ISRCTN11616770.

Trial name or title	Zoledronate in the Prevention of Paget's: the ZiPP study
Methods	Multisite double blind placebo controlled randomised trial. Two sub‐studies: Interventional: To determine if targeted intervention with zoledronate can prevent the development of raised bone turnover and/or focal bone lesions in subjects who are genetically predisposed to develop Paget's disease of bone (PDB) because they carry mutations in SQSTM1 that have previously been associated with PDB. Observational: To determine if a genetic test cause increased anxiety and depression, even if found not to have the SQSTM1 gene mutation and to determine if there is any difference in the biochemical makers which are predictive of the disease in patients without SQSTM1 gene mutation group compared to the group who have the mutation. Follow up: 5 years.
Participants	Participant inclusion criteria Interventional study: Relatives of patients with SQSTM1 mutations, aged 30 years old or greater, who carry SQSTM1 mutations and who have not already diagnosed with PDB at study entry Observational study: Relatives of patients with SQSTM1 mutations, aged between 30 years old or greater who on screening are found NOT to have SQSTM1 mutations Countries of recruitment: Australia, Belgium, Ireland, Italy, Spain, United Kingdom.
Interventions	Interventional study: Participants will be randomised to either infusions of zoledronate (Aclasta®) 5 mg by intravenous infusion over 15 minutes or placebo (0.9% saline) at baseline.
Outcomes	Interventional study: Primary outcome: Total number of subjects who develop new bone lesions between the baseline visit and the final follow up visit. Observational study: Primary outcome: Anxiety/depression, measured using the HADS scale. Both studies: Secondary outcomes: 1. Development of elevated bone turnover, as measured by alkaline phosphatase and other biochemical markers of bone turnover. 2. Quality of life, and anxiety and depression assessed by the SF‐36, BPI and HADS questionnaires.
Starting date	12/01/2009
Contact information	Mr Adam Wilson Clinical Trials Manager e‐mail: zipptri1@exseed.ed.ac.uk
Ending date	31/01/2020
Target number of participants	Intervention study: 188 participants Observational study: 125 participants
Identifier	ISRCTN11616770 DOI 10.1186/ISRCTN11616770
Notes	Sponsor information: University of Edinburgh (UK) Funder name: Medical Research Council (MRC) (UK) (ref: G0701625; 85281)