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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 : Not yet recruiting
First Posted : November 19, 2019
Last Update Posted : November 19, 2019
Sponsor:
Collaborators:
MODEPHARMA Limited
PARKINSONS UK
PRIMENT
SEALED ENVELOPE
Wasdell Packaging Ltd
Custom Pharmaceuticals Limited
Information provided by (Responsible Party):
University College, London

Brief Summary:
TOPHAT 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 Drug: Ondansetron 8mg or matched placebo 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. We will also investigate whether treatment effects against hallucinations are related to improved processing of visual information. 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, 216 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 15-20 UK centres; (2) Recruitment over 2 years; (3) Completion of follow up; and analysis, publication and dissemination of results.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 216 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
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : April 1, 2022
Estimated Study Completion Date : April 1, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active Treatment

Participants randomised to the active treatment arm will take 8-24mg/day of ondansetron.

The dose will increase from a single daily 8mg tablet (AM) (weeks 1 and 2), to 16mg/day (8mg twice daily) (weeks 3 and 4), with a further increase to 24mg/day (8mg AM, 16mg PM) (weeks 5 and 6). Dose escalation will be guided by telephone safety monitoring prior to each dose increase, and a face to face assessment at the end of week 6.

Drug: Ondansetron 8mg or matched placebo
Participants will take 8-24mg/day of ondansetron or matched placebo. The dose will increase from a single daily 8mg tablet (AM) (weeks 1 and 2), to 16mg/day (8mg twice daily) (weeks 3 and 4), with a further increase to 24mg/day (8mg AM, 16mg PM) (weeks 5 and 6).

Placebo Comparator: Matched placebo

Participants randomised to the placebo treatment arm will take 8-24mg/day of matched placebo.

The dose will increase from a single daily 8mg tablet (AM) (weeks 1 and 2), to 16mg/day (8mg twice daily) (weeks 3 and 4), with a further increase to 24mg/day (8mg AM, 16mg PM) (weeks 5 and 6). Dose escalation will be guided by telephone safety monitoring prior to each dose increase, and a face to face assessment at the end of week 6.

Drug: Ondansetron 8mg or matched placebo
Participants will take 8-24mg/day of ondansetron or matched placebo. The dose will increase from a single daily 8mg tablet (AM) (weeks 1 and 2), to 16mg/day (8mg twice daily) (weeks 3 and 4), with a further increase to 24mg/day (8mg AM, 16mg PM) (weeks 5 and 6).




Primary Outcome Measures :
  1. Visual hallucinations [ Time Frame: SAPS (H) at 12 weeks ]
    Measured using the Scale for Assessment of Positive Symptoms (SAPS) Hallucinations (H) scores


Secondary Outcome Measures :
  1. To establish whether ondansetron will reduce delusions [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]
    SAPS-D

  2. To determine safety and tolerability of ondansetron in people with Parkinson's [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]
    Adverse event checklist administered

  3. To establish whether ondansetron improves quality of life in people with Parkinson's [ Time Frame: 6, 12, 18, 24 weeks ]
    EQ-5D-5L

  4. To investigate whether treatment effects will be associated with improved object recognition [ Time Frame: 6, 12 weeks ]
    HVOT

  5. To determine whether ondansetron is cost effective for NHS use [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]
    Concomitant medication log, rescue quetiapine medication, and estimated resource use from adverse event checklist informatio

  6. To investigate pharmacokinetic variability and how this relates to clinical outcome [ Time Frame: 6, 12 weeks ]
    Venous blood drug concentration



Information from the National Library of Medicine

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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. 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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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
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United Kingdom
UCLH NHS foundation trust
London, United Kingdom
Contact: Olga Zubko       o.zubko@ucl.ac.uk   
Contact: Suzanne Reeves       suzanne.reeves@ucl.ac.uk   
Sponsors and Collaborators
University College, London
MODEPHARMA Limited
PARKINSONS UK
PRIMENT
SEALED ENVELOPE
Wasdell Packaging Ltd
Custom Pharmaceuticals Limited
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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: November 19, 2019
Last Verified: November 2019
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
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Synucleinopathies
Neurodegenerative Diseases
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
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Anti-Anxiety Agents