HypophosphatasiaCOHIRNCT06161142
Characteristics of Hypophosphatasia in Adult Patients in Rheumatology
An observational study of Hypophosphatasia, run by University of Bonn at 1 site in Germany.
Trial summary
With hypophosphatasia still being frequently overlooked and misdiagnosed, the primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology, and beyond that to establish an algorithm that promotes early hypophosphatasia detection in clinical… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hypophosphatasia
- What is being tested?
- Second alkaline phosphatase measurement, Extended laboratory diagnostics and Symptom and clinical findings checklist for hypophosphatasia
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- 28 Feb 2023to 1 Dec 2024
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Any adult patient presenting at the University Hospital Bonn's rheumatology department with musculoskeletal complaints within the timeframe of the study conduct.
Who may be able to join
- Written Informed consent
- Age > 18 years
- Clinical suspicion of hypophosphatasia
- Evidence of a pathological ALP value within the clinical routine screening
Who cannot join
- Failure to meet the inclusion criteria listed above
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Clinic of Internal Medicine III, Department of Oncology, Haematology, Rheumatology and Clinical Immunology, University Hospital Bonn
Bonn, North Rhine-Westphalia, 53127
Valentin S. Schäfer, Dr. med., +49 228 287-17000, rheumatologie@ukbonn.de
About this study
Official title: The COHIR Study - a Non-interventional, Prospective, Single-center Investigation With Exploratory Data Analysis to Assess the Proportion of Patients With Hypophosphatasia Presenting at the Department of Rheumatology and Establishment of an Algorithm to HPP Diagnosis.
With hypophosphatasia still being frequently overlooked and misdiagnosed, the primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology, and beyond that to establish an algorithm that promotes early hypophosphatasia detection in clinical practice.
Read the detailed description
Hypophosphatasia (HPP) is a rare genetic disorder (1-3/300,000 severe cases in Europe) caused by one or more mutations in the alkaline phosphatase (ALP) gene. Hypomineralization results in symptoms such as arthralgias, insufficiency fractures, and poor dental status beginning in childhood. A fatal outcome is conceivable in circumstances of early infancy first presentation. In consistency with the musculoskeletal complaint pattern, HPP is far more common in the rheumatology patient population than in the general population.
However, HPP is still frequently misdiagnosed as some other form of bone disease (e.g., rickets, osteomalacia, or osteoporosis). Therefore, implementation of a clinically applicable algorithm for early hypophosphatasia detection is needed.
The primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology. Moreover, a further goal is to establish an algorithm that reliably separates adult HPP patients from other, rheumatologic and bone diseases.
- Conditions
- Hypophosphatasia
- Being tested
- Second alkaline phosphatase measurement, Extended laboratory diagnostics, Symptom and clinical findings checklist for hypophosphatasia, SF-36, Short physical performance battery (SPPB) score
- Keywords
- Hypophosphatasia, Hypophosphatasemia, Musculoskeletal complaints, Rare disease, Genetic disorder, Alkaline phosphatase gene, ALP, ALP gene, Rheumatic disease, COHIR study, Prevalence, Diagnostic Algorithm, Metabolic bone diseases
- Medical subject headings
- Hypophosphatasia, Rare Diseases, Genetic Diseases, Inborn, Rheumatic Diseases, Bone Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Second alkaline phosphatase measurementDiagnostic test
(2-4 weeks after the 1st measurement)
Extended laboratory diagnosticsDiagnostic test
Laboratory testing investigating features that support the diagnosis of hypophosphatasia or exclude it by indicating secondary hypophosphatasemia for other reasons (including parameters such as serum calcium, inorganic serum phosphate, vitamin B6, vitamin B12, folic acid, bone-specific alkaline phosphatase, vitamin D3, and more).
Symptom and clinical findings checklist for hypophosphatasiaDiagnostic test
Checklist including numerous symptoms and clinical findings regarding the musculoskeletal system and non-musculoskeletal body parts
SF-36Diagnostic test
Quality of life questionnaire
Short physical performance battery (SPPB) scoreDiagnostic test
The short physical performance battery is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older or disease-affected people. The scores range from 0 (worst performance) to 12 (best performance). The SPPB has been shown to have predictive validity showing a gradient of risk for mortality, nursing home admission, and disability.
