Condition category
Nervous System Diseases
Date applied
08/04/2019
Date assigned
16/04/2019
Last edited
20/04/2020
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Suspended

Plain English Summary

Background and study aims
Parkinson’s disease is a common condition particularly affecting older people. Falls are a very frequent complication of the disease affecting 60% of people with Parkinson's every year. As the population ages, the number of people living with Parkinson’s disease and the occurrence of complications will increase. The loss of the chemical dopamine in the brain causes walking in Parkinson's to become slower, unsteady and irregular. People with the condition are therefore at a very high risk of falling. To some extent, people can compensate for these changes by paying more attention to their walking. However, Parkinson's also diminishes memory and thinking ability. This decreases people’s ability to pay attention to their walking, especially when doing something at the same time.

Who can participate?
Cholinesterase inhibitor (ChEis) are drugs that are currently used to treat people with memory problems in Parkinson’s. The effect of these drugs on falls in Parkinson’s has been tested to show that treatment has the potential to almost halve the number of falls.
This trial aims to definitively determine whether cholinesterase inhibitors (ChEi), can prevent falls in Parkinson’s and whether this treatment is cost-effective.

What does the study involve?
600 participants with Parkinson’s disease will be enrolled from hospitals throughout the UK. Participants will be randomly assigned to either receive the drug (ChEi) via a patch or receive a placebo (dummy) treatment via a patch. Neither the researchers nor the participants will know which group they are in. Participants will take the medication for 12 months and record any falls that they experience in diaries.

What are the possible benefits and risks of participating?
There are a few possible benefits of taking part in this trial. If allocated to the group that receives the active medication, walking unsteadiness and/or balance may improve and falls may be less likely, but there is no guarantee. The information we get from this study will improve the treatment of people with Parkinson’s disease in the future.
There are also some risks and discomforts of the trial. The assessments are quite detailed and therefore may cause tiredness and fatigue.
Like all medicines, the treatment can cause side effects, although not everybody gets them. Because the medication is already used to treat memory problems we know a lot about the side effects.
Side effects are experienced more frequently when you start your medicine or increase the dose. In most cases, side effects will gradually disappear.

Where is the study run from?
Bristol Medical School, University of Bristol, UK

When is the study starting and how long is it expected to run for?
September 2019 to September 2022

Who is funding the study?
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC)

Who is the main contact?
Dr. Sandra Neumann, Chief-pd@bristol.ac.uk

Trial website

http://www.bristol.ac.uk/chief-pd

Contact information

Type

Scientific

Primary contact

Dr Sandra Neumann

ORCID ID

http://orcid.org/0000-0002-7306-9047

Contact details

Population Health Sciences
Bristol Medical School
University of Bristol
G11
1-5 Whiteladies Road
Bristol
BS8 1NU
United Kingdom
01174283111
Chief-pd@bristol.ac.uk

Additional identifiers

EudraCT number

2018-003219-23

ClinicalTrials.gov number

Nil known

Protocol/serial number

40906

Study information

Scientific title

CHIEF-PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson’s Disease): A phase 3 randomised double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson’s disease

Acronym

CHIEF-PD

Study hypothesis

Cholinesterase inhibitor (ChEi) treatment prevents people with Parkinson's from falling and is cost-effective.

Ethics approval

Approved 17/05/2019, Southwest Central Bristol Research Ethics Committee (Health Research Authority, Whitefriars, Level 3 Block B, Lewins Mead, Bristol, BS1 2NT; 02071048046; nrescommittee.southwest-bristol@nhs.net) ref: 19/SW/0043

Study design

Randomised; Interventional; Design type: Treatment, Drug

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Parkinson's Disease

Intervention

Current interventions as of 05/12/2019:
Previous interventions:
600 participants with Parkinson’s disease will be enrolled from hospitals throughout the UK. Participants will be randomly assigned to either receive the drug (ChEi) via a patch or receive a placebo (dummy) treatment via a patch. Participants are allocated to the two treatment arms using a technique that minimises the differences between the groups but still allocated people randomly. Neither the researchers nor the participants will know which group they are in. Participants will take the medication for 12 months and record any falls that they experience in diaries and through monthly telephone calls.

