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

NCT ID: NCT03859895

Last Updated: 2025-02-14

Basic Information

• Recruitment Status: ENROLLING_BY_INVITATION
• Total Enrollment: 287 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-04-05
• Study Completion Date: 2027-05-31

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.

Detailed Description

It is at present unclear whether intervention with bisphosphonates is of clinical benefit in early PDB. Although the ZiPP study is expected to provide information on whether ZA can favourably influence the development of bone lesions characteristic of early PDB as determined by radionuclide bone scan imaging, longer term follow up is required to determine if this will translate into clinical benefit. The extension study described here will provide new information on the natural history of PDB by follow up of people that took part in the ZIPP trial. Although the ZIPP-LTE study is an observational study, treatment for PDB may be given to participants according to normal clinical practice if they develop signs or symptoms of PDB during the extension. Treatment will therefore be offered to all participants that develop symptoms of PDB during follow up. Additionally, subjects that were previously been exposed to ZA in the core study will also be offered further ZA or another bisphosphonate licensed for PDB if they develop evidence of increased metabolic activity thought to be due to PDB, even if asymptomatic. The reason for this is that adverse effects are rare in patients who have previously been treated with ZA but are common on first exposure to ZA. Both therapeutic approaches are commonly used in patients with early PDB with no evidence that one is superior to another. In addition to providing information on the natural history of PDB, part of the aim of the extension will be to evaluate the risks and benefits of these two approaches to standard care of in terms of new lesion development, pain, quality of life and adverse events in the context of people who inherit SQSTM1 mutations.

Conditions

Paget Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Observational (without bone scan)

Former Observational Arm participants of the ZiPP trial.

No interventions assigned to this group

Observational (with bone scan)

Former Interventional Arm participants of the ZiPP trial.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

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

Exclusion Criteria

• Unable or unwilling to provide informed consent

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

European Research Council

OTHER

Sponsor Role: collaborator

University of Edinburgh

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stuart Ralston, Prof

Role: PRINCIPAL_INVESTIGATOR

Univeristy of Edinburgh

Locations

University Hospital Geelong

Geelong, , Australia

Sir Charles Gardner Hospital

Nedlands, , Australia

Royal Newcastle Centre

Newcastle, , Australia

University of Sydney

Sydney, , Australia

University of Queensland

Toowoomba, , Australia

University Hospital Saint-Luc

Brussels, , Belgium

St. Vincent's University Hospital

Dublin, , Ireland

University Hospital of Careggi

Florence, , Italy

University of Siena

Siena, , Italy

University of Turin

Turin, , Italy

University of Auckland

Auckland, , New Zealand

The Princess Margaret Hospital

Christchurch, , New Zealand

Univeristy of Barcelona

Barcelona, , Spain

University Hospital of Salamanca

Salamanca, , Spain

University of Bristol

Bristol, England, United Kingdom

University of Liverpool

Liverpool, England, United Kingdom

Guy's and St Thomas Hospital NHS Trust

London, England, United Kingdom

King's College Hospital

London, England, United Kingdom

Manchester Royal Infirmary

Manchester, England, United Kingdom

NHS Lothian

Edinburgh, Scotland, United Kingdom

Wrexham Maelor Hospital

Wrexham, Wales, United Kingdom

Countries

Australia; Belgium; Ireland; Italy; New Zealand; Spain; United Kingdom

Other Identifiers

245197

Identifier Type: OTHER

Identifier Source: secondary_id

18/ES/0086

Identifier Type: OTHER

Identifier Source: secondary_id

AC18051

Identifier Type: -

Identifier Source: org_study_id