Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03859895
Recruitment Status : Recruiting
First Posted : March 1, 2019
Last Update Posted : October 15, 2019
Sponsor:
Collaborator:
European Research Council
Information provided by (Responsible Party):
University of Edinburgh

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.

Condition or disease
Paget Disease

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.

Layout table for study information
Study Type : Observational
Estimated Enrollment : 287 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Zoledronate In the Prevention of Paget's Disease: Long Term Extension
Actual Study Start Date : April 5, 2019
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Group/Cohort
Observational (without bone scan)
Former Observational Arm participants of the ZiPP trial.
Observational (with bone scan)
Former Interventional Arm participants of the ZiPP trial.



Primary Outcome Measures :
  1. 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.

  2. 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.


Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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.

  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using EQ5D. [ Time Frame: 5 year time-point ]
  15. Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using SF36. [ Time Frame: 5 year time-point ]
  16. Secondary Endpoint (former ZiPP observational arm): Pain in ZiPP trial observational arm participants assessed using BPI. [ Time Frame: 5 year time-point ]
  17. Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using EQ5D. [ Time Frame: 5 year time-point ]
  18. Secondary Endpoint (former ZiPP observational arm): Anxiety in ZiPP trial observational arm participants assessed using SF36. [ Time Frame: 5 year time-point ]
  19. Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using SF-36. [ Time Frame: 5 year time-point ]
  20. Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using BPI. [ Time Frame: 5 year time-point ]
  21. Secondary Endpoint (former ZiPP observational arm): Depression in ZiPP trial observational arm participants assessed using EQ5D. [ Time Frame: 5 year time-point ]

Biospecimen Retention:   Samples With DNA
Blood samples, saliva samples and stool samples will be collected from participants in the study.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients recruited to the ZiPP Trial (2008-005667-34)
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03859895


Contacts
Layout table for location contacts
Contact: Elaine Kinsella, PhD 01316519916 ZIPP-LTE@ed.ac.uk
Contact: Phillip Rayson 01316519928 ZIPP-LTE@ed.ac.uk

Locations
Show Show 21 study locations
Sponsors and Collaborators
University of Edinburgh
European Research Council
Investigators
Layout table for investigator information
Principal Investigator: Stuart Ralston, Prof Univeristy of Edinburgh
Layout table for additonal information
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT03859895    
Other Study ID Numbers: AC18051
245197 ( Other Identifier: IRAS (Integrated Research Application System) )
18/ES/0086 ( Other Identifier: Research Ethics Committee (EoSRES) )
First Posted: March 1, 2019    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No