TRIAL ASSESSMENTS OVERVIEW
At baseline (enrolment) and follow-up (12 months) detailed tests of Parkinson's disease are undertaken to determine what effect the treatment has on the motor and non-motor symptoms of the condition. At monthly intervals between visits participants will complete a diary (detailed below).

BASELINE VISIT (2.5 hours)
Eligibility confirmation (10 minutes)
Consent (15 minutes)
Disease and functional measures (approx 1.5 hours)
1. Questionnaires (optionally can be completed pre-visit) (15 minutes):
1.1 Freezing of gait (New Freezing of Gait questionnaire NFOG-Q)
1.2 Fear of falling (Iconographical Falls Efficacy Scale [ICON-FES])
1.3 Mood (Geriatric Depression Scale [GDS])
1.4 Capability of older people (ICEpop CAPability measure for Older people [ICECAP-O])
1.5 Quality of life (EQ-5D-5L)
1.6 Starkstein Apathy Scale (SAS)
1.7 Swallowing (Swallowing Disturbance Questionnaire [SDQ])

2. Sociodemographics, medical and drug history
3. Brief examination: heart rate (+/- electrocardiogram if indicated), blood pressure, height and weight, Movement Disorder Society Unified Parkinson's Disease Scale (MDS-UPDRS) parts 3 and 4, frailty and gait assessment, Short Physical Performance Battery (SPPB).
4. Functional measures:
4.1 Cognition (Montreal Cognitive Assessment [MoCA])

SELF COMPLETION OF MONTHLY DIARY and PHONE CALLS
Falls are recorded in a patient diary which is posted back to the central team on a monthly basis. Participants are telephoned to remind them about the diaries, to identify any side effects that have occurred.
Questionnaire assessments of quality of life and healthcare use are completed in the diary at months 1, 3, 6, 9 and 12 in order to determine whether the treatment, if successful, is also cost-effective.

_____
Previous interventions:
600 participants with Parkinson’s disease will be enrolled from hospitals throughout the UK. Participants will be randomly assigned to either receive the drug (ChEi) via a patch or receive a placebo (dummy) treatment via a patch. Participants are allocated to the two treatment arms using a technique that minimises the differences between the groups but still allocated people randomly. Neither the researchers nor the participants will know which group they are in. Participants will take the medication for 12 months and record any falls that they experience in diaries and through monthly telephone calls.

TRIAL ASSESSMENTS OVERVIEW
At baseline (enrolment) and follow-up (12 months) detailed tests of Parkinson's disease are undertaken to determine what effect the treatment has on the motor and non-motor symptoms of the condition. At monthly intervals between visits participants will complete a diary (detailed below).

BASELINE VISIT (2.5 hours)
Eligibility confirmation (10 minutes)
Consent (15 minutes)
Disease and functional measures (approx 1.5 hours)
1. Questionnaires (optionally can be completed pre-visit) (15 minutes):
1.1 Freezing of gait (New Freezing of Gait questionnaire NFOG-Q)
1.2 Fear of falling (Iconographical Falls Efficacy Scale [ICON-FES])
1.3 Mood (Geriatric Depression Scale [GDS])
1.4 Capability of older people (ICEpop CAPability measure for Older people [ICECAP-O])
1.5 Quality of life (EQ-5D-5L)
2. Sociodemographics, medical and drug history
3. Brief examination: heart rate (+/- electrocardiogram if indicated), blood pressure, height and weight, Movement Disorder Society Unified Parkinson's Disease Scale (MDS-UPDRS) parts 3 and 4, frailty and gait assessment, Short Physical Performance Battery (SPPB).
4. Functional measures:
4.1 Cognition (Montreal Cognitive Assessment [MoCA])
4.2 Swallowing (Swallowing Disturbance Questionnaire [SDQ])

SELF COMPLETION OF MONTHLY DIARY and PHONE CALLS
Falls are recorded in a patient diary which is posted back to the central team on a monthly basis. Participants are telephoned to remind them about the diaries, to identify any side effects that have occurred.
Questionnaire assessments of quality of life and healthcare use are completed in the diary at months 1, 3, 6, 9 and 12 in order to determine whether the treatment, if successful, is also cost-effective.

