Clinical trial NCT03859895: Zoledronate In the Prevention of Paget's Disease: Long Term Extension
Official title: Zoledronate In the Prevention of Paget's Disease: Long Term Extension
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Paget Disease
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: European Research Council
First posted: 2019-03-01
Enrollment: 287
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients recruited to the ZiPP Trial (2008-005667-34)

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.

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

Primary outcomes:
measure: Primary Endpoint (former ZiPP interventional arm): The proportion of patients that develop PDB-like bone lesions
timeFrame: 5 year time-point
measure: Primary Endpoint (former ZiPP observational arm): proportion of individuals that develop abnormalities suggestive of PDB
timeFrame: During follow-up period
Secondary outcomes:
measure: 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.
timeFrame: 5 year time-point
measure: 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)).
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to SF36 (36-Item Short Form Survey) scores.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to HAQ (Health Assessment Questionnaire) scores.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to EQ5D (EuroQol five dimension scale) scores.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to IPAQ (International Physical Activity Questionnaire) scores.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to BPI (Brief Pain Inventory Scale) scores.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP interventional arm): Differences between ZiPP trial treatment and placebo groups with regard to development of PDB-related skeletal events (PRSE).
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using EQ5D.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using SF36.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using BPI.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using HAQ.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Health-related quality of life in ZiPP trial observational arm participants assessed using IPAQ.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using EQ5D.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using SF36.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using BPI.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using EQ5D.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using SF36.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using SF-36.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using BPI.
timeFrame: 5 year time-point
measure: Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using EQ5D.
timeFrame: 5 year time-point
Other outcomes:
Locations:
city: Geelong
country: Australia
facility: University Hospital Geelong
city: Nedlands
country: Australia
facility: Sir Charles Gardner Hospital
city: Newcastle
country: Australia
facility: Royal Newcastle Centre
city: Sydney
country: Australia
facility: University of Sydney
city: Toowoomba
country: Australia
facility: University of Queensland
city: Brussels
country: Belgium
facility: University Hospital Saint-Luc
city: Dublin
country: Ireland
facility: St. Vincent's University Hospital
city: Florence
country: Italy
facility: University Hospital of Careggi
city: Siena
country: Italy
facility: University of Siena
city: Turin
country: Italy
facility: University of Turin
city: Auckland
country: New Zealand
facility: University of Auckland
city: Christchurch
country: New Zealand
facility: The Princess Margaret Hospital
city: Barcelona
country: Spain
facility: Univeristy of Barcelona
city: Salamanca
country: Spain
facility: University Hospital of Salamanca
city: Bristol
country: United Kingdom
facility: University of Bristol
state: England
city: Liverpool
country: United Kingdom
facility: University of Liverpool
state: England
city: London
country: United Kingdom
facility: Guy's and St Thomas Hospital NHS Trust
state: England
city: London
country: United Kingdom
facility: King's College Hospital
state: England
city: Manchester
country: United Kingdom
facility: Manchester Royal Infirmary
state: England
city: Edinburgh
country: United Kingdom
facility: NHS Lothian
state: Scotland
city: Wrexham
country: United Kingdom
facility: Wrexham Maelor Hospital
state: Wales
Study officials:
affiliation: Univeristy of Edinburgh
name: Stuart Ralston, Prof
role: PRINCIPAL_INVESTIGATOR
References: