A research study to determine if a drug called Zoledronic Acid prevents a serious bone disease (Paget's disease) in people who are known to have a change in a gene which has been linked to the disease.

Randomised Trial of Genetic Testing and Targeted Zoledronic acid therapy to Prevent SQSTM1 Mediated Paget's Disease (Zoledronate in the Prevention of Paget's). - ZiPP study

Status

Active, not recruiting

Phases

Phase 4

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2008-005667-34-BE

Enrollment

357

Registered

2010-10-06

Start date

2010-11-15

Completion date

Unknown

Last updated

2025-02-03

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Paget's disease of the bone (PDB) MedDRA version: 21.1 Level: LLT Classification code 10033363 Term: Paget's disease of bone System Organ Class: 100000004859

Interventions

Trade Name: Aclasta Product Name: Aclasta Pharmaceutical Form: Solution for infusion INN or Proposed INN: Zoledronic Acid CAS Number: 165800-06-6 Other descriptive name: ZOLEDRONIC ACID MONOHYDRATE Co

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion criteria for a Genetic Test - Patients with PDB (Probands): Probands must be diagnosed with PDB AND Have at least one relative aged 30 years old or greater Inclusion criteria for a Genetic Test - Relatives: Relatives are aged 30 years old or greater. Relatives not yet been diagnosed with PDB. Inclusion Criteria for the Intervention Study: Relatives of patients with SQSTM1 mutations aged 30 years old or greater who carry SQSTM1 mutations. Not already diagnosed with PDB at study entry. Inclusion Criteria for the Observational Study: Relatives aged between 30 years old or greater Relatives who on screening are found NOT to have SQSTM1 mutations Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 194 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 63

Exclusion criteria

Exclusion criteria: Exclusion Criteria for Genetic Test (Patient with PDB and Relatives) Subjects not willing to have a blood sample taken. Subjects who are unwilling or unable to consent. Exclusion Criteria for the Intervention Study Already diagnosed with PDB. Unwilling or unable to consent. Bisphosphonates contraindicated. Receiving bisphosphonate therapy for another reason. Osteonecrosis of the jaw (ONJ). Estimated GFR (eGFR) < 35ml/min. Hypocalcaemia Metastatic cancer or cancer diagnosed less than 2 years ago where treatment is still ongoing. Active uveitis, iritis, or episcleritis. Already taking part in another randomised controlled clinical trial. Pregnancy. Lactation. Exclusion waivers will not be permitted. 1 Female patients of child bearing potential should have a negative pregnancy test on the day of, or the day before, the infusion of study drug. The preferred method of testing for pregnancy is serum beta-hCG, but a urine beta-hCG is also acceptable for centres that are unable to obtain a serum beta-hCG within 1-2 days. Participants who are sexually active must receive specific advice about the possible risks associated with getting pregnant whilst on the trial and must agree to practice a medically acceptable form of birth control for at least 12 months post infusion (acceptable birth control defined as the use of an IUD, a barrier method with spermicide, condoms, subdermal implant or oral contraceptives) Exclusion Criteria for the Observational Study Subjects diagnosed with PDB or SQSTM1 mutation positive

Design outcomes

Primary

Measure	Time frame
Main Objective: To determine whether targeted intervention with Zoledronic acid can prevent the development of new focal bone lesions in carriers of SQSTM1 gene mutations. There will be an observational group in this study who have the same risk of developing paget's disease as the general population. The primary objective of the Observational study will be to determine if genetic testing impacts on quality of life or depression in participants who do not have SQSTM1 gene mutations.;Secondary Objective: The secondary objectives of the study will be to determine whether targeted intervention with Zoledronic acid: a) can modify the activity of existing bone lesions in carriers of SQSTM1 gene mutations, b) can reduce or prevent PDB-related skeletal events (PRSE) in carriers of SQSTM1 mutations. c) can reduce or prevent increases in bone turnover in carriers of SQSTM1 gene mutations. d) can modify quality of life, bone pain and anxiety or depression. For the observational study, the secondary objectives will be to determine if: a) bone turnover changes with time in non-gene carriers, b) alterations in the quality of life occur in non-gene carriers.;Primary end point(s): In the intervention study, the primary outcome will be the total number of subjects who develop new bone lesions on radionuclide bone scans with the characteristics of PDB between the baseline visit and the final follow up visit. The presence of lesions will be assessed by an imaging expert blinded to treatment allocation. A new bone lesion will be defined as evidence of involvement of a new bone or part of an existing bone at the end-of-study visit which was not thought to be involved at the baseline visit”. In the observational study, the primary outcome measure will be anxiety / depression, measured using the HADS scale.;Timepoint(s) of evaluation of this end point: The primary outcomes will be assessed following the final follow up visit for the last patient.	—

