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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
Sponsor:
Collaborators:
MODEPHARMA Limited
PARKINSONS UK
PRIMENT
SEALED ENVELOPE
Wasdell Packaging Ltd
Custom Pharmaceuticals Limited
Information provided by (Responsible Party):
University College, London

Study Description
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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.

Condition or disease Intervention/treatment Phase
Parkinson's Hallucinations Dementia With Lewy Bodies Drug: Ondansetron 8mg or matched placebo tablets Phase 2

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
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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

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Active Comparator: Active Treatment
Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron.
 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.
 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


Outcome Measures
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Primary Outcome Measures :
  1. Hallucinations [ Time Frame: 12 weeks ]
    Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations


Secondary Outcome Measures :
  1. 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

  2. Safety and tolerability [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]
    Number of Participants With Treatment-Related Adverse Events

  3. Health related quality of life [ Time Frame: 6, 12, 18, 24 weeks ]
    EQ-5D-5L

  4. Cost effectiveness [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]
    Health and social service utilisation

  5. Pharmacokinetics, plasma concentrations of the study drug [ Time Frame: 6, 12 weeks ]
    Measured using a validated HPLC/MS assay

  6. 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

  7. 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)

  8. Non-motor symptoms [ Time Frame: 2,4,6,12,18,24 weeks ]
    Non-motor symptoms scale (0-120, higher scores indicate greater severity

  9. Cognition [ Time Frame: 12 weeks ]
    Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)

  10. Hallucinations [ Time Frame: 6, 12 weeks ]
    University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)

  11. 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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

    -

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.

    -

Contacts and Locations
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Information from the National Library of Medicine

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


Contacts
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Contact: Olga Zubko, PhD 020 76759073 o.zubko@ucl.ac.uk
Contact: Suzanne Reeves suzanne.reeves@ucl.ac.uk

Locations
Show Show 23 study locations
Sponsors and Collaborators
University College, London
MODEPHARMA Limited
PARKINSONS UK
PRIMENT
SEALED ENVELOPE
Wasdell Packaging Ltd
Custom Pharmaceuticals Limited
More Information
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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

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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