Zoledronate In the Prevention of Paget's Disease: Long Term Extension

NCT03859895 | Enrolling By Invitation

• 3 other identifiers: AC1805124519718/ES/0086
• Study Type: observational
• Target: 287
• Locations: 7 countries
• Sites: 21

Brief Summary

Paget's disease of the bone (PDB) is a metabolic bone disorder which in some individuals can cause pain, bone deformity, arthritis and deafness, although in many patients it does not cause symptoms. Paget's disease has a strong genetic component and SQSTM1 is the most important susceptibility gene. People who inherit mutations in SQSTM1 have a high risk of developing PDB later in life. This study is an extension of the ZiPP (Zoledronate in the Prevention of Paget's) study which was is randomised trial currently in progress to determine if the bisphosphonate zoledronic acid (ZA) can prevent or delay the development of PDB-like bone lesions compared with a dummy treatment (placebo) in people who inherit SQSMT1 gene mutations. Although the ZiPP study will provide information on whether early ZA treatment can favourably influence bone lesion development the significance of this to the patient in terms of symptoms is unclear as yet. The aim of the extension study is to keep these individuals under surveillance for any symptoms or signs of PDB over a further 5 year period and to evaluate if there has been any progression of PDB-like lesions by bone scan at the end of this period.

Conditions

Paget Disease

Outcome Measures

Primary Outcomes (2)

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

  The proportion of patients in each of the randomisation groups that develop PDB-like bone lesions by the end of study assessed by radionuclide bone scan.

  5 year time-point

• Primary Endpoint (former ZiPP observational arm): 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 10-year duration of follow up.

  During follow-up period

Secondary Outcomes (21)

• Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to the number of new bone lesions assessed by radionuclide bone scan.

  5 year time-point

• Secondary Endpoint (former ZiPP interventional arm): Evaluate differences between ZiPP treatment and placebo groups for change in bone lesion activity by semi-quantitative analysis of radionuclide bone scans (method described by Patel et al (1995)).

  5 year time-point

• Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to SF36 (36-Item Short Form Survey) scores.

  5 year time-point

• Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to HAQ (Health Assessment Questionnaire) scores.

  5 year time-point

• Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to EQ5D (EuroQol five dimension scale) scores.

  5 year time-point

Study Arms (2)

Observational (without bone scan)

Former Observational Arm participants of the ZiPP trial.

Observational (with bone scan)

Former Interventional Arm participants of the ZiPP trial.

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients recruited to the ZiPP Trial (2008-005667-34)

You may qualify if:

• Subject that participated in ZiPP
• Participant willing and able to consent and comply with the study protocol.

You may not qualify if:

• Unable or unwilling to provide informed consent

Sponsors & Collaborators

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

Study Sites (21)

University Hospital Geelong

Geelong, 3220, Australia

Location

Sir Charles Gardner Hospital

Nedlands, 6009, Australia

Location

Royal Newcastle Centre

Newcastle, NSW 2305, Australia

Location

University of Sydney

Sydney, Australia

Location

University of Queensland

Toowoomba, QLD 4350, Australia

Location

University Hospital Saint-Luc

Brussels, Belgium

Location

St. Vincent's University Hospital

Dublin, Ireland

Location

University Hospital of Careggi

Florence, 50139, Italy

Location

University of Siena

Siena, 53100, Italy

Location

University of Turin

Turin, 10126, Italy

Location

University of Auckland

Auckland, 92019, New Zealand

Location

The Princess Margaret Hospital

Christchurch, 731 8022, New Zealand

Location

Univeristy of Barcelona

Barcelona, Spain

Location

University Hospital of Salamanca

Salamanca, 37007, Spain

Location

University of Bristol

Bristol, England, BC10 5NB, United Kingdom

Location

University of Liverpool

Liverpool, England, L7 8XP, United Kingdom

Location

Guy's and St Thomas Hospital NHS Trust

London, England, SE1 9RT, United Kingdom

Location

King's College Hospital

London, England, SE5 9RS, United Kingdom

Location

Manchester Royal Infirmary

Manchester, England, M13 9WL, United Kingdom

Location

NHS Lothian

Edinburgh, Scotland, EH4 2XU, United Kingdom

Location

Wrexham Maelor Hospital

Wrexham, Wales, LL13 7TD, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

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

Study Officials

• Stuart Ralston, Prof

  Univeristy 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: January 31, 2019
• First Posted: March 1, 2019
• Study Start: April 5, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

BE (1); IE (1); AU (5); GB (7); NZ (2); ES (2); IT (3)