Clinical trial NCT04167813: Trial of Ondansetron as a Parkinson's HAllucinations Treatment
Official title: Trial of Ondansetron as a Parkinson's HAllucinations Treatment
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Parkinson's Hallucinations
Dementia With Lewy Bodies
Lead sponsor: University College, London
Sponsor class: OTHER
Collaborators: name: MODEPHARMA Limited
name: Parkinson's UK
name: PRIMENT
name: SEALED ENVELOPE
name: Wasdell Packaging Ltd
name: Custom Pharmaceuticals Limited
First posted: 2019-11-19
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: TOPHAT is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Adults aged over 18 years.
2. Meet MDS criteria for Parkinson's disease or revised criteria for DLB.
3. 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.
4. Score of 3 or more on SAPS-H global rating, indicating moderate symptom severity.
5. Score of 4 or more on CGI-S, indicating moderate symptom severity.
6. On a stable dose of anti-Parkinson's medication, cholinesterase inhibitor or memantine for at least 28 days.
7. Capacity to give informed consent or, if lacking, legal representative able to give consent.
8. 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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Exclusion Criteria:

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 apomorphine (if apomorphine is discontinued, rescreen once stable on an alternative anti-Parkinson's treatment).
5. Prescribed tropisetron, granisetron, dolasetron.
6. History of hypersensitivity to ondansetron and its excipients (or those of placebo) or drugs listed in 5).
7. Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days.

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Primary outcomes:
measure: Hallucinations
timeFrame: 12 weeks
Secondary outcomes:
measure: Delusions
timeFrame: 2, 4, 6, 12, 18, 24 weeks
measure: Safety and tolerability
timeFrame: 2, 4, 6, 12, 18, 24 weeks
measure: Health related quality of life
timeFrame: 6, 12, 18, 24 weeks
measure: Cost effectiveness
timeFrame: 2, 4, 6, 12, 18, 24 weeks
measure: Pharmacokinetics, plasma concentrations of the study drug
timeFrame: 6, 12 weeks
measure: Hallucinations
timeFrame: 2, 4, 6, 18, 24 weeks
measure: Global illness severity
timeFrame: 2, 4, 6, 12, 18, 24 weeks
measure: Non-motor symptoms
timeFrame: 2,4,6,12,18,24 weeks
measure: Cognition
timeFrame: 12 weeks
measure: Hallucinations
timeFrame: 6, 12 weeks
measure: Feasibility and Acceptability of Video Consultation
timeFrame: baseline, 6 and 12 weeks
Other outcomes:
Locations:
city: Aberdeen
country: United Kingdom
facility: Grampian
city: Bangor
country: United Kingdom
facility: Betsi Cadwaladr
city: Bury
country: United Kingdom
facility: Pennine
city: Cambridge
country: United Kingdom
facility: Addenbrookes
city: Dartford
country: United Kingdom
facility: Dartford
city: Dundee
country: United Kingdom
facility: Tayside
city: Glasgow
country: United Kingdom
facility: Glasgow
city: London
country: United Kingdom
facility: Barking
city: London
country: United Kingdom
facility: Bart's Health
city: London
country: United Kingdom
facility: Imperial College NHS
city: London
country: United Kingdom
facility: Lewisham
city: London
country: United Kingdom
facility: Luton & Dunstable
city: London
country: United Kingdom
facility: UCLH NHS foundation trust
city: Newcastle
country: United Kingdom
facility: Newcstle
city: Newport
country: United Kingdom
facility: Anuerin Bevan
city: North Shields
country: United Kingdom
facility: Northumbria
city: Oxford
country: United Kingdom
facility: Oxford
city: Peterborough
country: United Kingdom
facility: North West Anglia
city: Poole
country: United Kingdom
facility: Dorset
city: Redruth
country: United Kingdom
facility: Cornwall
city: Salford
country: United Kingdom
facility: Salford
city: Stoke
country: United Kingdom
facility: North Midlands
city: Sutton In Ashfield
country: United Kingdom
facility: Sherwood Forest
Study officials:
References: