Paget DiseaseGAPDPDNCT05309954
Genetic Analysis to Predict the Development of Paget's Disease
An observational study of Paget Disease and Paget Disease of Bone, run by University of Edinburgh at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 years and olderHealthy volunteers can take part
- Conditions the study is for
- Paget Disease, Paget Disease of Bone
- How many people
- 135 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Jan 2022to 1 Jun 2031
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
- Spouse, partner or friend of case
- Not diagnosed with PDB
Show all 9Show fewer
- No family history of PDB
- Participant willing and able to consent and comply with the study protocol.
- Age > 45 at the time of enrolment
Who cannot join
- Unable or unwilling to provide informed consent
- Contraindication to radionuclide bone scan
- Already diagnosed with PDB
- Unable or unwilling to give informed consent
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Paget's disease of bone (PDB) is a common skeletal disorder characterised by increased bone turnover affecting one or more bones throughout the skeleton. The natural history of PDB is incompletely understood but it is clear that patients are often asymptomatic when the disease is at an early stage but that later in life when the patient presents clinically, irreversible skeletal damage is often present leading to various complications, some of which are irreversible. The most common symptom of PDB is bone pain which can be due to increased metabolic activity or complications such as bone deformity, secondary osteoarthritis, spinal stenosis and pathological fractures. Other complications include deafness due to involvement of the temporal bone and osteosarcoma which is rare but often fatal.
Genetic factors play an important role in PDB and people who have a family history of the disease in a first- degree relative have a seven-times increased risk of developing the disease as compared with controls. Part of the genetic risk for developing PDB is explained by inheritance of mutations in the SQSTM1 gene. Cross-sectional studies indicate that carriers of SQSTM1 mutations run a high risk of developing the disease with increasing age. However only 40% of people with a family history of PDB carry SQSTM1 mutations and current evidence suggests that the risk of PDB in people who do not carry SQSTM1 mutations is mediated by inheritance of other susceptibility alleles which individually have modest effects on the risk of developing PDB but which when combined, have additive effect on disease susceptibility. Environmental factors also play a role in PDB and in keeping with this a recent study has shown that epigenetic factors contribute to the pathogenesis of PDB and may have value as diagnostic markers for the risk of developing the disease.
It would be highly advantageous to be able to offer people with a family history of PDB a predictive test to give an indication of their personal risk of PDB. This would allow the disease to be picked up at an early stage before complications have occurred and for preventative treatment to be offered. Prevention is key since there is no evidence that treatment can prevent or reverse complications in people with established disease.
The aim of the present study is to try and identify genetic, epigenetic and other biomarkers for the development of PDB in people with a family history of the disorder in order to facilitate early diagnosis and treatment.
- Conditions
- Paget Disease, Paget Disease of Bone
- Medical subject headings
- Osteitis Deformans
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Measured: 5 years
Secondary outcomes (6)
Secondary Endpoint - Analysis of scores in SF36 (36-Item Short Form Survey)
SF-36 is a set of generic, coherent, and easily administered quality-of-life measures. Scoring is a two-step process. First, precoded numeric values are recoded per a scoring key. Note that all items are scored so that a high score defines a more favorable health state. In addition, each item is scored on a 0 to 100 range so that the lowest and highest possible scores are 0 and 100, respectively. Scores represent the percentage of total possible score achieved. In step 2, items in the same scale are averaged together to create a scale of scores.
Analyse the difference in scores between Participant and control groups with regard to SF36 (36-Item Short Form Survey) scores. Scores associated with Health-related quality of life, Depression, anxiety and pain will be analysed and compared between the two groups
Measured: 5 years
Secondary Endpoint- Analysis of scores in HAQ (Health Assessment Questionnaire)
the HAQ assesses a patient's level of functional ability and includes questions of fine movements of the upper extremity, locomotor activities of the lower extremity, and activities that involve both upper and lower extremities. There are 20 questions in eight categories of functioning which represent a comprehensive set of functional activities. The participant's responses are made on a scale from zero (no disability) to three (completely disabled).
Analyse the HAQ (Health Assessment Questionnaire) scores to determine if there is a differences between Participant and control groups. Scores associated with Health-related quality of life will be analysed and compared between the two groups
Measured: 5 years
Secondary Endpoint - Analysis of scores in EQ5D (EuroQol five dimension scale)
The EQ-5D-5L is a self-assessed, health related, quality of life questionnaire. The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. . Each level is rated on scale that describes the degree of problems in that area also has an overall health scale where the rater selects a number between 1-100 to describe the condition of their health, 100 being the best imaginable.
Analyse the EQ5D (EuroQol five dimension scale) scores to determine if there is a differences between Participant and control groups. Scores associated with Health-related quality of life, Depression, anxiety and pain will be analysed and compared between the two groups
Measured: 5 years
Secondary Endpoint - Analysis of scores in IPAQ (International Physical Activity Questionnaire)
The IPAQ form is an instrument designed primarily for population surveillance of physical activity among adults. IPAQ assesses physical activity undertaken across a comprehensive set of domains Continuous Score Expressed as MET-min per week: MET level x minutes of activity x events per week Sample Calculation MET levels MET-min/week for 30 min episodes, 5 times/week Walking = 3.3 METs 3.3*30*5 = 495 MET-min/week Moderate Intensity = 4.0 METs 4.0*30*5 = 600 MET-min/week Vigorous Intensity = 8.0 METs 8.0*30*5 = 1,200 MET-min/week ___________________________ TOTAL = 2,295 MET-min/week Total MET-min/week = (Walk METs*min*days) + (Mod METs*min*days) + Vig METs*min*days). A higher MET value would be indicative of more activity during that week.
