Paget DiseaseZiPP-LTENCT03859895
Zoledronate In the Prevention of Paget's Disease: Long Term Extension
An observational study of Paget Disease, run by University of Edinburgh at 21 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Paget Disease
- How many people
- 287 participants
- Where
- 21 sitesin 7 countries
- Study dates
- 5 Apr 2019to May 2027
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients recruited to the ZiPP Trial (2008-005667-34)
Who may be able to join
- Subject that participated in ZiPP
- Participant willing and able to consent and comply with the study protocol.
Who cannot join
- Unable or unwilling to provide informed consent
Trial locations and contacts
21 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
21 sites in 7 countries
United Kingdom7 sites
University of Bristol
Bristol, England, BC10 5NB
NHS Lothian
Edinburgh, Scotland, EH4 2XU
University of Liverpool
Liverpool, England, L7 8XP
Guy's and St Thomas Hospital NHS Trust
London, England, SE1 9RT
King's College Hospital
London, England, SE5 9RS
Manchester Royal Infirmary
Manchester, England, M13 9WL
Wrexham Maelor Hospital
Wrexham, Wales, LL13 7TD
Australia5 sites
University Hospital Geelong
Geelong, 3220
Sir Charles Gardner Hospital
Nedlands, 6009
Royal Newcastle Centre
Newcastle, NSW 2305
University of Sydney
Sydney
University of Queensland
Toowoomba, QLD 4350
Italy3 sites
University Hospital of Careggi
Florence, 50139
University of Siena
Siena, 53100
University of Turin
Turin, 10126
New Zealand2 sites
University of Auckland
Auckland, 92019
The Princess Margaret Hospital
Christchurch, 731 8022
Spain2 sites
Univeristy of Barcelona
Barcelona
University Hospital of Salamanca
Salamanca, 37007
About this study
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.
Read the 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
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 (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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)).
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
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.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using EQ5D.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using SF36.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using BPI.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using HAQ.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using IPAQ.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using EQ5D.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using SF36.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using BPI.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using EQ5D.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using SF36.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using SF-36.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using BPI.
Measured: 5 year time-point
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using EQ5D.
Measured: 5 year time-point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start5 Apr 2019
- Primary completionDec 2026 (estimated)
- Study completionMay 2027 (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
- 287 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- European Research Council
- Responsible party
- Sponsor
- Investigators
- Stuart Ralston, Prof, Principal investigator, Univeristy of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03859895
- Sponsor's protocol ID
- AC18051
- Other IDs
- 245197, 18/ES/0086
- Acronym
- ZiPP-LTE
- Status last verified
- Feb 2026
- First submitted
- 31 Jan 2019
- Last updated
- 17 Feb 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 17 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Zoledronate In the Prevention of Paget's Disease: Long Term Extension
- ClinicalTrials.gov ID
- NCT03859895
- Acronym / sponsor ID
- ZiPP-LTE / AC18051
- Conditions
- Paget Disease
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 287 participants (estimated)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- European Research Council
- Study start
- 5 Apr 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 1 Mar 2019 (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 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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Observational (without bone scan) | – | –Former Observational Arm participants of the ZiPP trial. |
| Observational (with bone scan) | – | –Former Interventional Arm participants of the ZiPP trial. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients recruited to the ZiPP Trial (2008-005667-34)
Key inclusion criteria (2 listed)
- Subject that participated in ZiPP
- Participant willing and able to consent and comply with the study protocol.
Key exclusion criteria (1 listed)
- Unable or unwilling to provide 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 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.
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.
21 secondary outcomes
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
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
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
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
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
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
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
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
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
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
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
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
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
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using EQ5D.
Time frame: 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
Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using BPI.
Time frame: 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
Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using SF36.
Time frame: 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
Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using BPI.
Time frame: 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
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 17 Feb 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Paget Disease
RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Active, not recruitingPhase 2
Combination Chemotherapy With or Without Trastuzumab in Treating Patients With Stage II or Stage III Breast Cancer
Breast Cancer
Active, not recruitingPhase 2
Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers
Anaplastic Large Cell Lymphoma, ALK-Negative, Anaplastic Large Cell Lymphoma, ALK-Positive
RecruitingPhase 1
A Study of MQ710 With and Without Pembrolizumab in People With Solid Tumor Cancer
Cutaneous Squamous Cell Carcinoma, SCC - Squamous Cell Carcinoma
Active, not recruitingObservational study
Genetic Analysis to Predict the Development of Paget's Disease
Paget Disease, Paget Disease of Bone
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.
Stuart Ralston, Prof principal investigator
Univeristy of Edinburgh
21 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Paget Disease, run by University of Edinburgh at 21 sites in 7 countries.
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 2 inclusion and 1 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: enrolling by invitation, as of the sponsor's last update on 17 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United Kingdom, Australia, Italy, New Zealand, Spain and 2 more countries. 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 Endpoint (former ZiPP interventional arm): The proportion of patients that develop PDB-like bone lesions (time frame: 5 year time-point). The study lists 2 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 17 Feb 2026.