Zoledronate In the Prevention of Paget's Disease: Long Term Extension (ZiPP-LTE)

February 12, 2026 updated by: University of Edinburgh
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
287

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Australia
      • Geelong, Australia, 3220
        • University Hospital Geelong
      • Nedlands, Australia, 6009
        • Sir Charles Gardner Hospital
      • Newcastle, Australia, NSW 2305
        • Royal Newcastle Centre
      • Sydney, Australia
        • University of Sydney
      • Toowoomba, Australia, QLD 4350
        • University of Queensland
  • Belgium
      • Brussels, Belgium
        • University Hospital Saint-Luc
  • Ireland
      • Dublin, Ireland
        • St. Vincent'S University Hospital
  • Italy
      • Florence, Italy, 50139
        • University Hospital of Careggi
      • Siena, Italy, 53100
        • University of Siena
      • Turin, Italy, 10126
        • University of Turin
  • New Zealand
      • Auckland, New Zealand, 92019
        • University of Auckland
      • Christchurch, New Zealand, 731 8022
        • The Princess Margaret Hospital
  • Spain
      • Barcelona, Spain
        • Univeristy of Barcelona
      • Salamanca, Spain, 37007
        • University Hospital of Salamanca
  • United Kingdom
    • England
      • Bristol, England, United Kingdom, BC10 5NB
        • University of Bristol
      • Liverpool, England, United Kingdom, L7 8XP
        • University of Liverpool
      • London, England, United Kingdom, SE5 9RS
        • King's College Hospital
      • London, England, United Kingdom, SE1 9RT
        • Guy's and St Thomas Hospital NHS Trust
      • Manchester, England, United Kingdom, M13 9WL
        • Manchester Royal Infirmary
    • Scotland
      • Edinburgh, Scotland, United Kingdom, EH4 2XU
        • NHS Lothian
    • Wales
      • Wrexham, Wales, United Kingdom, LL13 7TD
        • Wrexham Maelor 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Observational (without bone scan)
Former Observational Arm participants of the ZiPP trial.
Observational (with bone scan)
Former Interventional Arm participants of the ZiPP trial.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Primary Endpoint (former ZiPP interventional arm): The proportion of patients that develop PDB-like bone lesions
Time Frame: 5 year time-point
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
Time Frame: During follow-up period
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 5 year time-point
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)).
Time Frame: 5 year time-point
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.
Time Frame: 5 year time-point
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.
Time Frame: 5 year time-point
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.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to IPAQ (International Physical Activity Questionnaire) scores.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to BPI (Brief Pain Inventory Scale) scores.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to development of PDB-related skeletal events (PRSE).
Time Frame: 5 year time-point
Defined as new bone lesions thought to be due to PDB on imaging OR complications of PDB such as pathological fractures, bone deformity, deafness, and joint replacement surgery OR administration of treatment for PDB because of pain localised to an affected site in a patient with metabolically active disease.
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using SF36.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using BPI.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using HAQ.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using IPAQ.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using SF36.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using BPI.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using SF36.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using SF-36.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using BPI.
Time Frame: 5 year time-point
5 year time-point
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
5 year time-point

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Edinburgh

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
European Research Council

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stuart Ralston, Prof, Univeristy of Edinburgh

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 5, 2019

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 31, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 28, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 1, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 17, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2026

More Information

Terms related to this study

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • AC18051
  • 245197 (Other Identifier: IRAS (Integrated Research Application System))
  • 18/ES/0086 (Other Identifier: Research Ethics Committee (EoSRES))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

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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