Zoledronate in the Prevention of Paget's Disease (ZiPP)
Research type
Research Study
Full title
Randomised trial of genetic testing and targeted Zoledronic acid therapy to prevent SQSTM1 mediated Paget's disease.
IRAS ID
3584
Contact name
Stuart Ralston
Contact email
Sponsor organisation
University of Edinburgh
Eudract number
2008-005667-34
ISRCTN Number
ISRCTN11616770
Research summary
Summary of Research
Paget disease of bone (PDB) is a serious bone disease which causes pain, arthritis and deafness and which can cause extreme bone deformity. Up to 40% of patients with the PDB have inherited it from family members and a mutation in the SQSTM1 gene is an important cause of the disease. Patients who have the SQSTM1 gene usually develop severe PDB. Paget's disease can be treated with drugs called bisphosphonates but often the disease has caused irreversible damage to the bones before these drugs are prescribed. The aim of this research is to find out if better results can be obtained by giving early treatment to people who are genetically at risk of getting the disease because of the SQSTM1 gene, but who have not yet developed it. We will do this by carrying out genetic tests on people with a family history of PDB to see if they have the SQSTM1 gene. People who are found to carry the gene will be invited to take part in a study which 50% will be given an active treatment and 50% will be given a dummy treatment. We will then follow both groups of people for 5 years and compare the results at the end of this time. We will carry out special bone scans to see if people in the trial have developed bone abnormalities characteristic of the disease and to see if the active treatment has prevented this to any extent. Blood and urine samples will be analysed for biochemical markers of bone turnover, an extremely sensitive test for detecting early signs of the disease. This could help prevent the development of the serious complications that can occur in PDB and improve the outlook for people who have a family history of the disease.Summary of Results
We recruited 222 individuals of whom 111 were randomised to ZA and 111 to placebo. A total of 180 individuals (80.6%) completed the study after a median of 84 months (range 0-127). At baseline, 21/222 individuals (9.5%) had radionuclide bone scan evidence of PDB. Two participants in the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight participants in the placebo group had a poor outcome (lesions which were new, unchanged, or progressing) compared with none in the ZA group (OR =0.08, 95% CI 0.00-0.42, p=0.003). In the ZA group 13/15 lesions present at the start had disappeared compared with 1/29 lesions that disappeared in the placebo group. (p<0.0001, between groups). One participant allocated to placebo required rescue therapy with ZA because of a PDRSE. Significant reductions were observed for serum CTX (p<0.0001), adjusted ALP (p=0.032), bone specific ALP (p=0.0003) and PINP (p<0.0001) in the ZA group. The number and type of adverse events and serious adverse events did not differ between groups.Conclusions
A single infusion of ZA has favourable effects on the progression of early PDB in SQSTM1 mutation carriers.REC name
East of Scotland Research Ethics Service REC 2
REC reference
08/S0501/84
Date of REC Opinion
22 Dec 2008
REC opinion
Further Information Favourable Opinion