk of broken bones. One of the reasons it is missed is a lack of research describing the typical features of HPP, so doctors don't recognise the signs, and don't know when or how to test for it.
The aim of this study is to establish clear criteria (from clinical history, examination and blood tests) to identify people with HPP. The results will also determine if there should be a trial of drug treatment for adults with HPP.
Detailed description
Hypophosphatasia (HPP) is a genetic disorder caused by mutation in the tissue-non-specific alkaline phosphatase gene (TNSALP). It causes impaired bone mineralisation, fractures, tooth loss, muscle weakness and possibly other adverse health outcomes.
The infantile-onset forms are severe, and were often fatal until the recent availability of a treatment (Asfotase Alfa, Alexion Pharma). The childhood-onset forms are less severe, and the adult-onset form is mild, and often unrecognised or misdiagnosed as osteoporosis.
The less severe forms of the disease are not well described, and because there has been no available treatment there has not been much research in adults. However, now that treatment is available there is a possibility of a clinical trial in adults.
Additionally, patients with hypophosphatasia are often not recognised, and are misdiagnosed as having osteoporosis. This is important because patients with hypophosphatasia are at risk of developing atypical femoral fractures if they are treated with usual osteoporosis medication (bisphosphonates).
A major contributor to the under-recognition of adult HPP is the lack of phenotypic description and biomarker definitions. The aim of this project is to identify the clinical and biochemical characteristics that identify HPP.
In preparation for this study reference ranges for the commonly used HPP biomarkers (ALP and PLP) have been established, and used to screen 2000 patients presenting to metabolic bone services in Sheffield and Oxford.
For this study, patients who have biochemistry suggestive of HPP (low ALP and high PLP), will undergo a detailed clinical assessment, with medical history, physical examination, bone biochemistry, targeted musculoskeletal imaging and HPP gene testing. Their results will be compared with a control group of metabolic bone clinic patients with normal ALP and PLP, and a group of patients with known gene-proven and clinically manifest HPP.
The results will establish clinical phenotype and biomarker criteria for HPP diagnosis, which could be incorporated into future pathways for patients presenting to metabolic bone clinics. This will improve the identification of HPP and prevent harm from incorrect treatment with bisphosphonates.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Possible hypophosphatasia | – | Other: no intervention - observational studyPatients attending metabolic bone services, not previously know to have HPP, with biochemistry suggestive of HPP Will have TNSALP gene test, clinical assessment for possible features of HPP, bone turnover marker profile. |
| Normal | – | Other: no intervention - observational studyPatients attending metabolic bone services, not previously know to have HPP, with normal HPP biochemistry Will have TNSALP gene test, clinical assessment for possible features of HPP, bone turnover marker profile. |
| Known hypophosphatasia | – | Other: no intervention - observational studyPatients attending metabolic bone services or registered with RUDY database, known to have HPP Will have TNSALP gene test, clinical assessment for possible features of HPP, bone turnover marker profile. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients attending metabolic bone services in Sheffield and Oxford, UK Patients with hypophosphatasia registered on the RUDY database.
Key inclusion criteria (2 listed)
- As the groups described above
- Able and willing to participate in the study and provide written informed consent
Key exclusion criteria (3 listed)
- Other conditions known to affect serum ALP and PLP (Coeliac disease, B12 deficiency, untreated hypothyroidism, Wilson's disease)
- Taking nutritional supplements containing vitamin B6
- Pregnant
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| no intervention - observational study | Other | Known hypophosphatasia, Normal, Possible hypophosphatasia |
Primary outcome
ALP and PLP
Time frame: baseline cross-sectional
predictive value of low ALP with high PLP for TNSALP mutation (ROC curve)
3 secondary outcomes
ALP:PINP ratio
Time frame: baseline cross-sectional
prevalence of imaging-confirmed musculoskeletal pathology in patients with HPP
Time frame: baseline cross-sectional
short physical function battery score
Time frame: baseline cross-sectional
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2023.
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Hypophosphatasia
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. This study is not recruiting at the moment.
Richard Eastell principal investigator
University of Sheffield
2 sites 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 Sheffield Teaching Hospitals NHS Foundation Trust at 2 sites in United Kingdom.
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 2 inclusion and 3 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: finished, as of the sponsor's last update on 15 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
ALP and PLP (time frame: baseline cross-sectional). 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 15 Nov 2023.