Physical examinationDiagnostic test
A full rheumatological examination will be performed.
Recording of vital signsDiagnostic test
(including body temperature, blood pressure, heart rate)
Bioelectrical Impedance AnalysisDiagnostic test
A body composition measurement by BIA (Bioelectrical Impedance Analysis [proportional mass of muscle, water and fat in kg]) will be performed.
Genetic testing of the alkaline phosphatase geneDiagnostic test
Investigation of mutations regarding the alkaline phosphatase gene
| Study group | Role | What they receive |
|---|---|---|
| Persistant hypophosphatasemia | Patients with persistant hypophosphatasemia are highly suspicious for hypophosphatasia, and as such are the main focus of this study.
In case of persistently low alkaline phosphatase (2nd measurement, 2-4 weeks after the 1st measurement) with normal serum calcium and phosphate values (exclusion of secondary hypophosphatemia due to e.g. rickets or malnutrition) and exclusion of other causes of secondary hypophosphatemia, genetic testing for a pathological ALP gene is performed as part of routine diagnostics.
This study involves the structured recording of specific symptoms, the entire course of the disease since childhood, laboratory parameters and genetic testing. Receives: Diagnostic Test: Second alkaline phosphatase measurement; Diagnostic Test: Extended laboratory diagnostics; Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia; Diagnostic Test: SF-36; Diagnostic Test: Short physical performance battery (SPPB) score; Diagnostic Test: Physical examination; Diagnostic Test: Recording of vital signs; Diagnostic Test: Bioelectrical Impedance Analysis; Diagnostic Test: Genetic testing of the alkaline phosphatase gene | |
| Transient hypophosphatasemia (Control group without hypophosphatasia) | In patients, in which the initial hypophosphatasemia does not confirm with the second ALP testing, the former suspicion of hypophosphatasia must be discarded. With the exclusion of a hypophosphatasia (characterized by a persistant hypophosphatasemia among other criteria) this group of patients qualifies as a control group of patients without hypophosphatasia.
Data from this control group will be analyzed in order to investigate patient historical, clinical and laboratory features that may help in the discrimination of hypophosphatasia patients against healthy individuals. Receives: Diagnostic Test: Second alkaline phosphatase measurement; Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia; Diagnostic Test: SF-36; Diagnostic Test: Short physical performance battery (SPPB) score; Diagnostic Test: Physical examination; Diagnostic Test: Recording of vital signs; Diagnostic Test: Bioelectrical Impedance Analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Prevalence of hypophosphatasia in adult patients in rheumatology
The primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients presenting with musculoskeletal symptoms in rheumatology.
Measured: 24 months
Secondary outcomes (6)
Frequency of musculoskeletal pathology in hypophosphatasia patients in comparison with normal controls.
Frequency of musculoskeletal pathology in people with biochemistry suggestive of hypophosphatasia and positive ALP gene test as compared with normal controls.
Measured: 24 months
Health-related quality of life: Short Form-36
The possible score ranges from 0 to 100 points, where 0 points represent the greatest possible health limitation, while 100 points represent no health limitation at all.
Measured: 24 months
Frequency of specific symptoms and clinical findings in patients with hypophosphatasia
This will be derived from the symptom and clinical findings checklist.
