Trial of Ondansetron as a Parkinson's HAllucinations Treatment
- Conditions
- Dementia With Lewy BodiesParkinson's Hallucinations
- Interventions
- Registration Number
- NCT04167813
- Lead Sponsor
- University College, London
- Brief Summary
TOPHAT (Trial of Ondansetron as a Parkinson's HAllucinations Treatment) is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial of ondansetron (8-24mg/day) as a treatment for Parkinson's hallucinations, with a 12-week primary outcome and follow-up to 24 weeks.
- Detailed Description
This study investigates whether ondansetron, a drug used to treat post-operative sickness, has a meaningful treatment effect on Parkinson's hallucinations, and whether the drug is safe and cost effective for use in the NHS. We will compare ondansetron to placebo (a tablet that looks identical but contains no drug) over 12 weeks treatment, with follow up (once treatment ends) for a further 12 weeks. Assessments of symptoms will be carried out during treatment (after 6 and 12 weeks), and once treatment ends (18, 24 weeks), to measure hallucinations, delusions (false beliefs), Parkinson's symptoms (tremor, anxiety, sleep disturbance), memory, quality of life, possible side-effects such as constipation and headache, and the proportion of people who drop out due to side effects, or require additional treatment for their hallucinations. Blood drug concentration (measured after 6 and 12 weeks) will provide information on how quickly the drug is cleared from the body, and how this relates to treatment effects and side-effects, to guide future prescribing in people with Parkinson's. Based on knowledge of the average hallucinations scores in previous Parkinson's treatment studies, 306 people will be needed for the study to detect a meaningful treatment effect. The study will run for 4 years and involves a series of linked stages: (1) Trial set up across 20-30 UK centres; (2) Recruitment over 2 years; (3) Completion of follow up; and analysis, publication and dissemination of results.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 168
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Adults aged over 18 years.
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Meet MDS criteria for Parkinson's disease or revised criteria for DLB.
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Score of 3 or more on the SAPS-H visual hallucinations item, indicating the presence of visual hallucinations at least weekly in the previous month.
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Score of 3 or more on SAPS-H global rating, indicating moderate symptom severity.
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Score of 4 or more on CGI-S, indicating moderate symptom severity.
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On a stable dose of anti-Parkinson's medication, cholinesterase inhibitor or memantine for at least 28 days.
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Capacity to give informed consent or, if lacking, legal representative able to give consent.
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Pre-menopausal women, and men whose partners are of child bearing potential will agree to use effective contraception. 9) If treated with an antipsychotic drug at the time of enrolment, can still participate, provided the drug is stopped the day before trial medication is commenced.
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Bradycardia (<50 bpm) (rescreen if reversible).
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Congenital long QTc syndrome or presence of clinically significant prolongation of QTc (>460 ms for men or >470 ms for women) on ECG screening.
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Severe hepatic failure (bilirubin >50 micromole/L)
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Prescribed apomorphine (if apomorphine is discontinued, rescreen once stable on an alternative anti-Parkinson's treatment).
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Prescribed tropisetron, granisetron, dolasetron.
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History of hypersensitivity to ondansetron and its excipients (or those of placebo) or drugs listed in 5).
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Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Matched placebo Ondansetron 8mg or matched placebo tablets Participants randomised to the placebo treatment arm will take matched placebo, administered as tablets. Active Treatment Ondansetron 8mg or matched placebo tablets Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron.
- Primary Outcome Measures
Name Time Method Hallucinations 12 weeks Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
- Secondary Outcome Measures
Name Time Method Global illness severity 2, 4, 6, 12, 18, 24 weeks Clinical Global Impression of Severity Scale (1-7, higher scores indicate greater severity)
Safety and tolerability 2, 4, 6, 12, 18, 24 weeks Number of Participants With Treatment-Related Adverse Events
Hallucinations 6, 12 weeks University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)
Non-motor symptoms 2,4,6,12,18,24 weeks Non-motor symptoms scale (0-120, higher scores indicate greater severity
Delusions 2, 4, 6, 12, 18, 24 weeks Scale for Assessment of Positive Symptoms-Delusions (0-65 points, higher scores indicate greater symptom severity
Health related quality of life 6, 12, 18, 24 weeks EQ-5D-5L
Cost effectiveness 2, 4, 6, 12, 18, 24 weeks Health and social service utilisation
Pharmacokinetics, plasma concentrations of the study drug 6, 12 weeks Measured using a validated HPLC/MS assay
Feasibility and Acceptability of Video Consultation baseline, 6 and 12 weeks The feasibility of video consultation will be measured at baseline, 6 and 12 weeks by the proportion of participants who were able to successfully attend on at least one occasion, the proportion who successfully attended all three assessments, and a Satisfaction questionnaire that allows both quantitative and qualitative information to be collected.
Cognition 12 weeks Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)
Trial Locations
- Locations (23)
Dorset
🇬🇧Poole, United Kingdom
Salford
🇬🇧Salford, United Kingdom
Grampian
🇬🇧Aberdeen, United Kingdom
Betsi Cadwaladr
🇬🇧Bangor, United Kingdom
Pennine
🇬🇧Bury, United Kingdom
Addenbrookes
🇬🇧Cambridge, United Kingdom
Dartford
🇬🇧Dartford, United Kingdom
Tayside
🇬🇧Dundee, United Kingdom
Barking
🇬🇧London, United Kingdom
Glasgow
🇬🇧Glasgow, United Kingdom
Bart's Health
🇬🇧London, United Kingdom
Imperial College NHS
🇬🇧London, United Kingdom
Luton & Dunstable
🇬🇧London, United Kingdom
Northumbria
🇬🇧North Shields, United Kingdom
Cornwall
🇬🇧Redruth, United Kingdom
Sherwood Forest
🇬🇧Sutton In Ashfield, United Kingdom
Newcstle
🇬🇧Newcastle, United Kingdom
Lewisham
🇬🇧London, United Kingdom
UCLH NHS foundation trust
🇬🇧London, United Kingdom
Anuerin Bevan
🇬🇧Newport, United Kingdom
Oxford
🇬🇧Oxford, United Kingdom
North West Anglia
🇬🇧Peterborough, United Kingdom
North Midlands
🇬🇧Stoke, United Kingdom