Evaluation of Bone Architecture and Bone Strength in Adults With Hypophosphatasia (HPP) (BABS)

August 31, 2021 updated by: Nicola Hepp, Hvidovre University Hospital
The study aims to evaluate the bone architecture and bone strength in adults with Hypophosphatasia (HPP).

Study Overview

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Capital Region
      • Hvidovre, Capital Region, Denmark, 2650
        • Hvidovre University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Adults, diagnosed with HPP (genetic verified) (n=15), matched 1:1 in case of gender, age (± 5 years), BMI (± 3 kg/m2), postmenopausal status (± 2 years) with healthy controls.

Description

Inclusion criteria HPP-Group:

  • Genetically verified HPP
  • Age: ≥ 18 years
  • Persistently low levels of alkaline phosphatase (ALP) ≤ 35 U/L (normal range 35-105 U/L)
  • At least one of the following symptoms: a) dental manifestations; b) musculoskeletal pain; c) history of fracture(s)
  • Submitted informed consent

Inclusion Criteria Control-Group:

  • No ALP measurements ≤ 45 U/l and ≥ 50% of all ALP measurements, registered in the electronical clinical journal ≥ 55 U/l
  • Normal parathyroid hormone (PTH) and Pyridoxal-5´-phosphate (PLP)
  • Vitamin D3 ≥ 25 nmol/L
  • Submitted informed consent

Exclusion criteria HPP-Group:

  • Pregnancy
  • Skin infection or severe skin affection in the measurement area of microindentation
  • Known allergy to Lidocain
  • Former or current medical treatment influencing bone metabolism (oral corticosteroid > 12 weeks, former or current anti-osteoporosis treatment at any time (regardless drug holiday), all kind of sex steroids (excluding oral contraception), anti-convulsants)
  • Current malignant disorders

Exclusion Criteria Control-Group:

  • Family history of a genetic metabolic bone disease (HPP, Osteogenesis imperfecta)
  • Rickets in childhood
  • Former or current Osteoporosis
  • Former or current Osteomalacia
  • Known diabetes
  • Former or current medical treatment influencing bone metabolism (oral corticosteroid > 12 weeks, former or current anti-osteoporosis treatment at any time (regardless drug holiday), all kind of sex steroids (excluding oral contraception), anti- convulsants)
  • Skin infection or severe skin affection in the measurement area of microindentation
  • Chronic liver or gallbladder disease
  • Current malignant disorders
  • Former or current thyrotoxicosis (T4 over normal range ≥ 6 months)
  • Cushing disease
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
HPP-Group
Adults with hypophosphatasia.
Microindentation is a new technology directly measuring bone strength by a minimal invasive technique.
HRpQCT scan can assess the cross-sectional geometry of the bone and is an appropriate investigation to evaluate bone quality.
Measurement of different bone markers by biochemical analysis of blood samples.
Control-Group
Healthy control subjects.
Microindentation is a new technology directly measuring bone strength by a minimal invasive technique.
HRpQCT scan can assess the cross-sectional geometry of the bone and is an appropriate investigation to evaluate bone quality.
Measurement of different bone markers by biochemical analysis of blood samples.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Differences in Bone Mineral Strength Index (BMSi) between the two groups, assessed by microindentation (OsteoProbe®).
Time Frame: 1. October 2019 - 31.July 2020

Differences in BMSi between the HPP- and Control-Group will be evaluated by microindentation (OsteoProbe®).

Microindentation is a technology directly measuring bone strength by a minimal invasive technique. By applying a standardized pressure with a probe, which at the same time measures the indentation depth in the tibia bone, a measure of bone strength is obtained and calculated as Bone Mineral Strength Index (BMSi) [1].

1. October 2019 - 31.July 2020

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between BMSi and fracture prevalence in the HPP-Group and the Control-Group.
Time Frame: 1. October 2019 - 31.July 2020
BMSi will be evaluated by microindentation (described above). In addition, information about the occurrence of fractures in the HPP- and Control-Group will be obtained by data from the Danish National Patient Register and a structured clinical interview.
1. October 2019 - 31.July 2020
Evaluation of differences in bone microarchitecture between the HPP- and Control-Group by high resolution peripheral quantitative computed tomography (HRpQCT).
Time Frame: 1. October 2019 - 31.July 2020
To asses differences in bone architecture between the two groups, the non-dominant distal radius and non-dominant distal tibia will be examined by HRpQCT, which will provide data about total, trabecular and cortical BMD, trabecular thickness, cortical thickness, trabecular number, stiffness and finite element failure load of the radius and tibia.
1. October 2019 - 31.July 2020
Evaluation of differences in bone homeostasis between the two groups by biochemical analysis of different bone markers (P1NP, CTx, BALP, Trab-5, Sclerostin, Osteocalcin and FGF23)
Time Frame: 1. October 2019 - 31.July 2020

Blood samples will be collected for biochemical analysis of different bone markers (P1NP, CTx, BALP, Trab-5, Sclerostin, Osteocalcin and FGF23).

BALP = Bone specific alkaline phosphatase CTx = Carboxy-terminal collagen crosslinks FGF-23 = Fibroblast growth factor 23 P1NP = Procollagen type 1 amino-terminal propeptide Trab-5 = Tartrate-resistant acid phosphatase-5

1. October 2019 - 31.July 2020

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2019

Primary Completion (Anticipated)

September 30, 2021

Study Completion (Anticipated)

December 30, 2021

Study Registration Dates

First Submitted

November 18, 2019

First Submitted That Met QC Criteria

November 27, 2019

First Posted (Actual)

November 29, 2019

Study Record Updates

Last Update Posted (Actual)

September 1, 2021

Last Update Submitted That Met QC Criteria

August 31, 2021

Last Verified

August 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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