Measured: 24 months
Frequency of specific patient history findings and the occurence of hypophosphatasia
Data will be derived from the medical history of hypophosphatasia patients (patient clinical data will be collected regarding the diagnosis, onset, progression, treatment course and outcome for patients with hypophosphatasia)
Measured: 24 months
Correlation between physical performance abnormalities and hypophosphatasia
Physical performance is determined by standardized "short physical performance battery"
Measured: 24 months
Correlation between body composition abnormalities and hypophosphatasia
Body composition is determined by bioelectrical impedance analysis.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2023
- Study start28 Feb 2023
- Primary completion1 Dec 2024 (estimated)
- Study completion1 Dec 2024 (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.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Bonn
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Valentin Schäfer, University Hospital, Bonn
- Investigators
- Valentin S. Schäfer, Dr. med., Principal investigator, University Hospital of Bonn
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06161142
- Sponsor's protocol ID
- 407/21
- Acronym
- COHIR
- Status last verified
- Dec 2023
- First submitted
- 3 Jul 2023
- Last updated
- 7 Dec 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available upon reasonable request
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The COHIR Study - a Non-interventional, Prospective, Single-center Investigation With Exploratory Data Analysis to Assess the Proportion of Patients With Hypophosphatasia Presenting at the Department of Rheumatology and Establishment of an Algorithm to HPP Diagnosis.
- ClinicalTrials.gov ID
- NCT06161142
- Acronym / sponsor ID
- COHIR / 407/21
- Conditions
- Hypophosphatasia
- Keywords
- Hypophosphatasia, Hypophosphatasemia, Musculoskeletal complaints, Rare disease, Genetic disorder, Alkaline phosphatase gene, ALP, ALP gene
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of BonnUniversity, hospital or other
- Study start
- 28 Feb 2023 (actual)
- Primary completion
- 1 Dec 2024 (estimated)
- Study completion
- 1 Dec 2024 (estimated)
- First posted
- 7 Dec 2023 (actual)
- 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.
With hypophosphatasia still being frequently overlooked and misdiagnosed, the primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology, and beyond that to establish an algorithm that promotes early hypophosphatasia detection in clinical practice.
Detailed description
Hypophosphatasia (HPP) is a rare genetic disorder (1-3/300,000 severe cases in Europe) caused by one or more mutations in the alkaline phosphatase (ALP) gene. Hypomineralization results in symptoms such as arthralgias, insufficiency fractures, and poor dental status beginning in childhood. A fatal outcome is conceivable in circumstances of early infancy first presentation. In consistency with the musculoskeletal complaint pattern, HPP is far more common in the rheumatology patient population than in the general population.
However, HPP is still frequently misdiagnosed as some other form of bone disease (e.g., rickets, osteomalacia, or osteoporosis). Therefore, implementation of a clinically applicable algorithm for early hypophosphatasia detection is needed.
The primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients in rheumatology. Moreover, a further goal is to establish an algorithm that reliably separates adult HPP patients from other, rheumatologic and bone diseases.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Persistant hypophosphatasemia | – | Diagnostic Test: Second alkaline phosphatase measurement, Diagnostic Test: Extended laboratory diagnostics, Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia, Diagnostic Test: SF-36, Diagnostic Test: Short physical performance battery (SPPB) score, Diagnostic Test: Physical examination, Diagnostic Test: Recording of vital signs, Diagnostic Test: Bioelectrical Impedance Analysis, Diagnostic Test: Genetic testing of the alkaline phosphatase genePatients with persistant hypophosphatasemia are highly suspicious for hypophosphatasia, and as such are the main focus of this study. In case of persistently low alkaline phosphatase (2nd measurement, 2-4 weeks after the 1st measurement) with normal serum calcium and phosphate values (exclusion of secondary hypophosphatemia due to e.g. rickets or malnutrition) and exclusion of other causes of secondary hypophosphatemia, genetic testing for a pathological ALP gene is performed as part of routine diagnostics. This study involves the structured recording of specific symptoms, the entire course of the disease since childhood, laboratory parameters and genetic testing. |
| Transient hypophosphatasemia (Control group without hypophosphatasia) | – | Diagnostic Test: Second alkaline phosphatase measurement, Diagnostic Test: Symptom and clinical findings checklist for hypophosphatasia, Diagnostic Test: SF-36, Diagnostic Test: Short physical performance battery (SPPB) score, Diagnostic Test: Physical examination, Diagnostic Test: Recording of vital signs, Diagnostic Test: Bioelectrical Impedance AnalysisIn patients, in which the initial hypophosphatasemia does not confirm with the second ALP testing, the former suspicion of hypophosphatasia must be discarded. With the exclusion of a hypophosphatasia (characterized by a persistant hypophosphatasemia among other criteria) this group of patients qualifies as a control group of patients without hypophosphatasia. Data from this control group will be analyzed in order to investigate patient historical, clinical and laboratory features that may help in the discrimination of hypophosphatasia patients against healthy individuals. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Any adult patient presenting at the University Hospital Bonn's rheumatology department with musculoskeletal complaints within the timeframe of the study conduct.