Intervention type

Drug

Phase

Phase III

Drug names

Rivastigmine

Primary outcome measure

Fall rate measured using monthly diaries and telephone calls prospectively over 12 months from the day the IMP is commenced. A fall is defined as “unintentionally coming to rest on the ground or other lower surface without overwhelming external force or a major internal event”

Secondary outcome measures

Current secondary outcome measures as of 05/12/2019:
1. Parkinson's Disease markers assessed via the MDS-UPDRS total score in the practically defined ON state and each individual subscale (1-4) measured at baseline and 12months
2. Freezing of gait assessed via the New Freezing Of Gait Questionnaire (NFOGQ) measured at baseline and 12months
3. Frailty and physical performance assessed via Short Physical Performance Battery (SPPB), gait speed and frailty status measured at baseline and 12months
4. Cognition assessed via Montreal Cognitive Assessment (MoCA) measured at baseline and 12months
5. Depression assessed via Geriatric Depression Scale (GDS) measured at baseline and 12months
6. Apathy assessed via the Starkstein Apathy Scale (SAS)
7. Fear of falling assessed via the Iconographical Fall Efficacy Scale (ICON-FES) measured at baseline and 12months
8. Dysphagia assessed via the Swallowing Disturbance Questionnaire (SDQ) measured at baseline and 12months
9. Participant health-related quality of life assessed via the EuroQoL 5D-5L health status questionnaire (EQ-5D-5L) measured at baseline, 1 month, 3 months, 6 months, 9 months and 12months
10.Capability of older people assessed via the ICEpop CAPability measure for Older people (ICECAP-O) measured at baseline and 12 months
11. Mortality (all cause and PD related) through Office of National Statistics measured at 12months
12. Cost-effectiveness and NHS resource use through EQ-5D-5L and NHS Episode Statistics (HES) data
Secondary outcome via CHIEF-PD carer study:
12. Care-related quality of life via the Carer Experience Scale (CES) measured at baseline and 12months
_____
Previous secondary outcome measures:
1. Parkinson's Disease markers assessed via the MDS-UPDRS total score in the practically defined ON state and each individual subscale (1-4) measured at baseline and 12months
2. Freezing of gait assessed via the New Freezing Of Gait Questionnaire (NFOGQ) measured at baseline and 12months
3. Frailty and physical performance assessed via Short Physical Performance Battery (SPPB), gait speed and frailty status measured at baseline and 12months
4. Cognition assessed via Montreal Cognitive Assessment (MoCA) measured at baseline and 12months
5. Depression assessed via Geriatric Depression Scale (GDS) measured at baseline and 12months
6. Fear of falling assessed via the Iconographical Fall Efficacy Scale (ICON-FES) measured at baseline and 12months
7. Dysphagia assessed via the Swallowing Disturbance Questionnaire (SDQ) measured at baseline and 12months
8. Participant health-related quality of life assessed via the EuroQoL 5D-5L health status questionnaire (EQ-5D-5L) measured at baseline, 1 month, 3 months, 6 months, 9 months and 12months
9.Capability of older people assessed via the ICEpop CAPability measure for Older people (ICECAP-O) measured at baseline and 12 months
10. Mortality (all cause and PD related) through Office of National Statistics measured at 12months
11. Cost-effectiveness and NHS resource use through EQ-5D-5L and NHS Episode Statistics (HES) data

Secondary outcome via CHIEF-PD carer study:
12. Care-related quality of life via the Carer Experience Scale (CES) measured at baseline and 12months

Overall trial start date

01/04/2018

Overall trial end date

30/12/2022

Reason abandoned (if study stopped)

