Health Burden of Hypophosphatasia

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). 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. To know whether there is a need for a trial there is a need to determine if there is a significant personal and economic burden associated with the less severe forms of HPP.

The study consists of a clinical interview and notes review of adults and children with confirmed (by biochemical and genetic testing) HPP attending metabolic bone clinics in Sheffield to establish their clinical problems and healthcare use. There are currently about 26 adults and 8 children attending clinics in Sheffield.

The information will be used to plan a data search and health economic analysis of the burden of HPP from the UK Clinical Practice Research Database in collaboration with Pharmatelligence (a healthcare data group based within the University of Cardiff).

Study Overview

• Status: Completed
• Conditions: Hypophosphatasia
• Intervention / Treatment: Other: no intervention

Detailed Description

This is an observational retrospective study to describe the clinical problems and healthcare use of adults and children with hypophosphatasia.

Interviews will be conducted with patients with childhood- and adult-onset hypophosphatasia (and the parents of the children). Hospital notes, appointment records and GP summary care records will also be reviewed.

These sources will be used to describe their clinical problems, how these problems affect their daily function, and which healthcare services they have used.

Patients will attend for a single visit to obtain informed consent and conduct the interview.

Health problems specifically assessed in detail will include:

• Fractures
• Dental problems
• Skeletal complications
• Mobility problems
• Neurosurgical complications
• Seizures
• Respiratory complications
• Depression and anxiety
• Side effects of treatment including hypercalcaemia and hyperphosphataemia Deaths will also be recorded

Health care resource assessment will include

• Primary care episodes
• Secondary and tertiary care outpatient episodes
• In-patient episodes
• Nutritional support
• Therapy support
• Dental treatment
• Over the counter medication use

A case data report form will be developed as an iterative process through the period of the interviews to ensure that all data of potential interest is captured. Because the condition is not well described it is important that the data reported is not limited to the areas where it might be already expected to find problems.

• Study Type: Observational
• Enrollment (Actual): 28

Contacts and Locations

Study Locations

• United Kingdom
  • South Yorks
    • Sheffield, South Yorks, United Kingdom, S5 7AU
      • Academic Unit of Bone Metabolism (Sheffield)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 100 years (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adults and children with hypophosphatasia

Description

Inclusion Criteria:

• Hypophosphatasia

Exclusion Criteria:

• Unable/unwilling to give informed consent

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Adults and children with hypophosphatasia; Healthcare use interview	Other: no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
description of healthcare use	Descriptive data on which health care services the patient has used in relation to HPP	one day study visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
healthcare use appointments	descriptive data on number of healthcare encounters	one day study visit
healthcare cost	estimated healthcare cost attributable to HPP	one day study visit

Collaborators and Investigators

• Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust
• Investigators: Principal Investigator: Richard Eastell, MD FRCP, University of Sheffield

Study record dates

Study Major Dates

• Study Start: November 1, 2016
• Primary Completion (ACTUAL): December 1, 2017
• Study Completion (ACTUAL): December 1, 2017

Study Registration Dates

• First Submitted: April 1, 2016
• First Submitted That Met QC Criteria: April 21, 2016
• First Posted (ESTIMATE): April 26, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 12, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Metal Metabolism, Inborn Errors; Hypophosphatasia
• Other Study ID Numbers: STH19182