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Trial of Ondansetron as a Parkinson's HAllucinations Treatment (TOP HAT)

Primary Purpose

Parkinson's Hallucinations, Dementia With Lewy Bodies

Status
Recruiting
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Ondansetron 8mg or matched placebo tablets
Sponsored by
University College, London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson's Hallucinations

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

    -

Sites / Locations

  • GrampianRecruiting
  • Betsi CadwaladrRecruiting
  • PennineRecruiting
  • AddenbrookesRecruiting
  • DartfordRecruiting
  • TaysideRecruiting
  • GlasgowRecruiting
  • BarkingRecruiting
  • Bart's HealthRecruiting
  • Imperial College NHSRecruiting
  • LewishamRecruiting
  • Luton & DunstableRecruiting
  • UCLH NHS foundation trustRecruiting
  • NewcstleRecruiting
  • Anuerin BevanRecruiting
  • NorthumbriaRecruiting
  • OxfordRecruiting
  • North West AngliaRecruiting
  • DorsetRecruiting
  • CornwallRecruiting
  • SalfordRecruiting
  • North MidlandsRecruiting
  • Sherwood ForestRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Active Treatment

Matched placebo

Arm Description

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

Participants randomised to the placebo treatment arm will take matched placebo, administered as tablets.

Outcomes

Primary Outcome Measures

Hallucinations
Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations

Secondary Outcome Measures

Delusions
Scale for Assessment of Positive Symptoms-Delusions (0-65 points, higher scores indicate greater symptom severity
Safety and tolerability
Number of Participants With Treatment-Related Adverse Events
Health related quality of life
EQ-5D-5L
Cost effectiveness
Health and social service utilisation
Pharmacokinetics, plasma concentrations of the study drug
Measured using a validated HPLC/MS assay
Hallucinations
Scale for Assessment of Positive Symptoms-Hallucinations (0-35 points, higher scores indicate greater severity of hallucinations
Global illness severity
Clinical Global Impression of Severity Scale (1-7, higher scores indicate greater severity)
Non-motor symptoms
Non-motor symptoms scale (0-120, higher scores indicate greater severity
Cognition
Standardised Mini-Mental State Examination (0-30, higher scores indicate better performance)
Hallucinations
University of Miami Parkinson's disease Hallucinations Questionnaire (0-15, where higher scores indicate greater symptom severity)
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.

Full Information

First Posted
November 15, 2019
Last Updated
April 22, 2022
Sponsor
University College, London
Collaborators
MODEPHARMA Limited, PARKINSONS UK, PRIMENT, SEALED ENVELOPE, Wasdell Packaging Ltd, Custom Pharmaceuticals Limited
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1. Study Identification

Unique Protocol Identification Number
NCT04167813
Brief Title
Trial of Ondansetron as a Parkinson's HAllucinations Treatment
Acronym
TOP HAT
Official Title
Trial of Ondansetron as a Parkinson's HAllucinations Treatment
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Recruiting
Study Start Date
October 1, 2021 (Actual)
Primary Completion Date
January 1, 2024 (Anticipated)
Study Completion Date
January 14, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University College, London
Collaborators
MODEPHARMA Limited, PARKINSONS UK, PRIMENT, SEALED ENVELOPE, Wasdell Packaging Ltd, Custom Pharmaceuticals Limited

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson's Hallucinations, Dementia With Lewy Bodies

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
TOPHAT is a double blind, individually randomized, placebo-controlled, parallel group, flexible dose trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind
Allocation
Randomized
Enrollment
306 (Anticipated)

8. Arms, Groups, and Interventions

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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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. 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: 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. -
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Olga Zubko, PhD
Phone
020 76759073
Email
o.zubko@ucl.ac.uk
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne Reeves
Email
suzanne.reeves@ucl.ac.uk
Facility Information:
Facility Name
Grampian
City
Aberdeen
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Betsi Cadwaladr
City
Bangor
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Pennine
City
Bury
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Addenbrookes
City
Cambridge
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Dartford
City
Dartford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Tayside
City
Dundee
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Glasgow
City
Glasgow
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Barking
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Bart's Health
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Imperial College NHS
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Lewisham
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Luton & Dunstable
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
UCLH NHS foundation trust
City
London
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olga Zubko
Email
o.zubko@ucl.ac.uk
First Name & Middle Initial & Last Name & Degree
Suzanne Reeves
Email
suzanne.reeves@ucl.ac.uk
Facility Name
Newcstle
City
Newcastle
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Anuerin Bevan
City
Newport
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Northumbria
City
North Shields
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Oxford
City
Oxford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
North West Anglia
City
Peterborough
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Dorset
City
Poole
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Cornwall
City
Redruth
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Salford
City
Salford
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
North Midlands
City
Stoke
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Sherwood Forest
City
Sutton In Ashfield
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

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Trial of Ondansetron as a Parkinson's HAllucinations Treatment

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