Eligibility

Participant inclusion criteria

Current participant inclusion criteria as of 05/07/2019:
1. Diagnosis of idiopathic Parkinson’s disease
2. Modified Hoehn and Yahr stage 1-4 disease
3. Have experienced a fall in the previous year
4. Able to walk ≥10m without aids or assistance
5. 18 years of age or above

Previous participant inclusion criteria:
1. Diagnosis of idiopathic Parkinson’s disease
2. Modified Hoehn and Yahr stage 1-4 disease
3. Have experienced a fall in the previous year
4. Able to walk ≥10m without aids or assistance

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 600; UK Sample Size: 600

Participant exclusion criteria

Current participant exclusion criteria as of 05/07/2019:
1. Previous ChEi use in 12 months prior to enrolment.
2. Hypersensitivity to rivastigmine
3. Dementia diagnosed according to Movement Disorder Society (MDS) criteria
4. Inability to attend or comply with treatment or follow-up scheduling
5. Non-English-speaking patients (cognitive tests performed in English)
6. Falling ≥ 4x per day
7. Unwillingness to use an acceptable method of contraception for the duration of the trial if they are of childbearing potential
8. Pregnant of breast feeding

Previous participant exclusion criteria:
1. Previous ChEi use in 12 months prior to enrolment
2. Hypersensitivity to rivastigmine
3. Dementia diagnosed according to Movement Disorder Society (MDS) criteria
4. Inability to attend or comply with treatment or follow-up scheduling
5. Non-English-speaking patients (cognitive tests performed in English)
6. Falling ≥ 4x per day
7. Unwillingness to use an acceptable method of contraception for the duration of the trial if they are of childbearing potential

Recruitment start date

02/09/2019

Recruitment end date

02/09/2021

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Royal United Hospitals Bath NHS Foundation Trust
Combe Park
Bath
BA1 3NG
United Kingdom

Trial participating centre

Salford Royal NHS Foundation Trust
Stott Lane
Salford
M6 8HD
United Kingdom

Trial participating centre

Northern Care Alliance
North Manchester General Hospital Delaunays Road Crumpsall
Manchester
M8 5RB
United Kingdom

Trial participating centre

Royal Cornwall Hospitals NHS Trust
Royal Cornwall Hospital Treliske
Truro
TR1 3LJ
United Kingdom

Trial participating centre

NHS Lothian
Waverley Gate 2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom

Trial participating centre

Derby Teaching Hospitals NHS Foundation Trust
Royal Derby Hospital Uttoxeter Road
Derby
DE22 3NE
United Kingdom

Trial participating centre

Plymouth Hospitals NHS Trust
Derriford Hospital Derriford Road
Plymouth
PL6 8DH
United Kingdom

Trial participating centre

Imperial College Healthcare NHS Trust
St. Marys Hospital Praed Street
London
W2 1NY
United Kingdom

Trial participating centre

Yeovil District Hospital NHS Foundation Trust
Yeovil District Hospital Higher Kingston
Yeovil
BA21 4AT
United Kingdom

Trial participating centre

The Newcastle Upon Tyne Hospitals NHS Foundation Trust
Freeman Hospital Freeman Road High Heaton
Newcastle-upon-Tyne
NE7 7DN
United Kingdom

Trial participating centre

Taunton And Somerset NHS Foundation Trust
Musgrove Park Hospital
Taunton
TA1 5DA
United Kingdom

Trial participating centre

Cambridge University Hospitals NHS Foundation Trust
Addenbrookes Hospital Hills Road
Cambridge
CB2 0QQ
United Kingdom

Trial participating centre

Royal Devon And Exeter NHS Foundation Trust
Royal Devon & Exeter Hospital Barrack Road
Exeter
EX2 5DW
United Kingdom

Trial participating centre

The Walton Centre NHS Foundation Trust
Lower Lane
Liverpool
L9 7LJ
United Kingdom

Trial participating centre

University College London Hospitals NHS Foundation Trust
250 Euston Road
London
NW1 2PG
United Kingdom

Trial participating centre

Barking, Havering and Redbridge University Hospitals NHS Trust Rom Valley Way, Romford, RM7 0AG
Rom Valley Way
Romford
RM7 0AG
United Kingdom