Key inclusion criteria (4 listed)
- Written Informed consent
- Age > 18 years
- Clinical suspicion of hypophosphatasia
- Evidence of a pathological ALP value within the clinical routine screening
Key exclusion criteria (1 listed)
- Failure to meet the inclusion criteria listed above
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 |
|---|---|---|
| Second alkaline phosphatase measurement(2-4 weeks after the 1st measurement) | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| Extended laboratory diagnosticsLaboratory testing investigating features that support the diagnosis of hypophosphatasia or exclude it by indicating secondary hypophosphatasemia for other reasons (including parameters such as serum calcium, inorganic serum phosphate, vitamin B6, vitamin B12, folic acid, bone-specific alkaline phosphatase, vitamin D3, and more). | Diagnostic test | Persistant hypophosphatasemia |
| Symptom and clinical findings checklist for hypophosphatasiaChecklist including numerous symptoms and clinical findings regarding the musculoskeletal system and non-musculoskeletal body parts | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| SF-36Quality of life questionnaire | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| Short physical performance battery (SPPB) scoreThe short physical performance battery is a group of measures that combines the results of the gait speed, chair stand and balance tests. It has been used as a predictive tool for possible disability and can aid in the monitoring of function in older or disease-affected people. The scores range from 0 (worst performance) to 12 (best performance). The SPPB has been shown to have predictive validity showing a gradient of risk for mortality, nursing home admission, and disability. | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| Physical examinationA full rheumatological examination will be performed. | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| Recording of vital signs(including body temperature, blood pressure, heart rate) | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| Bioelectrical Impedance AnalysisA body composition measurement by BIA (Bioelectrical Impedance Analysis [proportional mass of muscle, water and fat in kg]) will be performed. | Diagnostic test | Persistant hypophosphatasemia, Transient hypophosphatasemia (Control group without hypophosphatasia) |
| Genetic testing of the alkaline phosphatase geneInvestigation of mutations regarding the alkaline phosphatase gene | Diagnostic test | Persistant hypophosphatasemia |
Primary outcome
Prevalence of hypophosphatasia in adult patients in rheumatology
Time frame: 24 months
The primary aim of this prospective observational study is to determine the prevalence of hypophosphatasia in adult patients presenting with musculoskeletal symptoms in rheumatology.
6 secondary outcomes
Frequency of musculoskeletal pathology in hypophosphatasia patients in comparison with normal controls.
Time frame: 24 months
Health-related quality of life: Short Form-36
Time frame: 24 months
Frequency of specific symptoms and clinical findings in patients with hypophosphatasia
Time frame: 24 months
Frequency of specific patient history findings and the occurence of hypophosphatasia
Time frame: 24 months
Correlation between physical performance abnormalities and hypophosphatasia
Time frame: 24 months
Correlation between body composition abnormalities and hypophosphatasia
Time frame: 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2023.
- Individual participant dataSharing planned: Yes. Data will be available upon reasonable request
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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. This study is not recruiting at the moment.
Valentin S. Schäfer, Dr. med. principal investigator
University Hospital of Bonn
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 University of Bonn at 1 site in Germany.
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 4 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: status not confirmed, as of the sponsor's last update on 7 Dec 2023. 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 Germany. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Valentin S. Schäfer, Dr. med. (+49 228 287-17000, rheumatologie@ukbonn.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Prevalence of hypophosphatasia in adult patients in rheumatology (time frame: 24 months). 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 7 Dec 2023.