Measure

Time frame

Main Objective: To determine whether targeted intervention with Zoledronic acid can prevent the development of new focal bone lesions in carriers of SQSTM1 gene mutations. There will be an observational group in this study who have the same risk of developing paget's disease as the general population. The primary objective of the Observational study will be to determine if genetic testing impacts on quality of life or depression in participants who do not have SQSTM1 gene mutations.;Secondary Objective: The secondary objectives of the study will be to determine whether targeted intervention with Zoledronic acid: a) can modify the activity of existing bone lesions in carriers of SQSTM1 gene mutations, b) can reduce or prevent PDB-related skeletal events (PRSE) in carriers of SQSTM1 mutations. c) can reduce or prevent increases in bone turnover in carriers of SQSTM1 gene mutations. d) can modify quality of life, bone pain and anxiety or depression. For the observational study, the secondary objectives will be to determine if: a) bone turnover changes with time in non-gene carriers, b) alterations in the quality of life occur in non-gene carriers.;Primary end point(s): In the intervention study, the primary outcome will be the total number of subjects who develop new bone lesions on radionuclide bone scans with the characteristics of PDB between the baseline visit and the final follow up visit. The presence of lesions will be assessed by an imaging expert blinded to treatment allocation. A new bone lesion will be defined as evidence of involvement of a new bone or part of an existing bone at the end-of-study visit which was not thought to be involved at the baseline visit”. In the observational study, the primary outcome measure will be anxiety / depression, measured using the HADS scale.;Timepoint(s) of evaluation of this end point: The primary outcomes will be assessed following the final follow up visit for the last patient.

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Secondary

Measure	Time frame
Secondary end point(s): In the interventional study, the secondary outcome measures will be: a) number of new bone lesions on radionuclide bone scan, b) change in activity of existing bone lesions that were present at the baseline assessed by semiquantitative analysis of radionuclide bone scans, c) the development of PDB-related skeletal events (PRSE) in carriers of SQSTM1 mutations, defined as any one of the following: - development of new bone lesions thought to be due to PDB on imaging - development of complications thought to be due to the development or progression of PDB including pathological fractures, bone deformity, deafness, deafness, joint replacement surgery or other orthopaedic procedures - administration of treatment for PDB with an antiresorptive drug because of the development of signs or symptoms thought to be due to PDB such as pain localised to an affected site or neurological symptoms d) the development of increased bone turnover, as assessed by measurement of biochemical markers of bone resorption (NTX) and bone formation (ALP, BSALP, P1NP), e) quality of life, and anxiety and depression assessed by the SF-36, BPI and HADS questionnaires, f) presence and severity of localised bone pain as assessed by the BPI pain manikin, g) presence and severity of pain assessed by the BPI pain questionnaire. In the observational study, the secondary outcomes will be: a) the development of increased bone turnover, as assessed by measurement of biochemical markers of bone resorption (NTX) and bone formation (ALP, BSALP, P1NP), b) quality of life, assessed by the SF-36 questionnaire.;Timepoint(s) of evaluation of this end point: The secondary outcomes will be assessed following the final follow up visit for the last patient.	—

Measure

Time frame

Secondary end point(s): In the interventional study, the secondary outcome measures will be: a) number of new bone lesions on radionuclide bone scan, b) change in activity of existing bone lesions that were present at the baseline assessed by semiquantitative analysis of radionuclide bone scans, c) the development of PDB-related skeletal events (PRSE) in carriers of SQSTM1 mutations, defined as any one of the following: - development of new bone lesions thought to be due to PDB on imaging - development of complications thought to be due to the development or progression of PDB including pathological fractures, bone deformity, deafness, deafness, joint replacement surgery or other orthopaedic procedures - administration of treatment for PDB with an antiresorptive drug because of the development of signs or symptoms thought to be due to PDB such as pain localised to an affected site or neurological symptoms d) the development of increased bone turnover, as assessed by measurement of biochemical markers of bone resorption (NTX) and bone formation (ALP, BSALP, P1NP), e) quality of life, and anxiety and depression assessed by the SF-36, BPI and HADS questionnaires, f) presence and severity of localised bone pain as assessed by the BPI pain manikin, g) presence and severity of pain assessed by the BPI pain questionnaire. In the observational study, the secondary outcomes will be: a) the development of increased bone turnover, as assessed by measurement of biochemical markers of bone resorption (NTX) and bone formation (ALP, BSALP, P1NP), b) quality of life, assessed by the SF-36 questionnaire.;Timepoint(s) of evaluation of this end point: The secondary outcomes will be assessed following the final follow up visit for the last patient.

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Countries

Australia, Belgium, Ireland, Italy, New Zealand, Spain, United Kingdom

Contacts

Public ContactAnna Heye

Edinburgh Clinical Trials Unit

zipptri1@exseed.ed.ac.uk+441316519917

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026