CHIEF PD (CHolinesterase Inhibitor to prEvent Falls in Parkinson's Disease)

Study Overview
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Brief Summary
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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.

Official Title
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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.

Conditions
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Parkinson Disease

Intervention / Treatment
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* Drug: Rivastigmine Transdermal System
* Other: Placebo Transdermal System


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A Phase III Randomised Controlled Trial of Rivastigmine versus Placebo
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active (Rivastigmine)<br>Rivastigmine Transdermal Patches | Drug: Rivastigmine Transdermal System<br>* Rivastigmine Trandermal Patches applied once a day for up to 12 months<br>|
| Placebo Comparator: Placebo<br>Placebo Matched Transdermal Patches | Other: Placebo Transdermal System<br>* Placebo Trandermal Patches applied once a day for up to 12 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fall rate | Fall rate measured using monthly diaries and telephone calls prospectively | 12 months from the day the IMP is commenced | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Parkinson's Disease (PD) | MDS-UPDRS total score in the practically defined 'ON' state and each individual subscale (1-4) | 12 months | 
| Freezing of gait | New Freezing of Gait Questionnaire (NFOGQ) | 12 months | 
| Frailty | Frailty assessed by the SHARE-FI | 12 months | 
| Physical performance | Measured by the Short physical performance battery (SPPB) | 12 months | 
| Freezing of Gait Assessment | Gait speed measured with Freezing of Gait (turn test) | 12 months | 
| Gait Assessment | Gait speed measured with and without dual task | 12 months | 
| Cognition | Montreal Cognitive Assessment (MoCA) | 12 months | 
| Depression | Geriatric Depression Scale (GDS) | 12 months | 
| Fear of falling | Iconographical Fall Efficacy Scale (ICON-FES) | 12 months | 
| Dysphagia | Swallowing Disturbance Questionnaire (SDQ) | 12 months | 
| Participant health related quality of life | EuroQoL 5D-5L health status questionnaire (EQ-5D-5L) | 0,1,3,6 9 and 12 months | 
| Capability of older people | ICEpop CAPability measure for Older people (ICECAP-O) | 12 months | 
| Mortality (all cause and PD-related) | Office of National Statistics (ONS) data | 12 months | 
| Cost effectiveness by NHS resource use | NHS Hospital Episode Statistics (HES) data | 12 months | 
| Apathy | Starkstein Apathy Scale | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Parkinson, Parkinson Disease, Rivastigmine, Cholinesterase Inhibitors, Phase III, Falls