- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03859895
Zoledronate In the Prevention of Paget's Disease: Long Term Extension (ZiPP-LTE)
November 28, 2023 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
Enrolling by invitation
Conditions
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
Observational
Enrollment (Estimated)
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
- Name: Jonathan Phillips, PhD
- Phone Number: 07773309603
- Email: ZIPP-LTE@ed.ac.uk
Study Contact Backup
- Name: Berg Kathryn
- Email: ZIPP-LTE@ed.ac.uk
Study Locations
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Geelong, Australia, 3220
- University Hospital Geelong
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Nedlands, Australia, 6009
- Sir Charles Gardner Hospital
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Newcastle, Australia, NSW 2305
- Royal Newcastle Centre
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Sydney, Australia
- University of Sydney
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Toowoomba, Australia, QLD 4350
- University of Queensland
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Brussels, Belgium
- University Hospital Saint-Luc
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Dublin, Ireland
- St. Vincent's University Hospital
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Florence, Italy, 50139
- University Hospital of Careggi
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Siena, Italy, 53100
- University of Siena
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Turin, Italy, 10126
- University of Turin
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Auckland, New Zealand, 92019
- University of Auckland
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Christchurch, New Zealand, 731 8022
- The Princess Margaret Hospital
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Barcelona, Spain
- Univeristy of Barcelona
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Salamanca, Spain, 37007
- University Hospital of Salamanca
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England
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Bristol, England, United Kingdom, BC10 5NB
- University of Bristol
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Liverpool, England, United Kingdom, L7 8XP
- University of Liverpool
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London, England, United Kingdom, SE5 9RS
- King's College Hospital
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London, England, United Kingdom, SE1 9RT
- Guy's and St Thomas Hospital NHS Trust
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Manchester, England, United Kingdom, M13 9WL
- Manchester Royal Infirmary
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Scotland
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Edinburgh, Scotland, United Kingdom, EH4 2XU
- NHS Lothian
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Wales
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Wrexham, Wales, United Kingdom, LL13 7TD
- Wrexham Maelor Hospital
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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
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 |
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Observational (without bone scan)
Former Observational Arm participants of the ZiPP trial.
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Observational (with bone scan)
Former Interventional Arm participants of the ZiPP trial.
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What is the study measuring?
Primary Outcome Measures
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
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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.
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5 year time-point
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Primary Endpoint (former ZiPP observational arm): proportion of individuals that develop abnormalities suggestive of PDB
Time Frame: During follow-up period
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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.
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During follow-up period
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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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.
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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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
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using SF36.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using BPI.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using SF36.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using SF-36.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using BPI.
Time Frame: 5 year time-point
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5 year time-point
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Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using EQ5D.
Time Frame: 5 year time-point
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5 year time-point
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- 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)
April 5, 2019
Primary Completion (Estimated)
December 1, 2024
Study Completion (Estimated)
December 1, 2024
Study Registration Dates
First Submitted
January 31, 2019
First Submitted That Met QC Criteria
February 28, 2019
First Posted (Actual)
March 1, 2019
Study Record Updates
Last Update Posted (Actual)
November 29, 2023
Last Update Submitted That Met QC Criteria
November 28, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Other Study ID 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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