Trial participating centre

Gateshead NHS Foundation Trust
Queen Elizabeth Avenue
Gateshead
NE9 6SX
United Kingdom

Trial participating centre

Great Western Hospitals NHS Foundation Trust
Marlborough Road
Swindon
SN3 6BB
United Kingdom

Trial participating centre

NHS Tayside
230 Clepington Road
Dundee
DD2 1UB
United Kingdom

Trial participating centre

Nottingham University Hospitals NHS Trust
Hucknall Road
Nottingham
NG5 1PB
United Kingdom

Trial participating centre

Oxford University Hospitals NHS Foundation Trust
Headley Way Headington
Oxford
OX3 9DU
United Kingdom

Trial participating centre

Cwm Taf Morgannwg University Health Board
Princess of Wales Hospital Coity Rd
BrIdgend
CF31 1RY
United Kingdom

Trial participating centre

Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Castle Lane East
Bournemouth
BH7 7DW
United Kingdom

Trial participating centre

University Hospitals Coventry and Warwickshire NHS Trust
Clifford Bridge Rd
Coventry
CV2 2DX
United Kingdom

Trial participating centre

Northumbria Healthcare NHS Foundation Trust
Unit 7-8 Silver Fox Way Cobalt Business Park Silver Fox Way
Newcastle upon Tyne
NE27 0QJ
United Kingdom

Trial participating centre

Leeds Teaching Hospitals NHS Trust
Great George Street
Leeds
LS1 3EX
United Kingdom

Sponsor information

Organisation

University of Bristol

Sponsor details

Research and Enterprise Development
One Cathedral Square
Bristol
BS1 5DD
United Kingdom
0117 42 84021
research-governance@bristol.ac.uk

Sponsor type

University/education

Website

www.bristol.ac.uk

Funders

Funder type

Government

Funder name

NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC); Grant Codes: N/K

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal, conference presentation, publication on website, submission to regulatory authorities

IPD sharing statement:
The current data sharing plans for this study are unknown and will be available at a later date

Intention to publish date

30/12/2023

Participant level data

To be made available at a later date

Basic results (scientific)

Publication list

Publication citations

Additional files

Editorial Notes

20/04/2020: Due to current public health guidance, recruitment for this study has been paused. The Intervention Phase has been changed from "Not Applicable" to "Phase III". 05/12/2019: The following changes were made to the trial record: 1. The interventions were changed. 2. The secondary outcome measures were changed. 3. The trial participating centres "Southern Health NHS FT, Kings College NHS FT, Worcester Acute NHS Trust" were removed. 4. The trial participating centres "University Hospitals Coventry and Warwickshire NHS Trust, Northumbria Healthcare NHS Foundation Trust, Leeds Teaching Hospitals NHS Trust" were added. 05/07/2019: The following changes were made to the trial record: 1. The ethics approval date was added. 2. The participant inclusion criteria were changed. 3. The participant exclusion criteria were changed. 4. The trial participating centres "Barking, Havering and Redbridge University Hospitals NHS Trust; Gateshead NHS Foundation Trust; Great Western Hospitals NHS Foundation Trust; NHS Tayside; Nottingham University Hospitals NHS Trust; Oxford University Hospitals NHS Foundation Trust; Princess of Wales Hospital; Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust; Worcestershire Acute Hospitals NHS Trust" were added. 5. The name of trial participating centre "Pennine Acute Hospitals NHS Foundation Trust" was changed to "Northern Care Alliance" 6. The trial participating centres "Northumbria Healthcare NHS Foundation Trust; Gloucestershire Hospitals NHS Foundation Trust; North Bristol NHS Trust; South Tees Hospitals NHS Foundation Trust; Brighton And Sussex University Hospitals NHS Trust; University Hospitals Bristol NHS Foundation Trust; Betsi Cadwaladr University LHB; Northumberland Tyne and Wear NHS Foundation Trust; Abertawe Bro Morgannwg University LHB; Cardiff & Vale University LHB" were removed. 07/06/2019: Internal review. 18/04/2019: Internal review.