Analyse the IPAQ scores to determine if there is a differences between Participant and control groups.
Measured: 5 years
Secondary Endpoint - Analysis of scores in BPI (Brief Pain Inventory Scale) scores.
The Brief Pain Inventory (BPI) is a self-administered assessment tool used in pain management. The BPI uses simple numeric rating scales (NRS) from 0 to 10, and the scale defines pain as follows: Score: 1 - 4 = Mild Pain, Score: 5 - 6 = Moderate Pain, Score: 7 - 10 = Severe Pain.
Analyse the BPI (Brief Pain Inventory Scale) scores to determine if there is a differences between Participant and control groups.
Measured: 5 years
Secondary Endpoint- Specialised Biomarker Analysis
Samples from both Participants and control group would be analysed for Specialised Biomarkers of Bone turnover (P1NP, BSALP, uNTx CTx). Activity of these markers will be analysed and compared between the two cohorts to determine if there is a difference and if it can be used a predictor
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2022
- Study start1 Jan 2022
- Primary completion30 Apr 2031 (estimated)
- Study completion1 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Paget DiseaseStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 135 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- European Research Council
- Responsible party
- Sponsor
- Investigators
- Stuart Ralston, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05309954
- Sponsor's protocol ID
- AC19056
- Other IDs
- 19/ES/0141, 259285
- Acronym
- GAPDPD
- Status last verified
- Jan 2026
- First submitted
- 11 Mar 2022
- Last updated
- 1 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Analysis to Predict the Development of Paget's Disease
- ClinicalTrials.gov ID
- NCT05309954
- Acronym / sponsor ID
- GAPDPD / AC19056
- Conditions
- Paget Disease, Paget Disease of Bone
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 135 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- European Research Council
- Study start
- 1 Jan 2022 (actual)
- Primary completion
- 30 Apr 2031 (estimated)
- Study completion
- 1 Jun 2031 (estimated)
- First posted
- 4 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Paget's disease of bone (PDB) is a common skeletal disorder characterised by increased bone turnover affecting one or more bones throughout the skeleton. The natural history of PDB is incompletely understood but it is clear that patients are often asymptomatic when the disease is at an early stage but that later in life when the patient presents clinically, irreversible skeletal damage is often present leading to various complications, some of which are irreversible. The most common symptom of PDB is bone pain which can be due to increased metabolic activity or complications such as bone deformity, secondary osteoarthritis, spinal stenosis and pathological fractures. Other complications include deafness due to involvement of the temporal bone and osteosarcoma which is rare but often fatal.
Genetic factors play an important role in PDB and people who have a family history of the disease in a first- degree relative have a seven-times increased risk of developing the disease as compared with controls. Part of the genetic risk for developing PDB is explained by inheritance of mutations in the SQSTM1 gene. Cross-sectional studies indicate that carriers of SQSTM1 mutations run a high risk of developing the disease with increasing age. However only 40% of people with a family history of PDB carry SQSTM1 mutations and current evidence suggests that the risk of PDB in people who do not carry SQSTM1 mutations is mediated by inheritance of other susceptibility alleles which individually have modest effects on the risk of developing PDB but which when combined, have additive effect on disease susceptibility. Environmental factors also play a role in PDB and in keeping with this a recent study has shown that epigenetic factors contribute to the pathogenesis of PDB and may have value as diagnostic markers for the risk of developing the disease.
It would be highly advantageous to be able to offer people with a family history of PDB a predictive test to give an indication of their personal risk of PDB. This would allow the disease to be picked up at an early stage before complications have occurred and for preventative treatment to be offered. Prevention is key since there is no evidence that treatment can prevent or reverse complications in people with established disease.
The aim of the present study is to try and identify genetic, epigenetic and other biomarkers for the development of PDB in people with a family history of the disorder in order to facilitate early diagnosis and treatment.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 45 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (9 listed)
- 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.
- Spouse, partner or friend of case
Key exclusion criteria (4 listed)
- Unable or unwilling to provide informed consent
- Contraindication to radionuclide bone scan
- Already diagnosed with PDB
- Unable or unwilling to give informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
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
Time frame: 5 years
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
Primary Endpoint (Participant arm): The proportion of patients that develop PDB-like bone lesions
Time frame: 5 years
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.
Primary Endpoint (Participant arm): T proportion of individuals that develop abnormalities suggestive of PDB
Time frame: 5 years
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
6 secondary outcomes
Secondary Endpoint - Analysis of scores in SF36 (36-Item Short Form Survey)
Time frame: 5 years
Secondary Endpoint- Analysis of scores in HAQ (Health Assessment Questionnaire)
Time frame: 5 years
Secondary Endpoint - Analysis of scores in EQ5D (EuroQol five dimension scale)
Time frame: 5 years
Secondary Endpoint - Analysis of scores in IPAQ (International Physical Activity Questionnaire)
Time frame: 5 years
Secondary Endpoint - Analysis of scores in BPI (Brief Pain Inventory Scale) scores.
Time frame: 5 years
Secondary Endpoint- Specialised Biomarker Analysis
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stuart Ralston principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Paget Disease and Paget Disease of Bone, run by University of Edinburgh at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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 (time frame: 5 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2026.