Characteristics of Hypophosphatasia in Adult Patients in Rheumatology

NCT06161142 | Unknown DMC

• 1 other identifier: 407/21
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hypophosphatasia

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Frequency of musculoskeletal pathology in hypophosphatasia patients in comparison with normal controls.

  24 months

• Health-related quality of life: Short Form-36

  24 months

• Frequency of specific symptoms and clinical findings in patients with hypophosphatasia

  24 months

• Frequency of specific patient history findings and the occurence of hypophosphatasia

  24 months

• Correlation between physical performance abnormalities and hypophosphatasia

  24 months

Study Arms (2)

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.

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.

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

Interventions

Second alkaline phosphatase measurement DIAGNOSTIC_TEST

(2-4 weeks after the 1st measurement)

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

Extended laboratory diagnostics DIAGNOSTIC_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).

Persistant hypophosphatasemia

Symptom and clinical findings checklist for hypophosphatasia DIAGNOSTIC_TEST

Checklist including numerous symptoms and clinical findings regarding the musculoskeletal system and non-musculoskeletal body parts

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

SF-36 DIAGNOSTIC_TEST

Quality of life questionnaire

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

Short physical performance battery (SPPB) score DIAGNOSTIC_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.

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

Physical examination DIAGNOSTIC_TEST

A full rheumatological examination will be performed.

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

Recording of vital signs DIAGNOSTIC_TEST

(including body temperature, blood pressure, heart rate)

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

Bioelectrical Impedance Analysis DIAGNOSTIC_TEST

A body composition measurement by BIA (Bioelectrical Impedance Analysis \[proportional mass of muscle, water and fat in kg\]) will be performed.

Persistant hypophosphatasemia; Transient hypophosphatasemia (Control group without hypophosphatasia)

Genetic testing of the alkaline phosphatase gene DIAGNOSTIC_TEST

Investigation of mutations regarding the alkaline phosphatase gene

Persistant hypophosphatasemia

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Any adult patient presenting at the University Hospital Bonn's rheumatology department with musculoskeletal complaints within the timeframe of the study conduct.

You may qualify if:

• Written Informed consent
• Age \> 18 years
• Clinical suspicion of hypophosphatasia
• Evidence of a pathological ALP value within the clinical routine screening

Sponsors & Collaborators

• University of Bonn: lead

Study Sites (1)

Clinic of Internal Medicine III, Department of Oncology, Haematology, Rheumatology and Clinical Immunology, University Hospital Bonn

Bonn, North Rhine-Westphalia, 53127, Germany

RECRUITING

MeSH Terms

Conditions

Hypophosphatasia; Rare Diseases; Genetic Diseases, Inborn; Rheumatic Diseases; Bone Diseases, Metabolic

Interventions

Physical Examination

Condition Hierarchy (Ancestors)

Metal Metabolism, Inborn Errors; Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Musculoskeletal Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Bone Diseases

Intervention Hierarchy (Ancestors)

Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Valentin S. Schäfer, Dr. med.

  University Hospital of Bonn

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Valentin S. Schäfer, Dr. med.

CONTACT

+49 228 287-17000; rheumatologie@ukbonn.de

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PD Dr. med. MuDr.

Study Record Dates

• First Submitted: July 3, 2023
• First Posted: December 7, 2023
• Study Start: February 28, 2023
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: December 7, 2023

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)