Clinical trial NCT04226248: CHIEF-PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson's Disease)
Official title: 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 type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Parkinson Disease
Keywords: Parkinson Disease
Parkinson
Rivastigmine
Falls
Cholinesterase Inhibitors
Phase III
Lead sponsor: University of Bristol
Sponsor class: OTHER
Collaborators: name: Royal United Hospitals Bath NHS Foundation Trust
First posted: 2020-01-13
Enrollment: 600
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A Phase III Randomised Controlled Trial of Rivastigmine versus Placebo
Primary purpose: PREVENTION

Brief summary: 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.

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. 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. If successful, this treatment in Parkinson's disease, would tackle one of the most disabling complications of the disease and positive findings will provide robust evidence to change clinical practice.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of idiopathic Parkinson's disease.
* Modified Hoehn and Yahr stage 1-4 disease as determined at baseline visit.
* Have experienced a fall in the previous year.
* Able to walk ≥10m without aids or assistance.
* 18+ years of age.

Exclusion Criteria:

* Previous ChEi use in 12 months prior to enrolment.
* Hypersensitivity to rivastigmine
* Dementia diagnosed according to MDS criteria (6).
* Inability to attend or comply with treatment or follow-up scheduling.
* Non-English-speaking patients (cognitive tests performed in English).
* Falling ≥4x per day.
* Unwillingness to use an acceptable method of contraception for the duration of the trial if they are of childbearing potential.
* Pregnancy and/or breastfeeding

Primary outcomes:
measure: Fall rate
timeFrame: 12 months from the day the IMP is commenced
Secondary outcomes:
measure: Parkinson's Disease (PD)
timeFrame: 12 months
measure: Freezing of gait
timeFrame: 12 months
measure: Frailty
timeFrame: 12 months
measure: Physical performance
timeFrame: 12 months
measure: Freezing of Gait Assessment
timeFrame: 12 months
measure: Gait Assessment
timeFrame: 12 months
measure: Cognition
timeFrame: 12 months
measure: Depression
timeFrame: 12 months
measure: Fear of falling
timeFrame: 12 months
measure: Dysphagia
timeFrame: 12 months
measure: Participant health related quality of life
timeFrame: 0,1,3,6 9 and 12 months
measure: Capability of older people
timeFrame: 12 months
measure: Mortality (all cause and PD-related)
timeFrame: 12 months
measure: Cost effectiveness by NHS resource use
timeFrame: 12 months
measure: Apathy
timeFrame: 12 months
Other outcomes:
Locations:
city: Romford
country: United Kingdom
facility: Barking, Havering and Redbridge University Hospitals NHS trust
state: Accepted
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
state: England
city: Bangor
country: United Kingdom
facility: Betsi Cadwaladr University Health Board
state: Gwynedd
city: Norwich
country: United Kingdom
facility: Norfolk and Norwich University Hospital
state: Norfolk
city: Edinburgh
country: United Kingdom
facility: Lothian Health Board NHS
state: Scotland
city: Larbert
country: United Kingdom
facility: NHS Forth Valley
state: Scotland
city: Bath
country: United Kingdom
facility: Royal United Hospitals Bath NHS Foundation Trust
state: Somerset
city: Aberdeen
country: United Kingdom
facility: NHS Grampian
city: Barnsley
country: United Kingdom
facility: Barnsley Hospital NHS Foundation Trust
city: Bournemouth
country: United Kingdom
facility: University Hospitals Dorset NHS Foundation Trust
city: Bridgend
country: United Kingdom
facility: Princess of Wales Hospital (Cwm Taf Morgannwg University Health Board)
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol and Weston NHS Foundation Trust
city: Bristol
country: United Kingdom
facility: North Bristol NHS Trust
city: Bury
country: United Kingdom
facility: Pennine Acute Hospitals NHS Trust
city: Derby
country: United Kingdom
facility: University Hospitals of Derby and Burton NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: NHS Tayside
city: Gateshead
country: United Kingdom
facility: Gateshead Health NHS Foundation Trust
city: Gloucester
country: United Kingdom
facility: Gloucestershire Hospitals NHS Foundation Trust
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospitals NHS Trust
city: Leicester
country: United Kingdom
facility: University Hospitals of Leicester NHS Foundation Trust
city: Liverpool
country: United Kingdom
facility: The Walton Centre NHS Foundation Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Middlesbrough
country: United Kingdom
facility: South Tees Hospitals NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Northumbria Healthcare NHS Foundation Trust
city: Newcastle
country: United Kingdom
facility: Newcastle Hospitals NHS Foundation Trust
city: Newport
country: United Kingdom
facility: Aneurin Bevan University Health Board
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals
city: Peterborough
country: United Kingdom
facility: North West Anglia NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
city: Preston
country: United Kingdom
facility: Lancashire Teaching Hospitals NHS Foundation Trust
city: Reading
country: United Kingdom
facility: Royal Berkshire NHS Foundation Trust
city: Salford
country: United Kingdom
facility: Salford Royal NHS Foundation Trust
city: Stockton-on-Tees
country: United Kingdom
facility: North Tees and Hartlepool Hospitals NHS Foundation Trust
city: Taunton
country: United Kingdom
facility: Somerset NHS Foundation Trust
city: Wigan
country: United Kingdom
facility: Wrightington, Wigan and Leigh Teaching Hospitals NHS Foundation Trust
city: Wrexham
country: United Kingdom
facility: Betsi Cadwaladr University Health Board
city: Yeovil
country: United Kingdom
facility: Yeovil District Hospital
Study officials:
affiliation: University of Bristol
name: Emily Henderson, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Neumann S, Taylor J, Bamford A, Metcalfe C, Gaunt DM, Whone A, Steeds D, Emmett SR, Hollingworth W, Ben-Shlomo Y, Henderson EJ. Cholinesterase inhibitor to prevent falls in Parkinson's disease (CHIEF-PD) trial: a phase 3 randomised, double-blind placebo-controlled trial of rivastigmine to prevent falls in Parkinson's disease. BMC Neurol. 2021 Oct 29;21(1):422. doi: 10.1186/s12883-021-02430-2.