Study of Rivastigmine to Treat Parkinsonian Apathy Without Dementia

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

Apathy usually refers to a set of behavioural, emotional and cognitive features as a reduced interest and participation in main activities of daily life, a lack of initiative, a trend toward an early withdrawal from started activities, an indifference and a flattening of affect. We have validated a new specific scale (Lille Apathy Rating Scale, LARS) in order to detect and quantify apathy in Parkinson's disease (PD). Apathy was shown to be frequent in PD with a prevalence of 32%. It has suggested that the medial frontal and limbic cholinergic deficits may underlie apathy in neurodegenerative disorders like Alzheimer's disease (AD). Such a hypothesis is supported by recent evidence indicating the beneficial effects of cholinesterase inhibitors on neuropsychiatric symptoms, mainly apathy, in AD patients. As the efficacy of rivastigmine on cognition has also been shown in PD, we aimed to assess with a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial, the efficacy and acceptability of a 6 months treatment with rivastigmine on apathy in 60 patients with PD without dementia. The primary end point will be the LARS score and the secondary end points will be the cognitive, behavioural and motor symptoms of PD. Two add-on studies will be proposed: first the measure of choline and glutamate peaks on Magnetic Resonance Spectrometry focused on the structures implicated in apathy in order to give insights in the physiopathological mechanisms of the treatment. Secondly, the recording of the REM sleep behavior disorders in relation with the cholinergic part of the pedunculopontine nucleus. Regarding that apathy could be one of the first steps toward PD dementia, treating very early could have substantial implications on the patients and their caregiver.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Lille
• Treatments: Cholinesterase Inhibitors; Rivastigmine

Criteria

Inclusion criteria:

• Clinical diagnosis of Parkinson's disease: Gibb and Gelb criteria

• Apathy defined by a score of - 16 or more on the LARS scale (Sockeel et al., 2006)and criteria of Marin (1991)

• No dementia according to DSM IV with MMSE Score≥ 27 and Mattis score≥ 130

• Under stable dopaminergic treatment for 3 months

Exclusion criteria:

• Depression according to DSM-IV criteria and a score < 18 on the MADRS

• Subthalamic stimulation of less than one year

• Subthalamic stimulation without stable parameters for 3 months

• Subject older than 80 years

• Severe rest tremor with a subscore > or= 3 on the UPDRS part

• Parkinson related Psychosis in progress

• Hypersensibility to cholinesterase inhibitors or carbamates

• Myocardial infarction, other cardiac affections

• Severe hepatic insufficiency

• Sever medical illness

• Skin diseases interfering with transdermal patch

• Pregnancy

• Incapacity to give the consent