Trial of Ondansetron as a Parkinson's HAllucinations Treatment (TOP HAT)
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ClinicalTrials.gov Identifier: NCT04167813 |
Recruitment Status :
Recruiting
First Posted : November 19, 2019
Last Update Posted : April 29, 2022
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Condition or disease | Intervention/treatment | Phase |
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Parkinson's Hallucinations Dementia With Lewy Bodies | Drug: Ondansetron 8mg or matched placebo tablets | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 306 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Intervention Model Description: | TOPHAT is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial |
Masking: | Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) |
Masking Description: | Double-blind |
Primary Purpose: | Treatment |
Official Title: | Trial of Ondansetron as a Parkinson's HAllucinations Treatment |
Actual Study Start Date : | October 1, 2021 |
Estimated Primary Completion Date : | January 1, 2024 |
Estimated Study Completion Date : | January 14, 2025 |

Arm | Intervention/treatment |
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Active Comparator: Active Treatment
Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron.
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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 Other Name: Tablet, film coated |
Placebo Comparator: Matched placebo
Participants randomised to the placebo treatment arm will take matched placebo, administered as tablets.
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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 Other Name: Tablet, film coated |
- Hallucinations [ Time Frame: 12 weeks ]Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
- Delusions [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]Scale for Assessment of Positive Symptoms-Delusions (0-65 points, higher scores indicate greater symptom severity
- Safety and tolerability [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]Number of Participants With Treatment-Related Adverse Events
- Health related quality of life [ Time Frame: 6, 12, 18, 24 weeks ]EQ-5D-5L
- Cost effectiveness [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]Health and social service utilisation
- Pharmacokinetics, plasma concentrations of the study drug [ Time Frame: 6, 12 weeks ]Measured using a validated HPLC/MS assay
- Hallucinations [ Time Frame: 2, 4, 6, 18, 24 weeks ]Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
- Global illness severity [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]Clinical Global Impression of Severity Scale (1-7, higher scores indicate greater severity)
- Non-motor symptoms [ Time Frame: 2,4,6,12,18,24 weeks ]Non-motor symptoms scale (0-120, higher scores indicate greater severity
- Cognition [ Time Frame: 12 weeks ]Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)
- Hallucinations [ Time Frame: 6, 12 weeks ]University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)
- Feasibility and Acceptability of Video Consultation [ Time Frame: 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.

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adults aged over 18 years.
- Meet MDS criteria for Parkinson's disease or revised criteria for DLB.
- 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.
- Score of 3 or more on SAPS-H global rating, indicating moderate symptom severity.
- Score of 4 or more on CGI-S, indicating moderate symptom severity.
- On a stable dose of anti-Parkinson's medication, cholinesterase inhibitor or memantine for at least 28 days.
- 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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Exclusion Criteria:
- Bradycardia (<50 bpm) (rescreen if reversible).
- Congenital long QTc syndrome or presence of clinically significant prolongation of QTc (>460 ms for men or >470 ms for women) on ECG screening.
- Severe hepatic failure (bilirubin >50 micromole/L)
- Prescribed apomorphine (if apomorphine is discontinued, rescreen once stable on an alternative anti-Parkinson's treatment).
- Prescribed tropisetron, granisetron, dolasetron.
- 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.
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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04167813
Contact: Olga Zubko, PhD | 020 76759073 | o.zubko@ucl.ac.uk | |
Contact: Suzanne Reeves | suzanne.reeves@ucl.ac.uk |

Responsible Party: | University College, London |
ClinicalTrials.gov Identifier: | NCT04167813 |
Other Study ID Numbers: |
17/0909 |
First Posted: | November 19, 2019 Key Record Dates |
Last Update Posted: | April 29, 2022 |
Last Verified: | April 2022 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | No |
Studies a U.S. FDA-regulated Device Product: | No |
Parkinson Disease Hallucinations Lewy Body Disease Parkinsonian Disorders Basal Ganglia Diseases Brain Diseases Central Nervous System Diseases Nervous System Diseases Movement Disorders Synucleinopathies Neurodegenerative Diseases Dementia Neurocognitive Disorders Mental Disorders Perceptual Disorders |
Neurobehavioral Manifestations Neurologic Manifestations Ondansetron Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Gastrointestinal Agents Antipruritics Dermatologic Agents Serotonin Antagonists Serotonin Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Antipsychotic Agents |