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

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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

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.

Study Design

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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

MedlinePlus Genetics related topics: Parkinson disease

MedlinePlus related topics: Parkinson's Disease

Drug Information available for: Ondansetron hydrochloride Ondansetron

U.S. FDA Resources

Arms and Interventions

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).

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.

Drug: Ondansetron 8mg or matched placebo

Outcome Measures

Primary Outcome Measures :

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 :

To establish whether ondansetron will reduce delusions [ Time Frame: 2, 4, 6, 12, 18, 24 weeks ]
SAPS-D
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
To establish whether ondansetron improves quality of life in people with Parkinson's [ Time Frame: 6, 12, 18, 24 weeks ]
EQ-5D-5L
To investigate whether treatment effects will be associated with improved object recognition [ Time Frame: 6, 12 weeks ]
HVOT
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
To investigate pharmacokinetic variability and how this relates to clinical outcome [ Time Frame: 6, 12 weeks ]
Venous blood drug concentration

Eligibility Criteria

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.

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

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