Trial of Ondansetron as a Parkinson’s HAllucinations Treatment
Parkinson's hallucinations
The intervention will consist of flexible dosing of ondansetron/placebo (8-24mg/day) as a treatment for Parkinson’s hallucinations, with a 12-week primary outcome and follow-up to 24 weeks. The treatment dose will increase from a single daily 8 mg tablet (AM) (weeks 1 and 2), to 16 mg/day (8 mg twice daily) (weeks 3 and 4), with a further increase to 24 mg/day (8 mg AM, 16 mg PM) (weeks 5 and 6). The study will recruit people with Parkinson's, aged over 55 years, who are experiencing hallucinations at least weekly, at a point when other approaches to treatment (altering lighting, reducing Parkinson's medication) have failed. Those taking part will be allocated (randomly via a computerized system) to receive drug or placebo and neither the prescribing clinicians or participants will know which treatment they are taking. The dose of the study drug will increase from one (8 mg or placebo) tablet, to a maximum of 3 tablets over the first 6 weeks, guided by telephone monitoring of side effects and safety (2 and 4 weeks). Treatment will then continue for a further 6 weeks. Usual treatment (quetiapine) will be available to all participants if required, to ensure that distressing symptoms are not left untreated. Face to face assessments and blood sampling will be carried out after 6 and 12 weeks treatment, and over the telephone after treatment has completed (16 and 24 weeks). Recruitment will take place over 2 years in 15-20 NHS clinics, supported by local Research Networks and Parkinson’s UK. It will also be possible for participants to refer themselves to the study. Agreed recruitment targets are 5 participants per site in the first year, and progress will be assessed 9 months into recruitment by the Trial Management Group, to identify barriers to recruitment or retention to the study and ensure that they are addressed in a timely way. There will be focus group representation on biannual trial committees that will monitor progress towards recruitment targets, safety and
1. Aged over 55 years 2. Meet Brain Bank criteria for Parkinson’s disease 3. Visual hallucinations have been present at least weekly in the month before screening and are moderately severe 4. On a stable dose of anti-Parkinson’s medication, cholinesterase inhibitor or memantine for at least 28 days 5. Capacity to give informed consent or (if lacking) caregiver or other legal representative able to give consent 6. Pre-menopausal women, and men whose partners are of child bearing potential who agree to use effective contraception during the trial treatment period
1. Bradycardia (<50 bpm) (rescreen if reversible) 2. Congenital long QTc syndrome or presence of clinically significant prolongation of QTc (>460 ms for men or >470 ms for women) on ECG screening. 3. Severe hepatic failure (bilirubin >50 micromole/L) 4. Prescribed any antipsychotic medication in the past 2 weeks 5. Prescribed apomorphine 6. Prescribed tropisetron, granisetron, dolasetron 7. History of hypersensitivity to ondansetron and its excipients (or those of placebo) or drugs listed in 6 8. Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days