Genetic Analysis to Predict the Development of Paget's Disease

NCT05309954 | Active Not Recruiting

• 3 other identifiers: AC1905619/ES/0141259285
• Study Type: observational
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Paget's disease of the bone (PDB) is a skeletal disorder with a strong genetic component which can be associated with various complications such as pain, bone deformity, arthritis and deafness. Recent advances in understanding the genetic determinants of PDB offer the prospect of developing a genetic profiling test which can be offered to people with a parent or sibling with PDB to determine how likely they are to develop the disease themselves. The aim of the study is to perform genetic testing for variants associated with PDB in people aged 45 and above who have a parent or sibling (first degree relative) with the disease. The Investigators will assess how well genetic profiling performs in predicting PDB by performing an imaging technique called a radionuclide bone scan which is a very sensitive way of detecting early PDB. This scan will be performed on entry to the study and again after five years. The reason for performing two scans five years apart because PDB becomes more common with age and so this will allow the Investigators to give an accurate indication of how good the genetic profiling test is in people at different ages. In addition to genetic profiling the investigators will analyse blood samples for biochemical markers of PDB and also test saliva and stool samples for the microbiome profile since its thought that this may influence risk of the disease as well. In the longer term the investigators hope the study will allow them to develop a blood test to stratify for risk of PDB and use bone scans only in people who the clinicians think are at highest risk of developing the disease. This will allow people with PDB to be picked up early allowing treatment to be given in a timely manner.

Conditions

Paget Disease; Paget Disease of Bone

Outcome Measures

Primary Outcomes (3)

• PRIMARY ENDPOINTS - Identify Genetic Markers that are associated with the increased presence of PDB lesions in people with a family history of the disorder, as assessed by a radionuclide bone scan

  Genetic and Transcriptome profile of each participant will be produced and analysed to determine if there is any association between specific genes and a increase in the presence of PDB lesions in people with a family history of the disorder. PDB lesions will be assessed by a radionuclide bone scan

  5 years

• Primary Endpoint (Participant arm): The proportion of patients that develop PDB-like bone lesions

  The proportion of participants who have a family history of PDB that develop PDB-like bone lesions by the end of study assessed by radionuclide bone scan.

  5 years

• Primary Endpoint (Participant arm): T proportion of individuals that develop abnormalities suggestive of PDB

  The primary endpoint will be to evaluate the proportion of individuals that develop biochemical or clinical abnormalities suggestive of PDB over a the 5-year duration of the trial

  5 years

Secondary Outcomes (6)

• Secondary Endpoint - Analysis of scores in SF36 (36-Item Short Form Survey)

  5 years

• Secondary Endpoint- Analysis of scores in HAQ (Health Assessment Questionnaire)

  5 years

• Secondary Endpoint - Analysis of scores in EQ5D (EuroQol five dimension scale)

  5 years

• Secondary Endpoint - Analysis of scores in IPAQ (International Physical Activity Questionnaire)

  5 years

• Secondary Endpoint - Analysis of scores in BPI (Brief Pain Inventory Scale) scores.

  5 years

Study Arms (2)

Observational (With Bone Scan)

Individuals with a Family history of Paget's disease of bone (PDB) affecting first degree relative such as a parent or sibling that have not already diagnosed with PDB

Observational (Without Bone scan)

Individuals, that are spouses, friends and/or non blood relatives of the individuals with a family history of PDB.

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

We will aim to recruit up to individuals (Cases) with a positive family history of PDB and Spouses, friends and or unrelated relatives of the cases as a control cohort.

You may qualify if:

• Family history of PDB affecting first degree relative such as a parent or sibling.
• Not already diagnosed with PDB
• Participant willing and able to consent and comply with the study protocol.
• Age \> 45 at the time of enrolment.

You may not qualify if:

• Unable or unwilling to provide informed consent
• Contraindication to radionuclide bone scan
• Already diagnosed with PDB
• Spouse, partner or friend of case
• Not diagnosed with PDB
• No family history of PDB
• Participant willing and able to consent and comply with the study protocol.
• Age \> 45 at the time of enrolment
• Unable or unwilling to give informed consent

Sponsors & Collaborators

• University of Edinburgh: lead
• European Research Council: collaborator

Study Sites (1)

NHS Lothian

Edinburgh, EH4 2XU, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, saliva samples and stool samples will be collected from participants in the study.

MeSH Terms

Conditions

Osteitis Deformans

Condition Hierarchy (Ancestors)

Bone Diseases; Musculoskeletal Diseases

Study Officials

• Stuart Ralston

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2022
• First Posted: April 4, 2022
• Study Start: January 1, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

GB (1)