A trial of rivastigmine to prevent falls in Parkinson's
| ISRCTN | ISRCTN41639809 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN41639809 |
| EudraCT/CTIS number | 2018-003219-23 |
| IRAS number | 235625 |
| ClinicalTrials.gov number | NCT04226248 |
| Secondary identifying numbers | CPMS 40906, IRAS 235625 |
- Submission date
- 08/04/2019
- Registration date
- 16/04/2019
- Last edited
- 23/08/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
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?
April 2018 to July 2024
Who is funding the study?
NIHR Evaluation, Trials and Studies Co-ordinating Centre (NETSCC)
Who is the main contact?
CHIEF-PD Trial Management Team, Chief-pd@bristol.ac.uk
Contact information
Scientific
Population Health Sciences
Bristol Medical School
University of Bristol
G11, 1-5 Whiteladies Road
Bristol
BS8 1NU
United Kingdom
| Phone | +44 (0)117 4283111 |
|---|---|
| Chief-pd@bristol.ac.uk |
Study information
| Study design | Randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| 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 |
| Study acronym | CHIEF-PD |
| Study hypothesis | Cholinesterase inhibitor (ChEi) treatment prevents people with Parkinson's from falling and is cost-effective. |
| Ethics approval(s) |
Approved 17/05/2019, Southwest Central Bristol Research Ethics Committee (Health Research Authority, Whitefriars, Level 3 Block B, Lewins Mead, Bristol, BS1 2NT, United Kingdom; +44 (0)2071048046; nrescommittee.southwest-bristol@nhs.net), ref: 19/SW/0043 |
| 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 |
| Pharmaceutical study type(s) | |
| Phase | Phase III |
| Drug / device / biological / vaccine name(s) | 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 study start date | 01/04/2018 |
| Overall study end date | 30/07/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 600; UK Sample Size: 600 |
| Total final enrolment | 600 |
| 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 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 | 30/04/2023 |
Locations
Countries of recruitment
- England
- Scotland
- United Kingdom
- Wales
Study participating centres
Bath
BA1 3NG
United Kingdom
Salford
M6 8HD
United Kingdom
Delaunays Road
Crumpsall
Manchester
M8 5RB
United Kingdom
Treliske
Truro
TR1 3LJ
United Kingdom
2-4 Waterloo Place
Edinburgh
EH1 3EG
United Kingdom
Uttoxeter Road
Derby
DE22 3NE
United Kingdom
Derriford Road
Plymouth
PL6 8DH
United Kingdom
Praed Street
London
W2 1NY
United Kingdom
Higher Kingston
Yeovil
BA21 4AT
United Kingdom
Freeman Road
High Heaton
Newcastle-upon-Tyne
NE7 7DN
United Kingdom
Taunton
TA1 5DA
United Kingdom
Hills Road
Cambridge
CB2 0QQ
United Kingdom
Barrack Road
Exeter
EX2 5DW
United Kingdom
Liverpool
L9 7LJ
United Kingdom
London
NW1 2PG
United Kingdom
Romford
RM7 0AG
United Kingdom
Gateshead
NE9 6SX
United Kingdom
Swindon
SN3 6BB
United Kingdom
Dundee
DD2 1UB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Headington
Oxford
OX3 9DU
United Kingdom
Coity Rd
BrIdgend
CF31 1RY
United Kingdom
Bournemouth
BH7 7DW
United Kingdom
Coventry
CV2 2DX
United Kingdom
Silver Fox Way
Newcastle upon Tyne
NE27 0QJ
United Kingdom
Leeds
LS1 3EX
United Kingdom
Barnsley
S75 2EP
United Kingdom
Colney
Norwich
NR4 7UY
United Kingdom
Southmead Road
Bristol
BS10 5NB
United Kingdom
London
E9 6SR
United Kingdom
Ysbyty Gwynedd
Penrhosgarnedd
Bangor
LL57 2PW
United Kingdom
Gloucester
GL1 3NN
United Kingdom
Level 3, Balmoral Building
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Sponsor information
University/education
Research and Enterprise Development
One Cathedral Square
Bristol
BS1 5DD
England
United Kingdom
| Phone | +44 (0)117 42 84021 |
|---|---|
| research-governance@bristol.ac.uk | |
| Website | https://www.bristol.ac.uk/ |
"ROR" |
https://ror.org/0524sp257 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 28/02/2025 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal, conference presentation, publication on website, submission to regulatory authorities |
| IPD sharing plan | The current data sharing plans for this study are unknown and will be available at a later date |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 29/10/2021 | 15/02/2023 | Yes | No | |
| HRA research summary | 26/07/2023 | No | No |
Editorial Notes
23/08/2024: The intention to publish date was changed from 31/12/2024 to 28/02/2025. Total final enrolment added.
03/04/2024: The following updates have been made:
1. Study website was amended.
2. The study contact was amended.
3. IRAS number added.
15/02/2023: The following updates have been made to the study record and the plain English summary updated accordingly:
1. The recruitment end date has been changed from 30/04/2022 to 30/04/2023.
2. The overall trial end date has been changed from 30/12/2022 to 30/07/2024.
3. The intention to publish date has been changed from 30/12/2023 to 31/12/2024.
4. Publication reference added.
22/11/2021: The following changes have been made:
1. The recruitment end date has been changed from 30/11/2021 to 30/04/2022.
2. Barnsley Hospital NHS Foundation Trust, Norfolk and Norwich University Hospitals NHS Foundation Trust, North Bristol NHS Trust, Homerton University Hospital NHS Foundation Trust, Betsi Cadwaladr University Health Board, Gloucestershire Hospitals NHS Foundation Trust and University Hospitals Of Leicester NHS Trust have been added to the trial participating centres.
13/09/2021: The recruitment end date has been changed from 02/09/2021 to 30/11/2021.
08/02/2021: The following changes were made to the trial record:
1. The recruitment resumed.
2. The clincaltrials.gov number was added.
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.
