Characteristics of Hypophosphatasia in Adult Patients in Rheumatology

Hypophosphatasia Clinical Trial

— COHIR  

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.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06161142
• Other study ID #: 407/21
• Status: Recruiting
• Start date: February 28, 2023
• Est. completion date: December 1, 2024

Study information

• Verified date: December 2023
• Source: University of Bonn
• Contact: Valentin S. Schäfer, Dr. med.
• Phone: +49 228 287-17000
• Email: rheumatologie[@]ukbonn.de
• Is FDA regulated: No
• Study type: Observational

Clinical 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 practice.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 1, 2024
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Written Informed consent

• Age > 18 years

• Clinical suspicion of hypophosphatasia

• Evidence of a pathological ALP value within the clinical routine screening

Exclusion Criteria:

• Failure to meet the inclusion criteria listed above

Related Conditions & MeSH terms

• Hypophosphatasia

Intervention

Diagnostic Test:
• Second alkaline phosphatase measurement
(2-4 weeks after the 1st measurement)
• Extended laboratory diagnostics
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 hypophosphatasia
Checklist including numerous symptoms and clinical findings regarding the musculoskeletal system and non-musculoskeletal body parts
• SF-36
Quality of life questionnaire
• Short physical performance battery (SPPB) score
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 examination
A full rheumatological examination will be performed.
• Recording of vital signs
(including body temperature, blood pressure, heart rate)
• Bioelectrical Impedance Analysis
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 gene
Investigation of mutations regarding the alkaline phosphatase gene

Locations

Country	Name	City	State
Germany	Clinic of Internal Medicine III, Department of Oncology, Haematology, Rheumatology and Clinical Immunology, University Hospital Bonn	Bonn	North Rhine-Westphalia

Sponsors (1)

Lead Sponsor	Collaborator
University of Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	24 months
Secondary	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.	24 months
Secondary	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.	24 months
Secondary	Frequency of specific symptoms and clinical findings in patients with hypophosphatasia	This will be derived from the symptom and clinical findings checklist.	24 months
Secondary	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)	24 months
Secondary	Correlation between physical performance abnormalities and hypophosphatasia	Physical performance is determined by standardized "short physical performance battery"	24 months
Secondary	Correlation between body composition abnormalities and hypophosphatasia	Body composition is determined by bioelectrical impedance analysis.	24 months