Clinical Trial: Characterisation of Adult-Onset Hypophosphatasia

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Observational

Official Title: Characterisation of Adult-Onset Hypophosphatasia

Brief 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.

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 Summary:

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 me
Sponsor: Sheffield Teaching Hospitals NHS Foundation Trust

Current Primary Outcome: ALP and PLP [ Time Frame: baseline cross-sectional ]

predictive value of low ALP with high PLP for TNSALP mutation (ROC curve)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • ALP:PINP ratio [ Time Frame: baseline cross-sectional ]
    predictive value of ALP:PINP ratio for TNSALP mutation (ROC curve)PP
  • prevalence of imaging-confirmed musculoskeletal pathology in patients with HPP [ Time Frame: baseline cross-sectional ]

    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.

  • short physical function battery score [ Time Frame: baseline cross-sectional ]
    physical function battery score in people with biochemistry suggestive of HPP and positive gene test (compared with normal controls)


Original Secondary Outcome: Same as current

Information By: Sheffield Teaching Hospitals NHS Foundation Trust

Dates:
Date Received: May 4, 2016
Date Started: November 2016
Date Completion: December 2017
Last Updated: November 3, 2016
Last Verified: November 2016