Parkinson's HallucinationsPhase 2TOP HATNCT04167813
Trial of Ondansetron as a Parkinson's HAllucinations Treatment
A Phase 2 study of Parkinson's Hallucinations and Dementia With Lewy Bodies, run by University College, London at 23 sites in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson's Hallucinations, Dementia With Lewy Bodies
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 168 participants
- Where
- 23 sitesUnited Kingdom
- Study dates
- 1 Oct 2021to 30 Aug 2024
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 9Show fewer
- Capacity to give informed consent or, if lacking, legal representative able to give consent.
- 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.
- -
Who cannot join
- 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).
- Participation in another Clinical Trial of an Investigational Medicinal Product (IMP) in the previous 28 days.
- -
Trial locations and contacts
23 sites in 1 country.
23 sites in 1 country
United Kingdom23 sites
Grampian
Aberdeen
Betsi Cadwaladr
Bangor
Pennine
Bury
Addenbrookes
Cambridge
Dartford
Dartford
Tayside
Dundee
Glasgow
Glasgow
Barking
London
Bart's Health
London
Imperial College NHS
London
Lewisham
London
Luton & Dunstable
London
UCLH NHS foundation trust
London
Newcstle
Newcastle
Anuerin Bevan
Newport
Northumbria
North Shields
Oxford
Oxford
North West Anglia
Peterborough
Dorset
Poole
Cornwall
Redruth
Salford
Salford
North Midlands
Stoke
Sherwood Forest
Sutton in Ashfield
About this study
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.
Read the 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.
- Being tested
- Ondansetron 8mg or matched placebo tablets
- Medical subject headings
- Lewy Body Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ondansetron 8mg or matched placebo tabletsDrug
Also called Tablet, film coated
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
| Study group | Role | What they receive |
|---|---|---|
| Active Treatment | Active comparator | Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron. Receives: Drug: Ondansetron 8mg or matched placebo tablets |
| Matched placebo | Placebo comparator | Participants randomised to the placebo treatment arm will take matched placebo, administered as tablets. Receives: Drug: Ondansetron 8mg or matched placebo tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hallucinations
Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
Measured: 12 weeks
Secondary outcomes (11)
Delusions
Scale for Assessment of Positive Symptoms-Delusions (0-65 points, higher scores indicate greater symptom severity
Measured: 2, 4, 6, 12, 18, 24 weeks
Safety and tolerability
Number of Participants With Treatment-Related Adverse Events
Measured: 2, 4, 6, 12, 18, 24 weeks
Health related quality of life
EQ-5D-5L
Measured: 6, 12, 18, 24 weeks
Cost effectiveness
Health and social service utilisation
Measured: 2, 4, 6, 12, 18, 24 weeks
Pharmacokinetics, plasma concentrations of the study drug
Measured using a validated HPLC/MS assay
Measured: 6, 12 weeks
Hallucinations
Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
Measured: 2, 4, 6, 18, 24 weeks
Global illness severity
Clinical Global Impression of Severity Scale (1-7, higher scores indicate greater severity)
Measured: 2, 4, 6, 12, 18, 24 weeks
Non-motor symptoms
Non-motor symptoms scale (0-120, higher scores indicate greater severity
Measured: 2,4,6,12,18,24 weeks
Cognition
Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)
Measured: 12 weeks
Hallucinations
University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)
Measured: 6, 12 weeks
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.
Measured: baseline, 6 and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2019
- Study start1 Oct 2021
- Primary completion30 Aug 2024 (estimated)
- Study completion30 Aug 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Parkinson's HallucinationsStudies of the same condition, open and under way.
- More trials run by University College, LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- TOPHAT is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 168 participants (actual)
Sponsor and investigators
- Lead sponsor
- University College, London
- Sponsor type
- University, hospital or other
- Collaborators
- MODEPHARMA Limited, Parkinson's UK, PRIMENT, SEALED ENVELOPE, Wasdell Packaging Ltd, Custom Pharmaceuticals Limited
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04167813
- Sponsor's protocol ID
- 17/0909
- Acronym
- TOP HAT
- Status last verified
- Mar 2024
- First submitted
- 15 Nov 2019
- Last updated
- 27 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Ondansetron as a Parkinson's HAllucinations Treatment
- ClinicalTrials.gov ID
- NCT04167813
- Acronym / sponsor ID
- TOP HAT / 17/0909
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 168 participants (actual)
- Lead sponsor
- University College, LondonUniversity, hospital or other
- Collaborators
- MODEPHARMA Limited, Parkinson's UK, PRIMENT, SEALED ENVELOPE, Wasdell Packaging Ltd, Custom Pharmaceuticals Limited
- Study start
- 1 Oct 2021 (actual)
- Primary completion
- 30 Aug 2024 (estimated)
- Study completion
- 30 Aug 2024 (estimated)
- First posted
- 19 Nov 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- TOPHAT is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial
| Arm | Type | Receives |
|---|---|---|
| Active Treatment | Active comparator | Drug: Ondansetron 8mg or matched placebo tabletsParticipants randomised to the active treatment arm will take 8-24mg/day of ondansetron. |
| Matched placebo | Placebo comparator | Drug: Ondansetron 8mg or matched placebo tabletsParticipants randomised to the placebo treatment arm will take matched placebo, administered as tablets. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ondansetron 8mg or matched placebo tabletsAlso: Tablet, film coatedParticipants 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 | Drug | Active Treatment, Matched placebo |
Primary outcome
Hallucinations
Time frame: 12 weeks
Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
11 secondary outcomes
Delusions
Time frame: 2, 4, 6, 12, 18, 24 weeks
Safety and tolerability
Time frame: 2, 4, 6, 12, 18, 24 weeks
Health related quality of life
Time frame: 6, 12, 18, 24 weeks
Cost effectiveness
Time frame: 2, 4, 6, 12, 18, 24 weeks
Pharmacokinetics, plasma concentrations of the study drug
Time frame: 6, 12 weeks
Hallucinations
Time frame: 2, 4, 6, 18, 24 weeks
Global illness severity
Time frame: 2, 4, 6, 12, 18, 24 weeks
Non-motor symptoms
Time frame: 2,4,6,12,18,24 weeks
Cognition
Time frame: 12 weeks
Hallucinations
Time frame: 6, 12 weeks
Feasibility and Acceptability of Video Consultation
Time frame: baseline, 6 and 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
23 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study of Parkinson's Hallucinations and Dementia With Lewy Bodies, run by University College, London at 23 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hallucinations (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024.