Trial of Ondansetron as a Parkinson's HAllucinations Treatment

Dementia With Lewy Bodies Clinical Trial

— TOP HAT  

Official title:

Trial of Ondansetron as a Parkinson's HAllucinations Treatment

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04167813
• Other study ID #: 17/0909
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: October 1, 2021
• Est. completion date: August 30, 2024

Study information

• Verified date: March 2024
• Source: University College, London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 168
• Est. completion date: August 30, 2024
• Est. primary completion date: August 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. -

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. -

Related Conditions & MeSH terms

• Dementia With Lewy Bodies
• Hallucinations
• Lewy Body Disease
• Parkinson Disease
• Parkinson's Hallucinations

Intervention

Drug:
• Ondansetron 8mg or matched placebo tablets
Participants will take one tablet daily in weeks 1 and 2, two tablets daily in weeks 3 and 4 and 3 tablets daily in weeks 5 and 6. Dose escalation will be guided by tolerability, through telephone safety monitoring prior to each dose increase

Locations

Country	Name	City	State
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	Glasgow	Glasgow
United Kingdom	Barking	London
United Kingdom	Bart's Health	London
United Kingdom	Imperial College NHS	London
United Kingdom	Lewisham	London
United Kingdom	Luton & Dunstable	London
United Kingdom	UCLH NHS foundation trust	London
United Kingdom	Newcstle	Newcastle
United Kingdom	Anuerin Bevan	Newport
United Kingdom	Northumbria	North Shields
United Kingdom	Oxford	Oxford
United Kingdom	North West Anglia	Peterborough
United Kingdom	Dorset	Poole
United Kingdom	Cornwall	Redruth
United Kingdom	Salford	Salford
United Kingdom	North Midlands	Stoke
United Kingdom	Sherwood Forest	Sutton In Ashfield

Sponsors (7)

Lead Sponsor	Collaborator
University College, London	Custom Pharmaceuticals Limited, MODEPHARMA Limited, PARKINSONS UK, PRIMENT, SEALED ENVELOPE, Wasdell Packaging Ltd

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hallucinations	Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations	12 weeks
Secondary	Delusions	Scale for Assessment of Positive Symptoms-Delusions (0-65 points, higher scores indicate greater symptom severity	2, 4, 6, 12, 18, 24 weeks
Secondary	Safety and tolerability	Number of Participants With Treatment-Related Adverse Events	2, 4, 6, 12, 18, 24 weeks
Secondary	Health related quality of life	EQ-5D-5L	6, 12, 18, 24 weeks
Secondary	Cost effectiveness	Health and social service utilisation	2, 4, 6, 12, 18, 24 weeks
Secondary	Pharmacokinetics, plasma concentrations of the study drug	Measured using a validated HPLC/MS assay	6, 12 weeks
Secondary	Hallucinations	Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations	2, 4, 6, 18, 24 weeks
Secondary	Global illness severity	Clinical Global Impression of Severity Scale (1-7, higher scores indicate greater severity)	2, 4, 6, 12, 18, 24 weeks
Secondary	Non-motor symptoms	Non-motor symptoms scale (0-120, higher scores indicate greater severity	2,4,6,12,18,24 weeks
Secondary	Cognition	Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)	12 weeks
Secondary	Hallucinations	University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)	6, 12 weeks
Secondary	Feasibility and Acceptability of Video Consultation	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.	baseline, 6 and 12 weeks