Study of Rivastigmine to Treat Parkinsonian Apathy Without Dementia

NCT00767091 | Completed Phase 3

• 2 other identifiers: 2008-002578-362008/0817
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Parkinson's Disease; Apathy; no Dementia

Keywords

Parkinson's disease; Apathy; Rivastigmine; transdermal patch; anticholinesterasic; acetylcholine

Outcome Measures

Primary Outcomes (1)

• Measure on the scale : Lille Apathy Rating Scale (LARS)

  measure of the reduction of apathy with this qualitative scale from -36 +36 with the cut off -16

  6 months

Secondary Outcomes (1)

• Cognitive, motor and behaviour assessment

  6 months

Study Arms (2)

Active treatment

ACTIVE COMPARATOR

A: transdermal rivastigmine at 4.6 mg per day during one month then 9.5 mg per day during 5 months.

Drug: rivastigmine

placebo

PLACEBO COMPARATOR

transdermal patch of placebo

Drug: placebo

Interventions

rivastigmine DRUG

transdermal patch of rivastigmine of 9.5 mg/day

Also known as: cholinesterase inhibitors (Exelon)

Active treatment

placebo DRUG

transdermal patch of placebo

Also known as: transdermal patch without active substance

placebo

Eligibility Criteria

• Age: 15 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Lille: lead

Study Sites (1)

Devos

Lille, Nord, 59037, France

Location

Related Publications (1)

• Devos D, Moreau C, Maltete D, Lefaucheur R, Kreisler A, Eusebio A, Defer G, Ouk T, Azulay JP, Krystkowiak P, Witjas T, Delliaux M, Destee A, Duhamel A, Bordet R, Defebvre L, Dujardin K. Rivastigmine in apathetic but dementia and depression-free patients with Parkinson's disease: a double-blind, placebo-controlled, randomised clinical trial. J Neurol Neurosurg Psychiatry. 2014 Jun;85(6):668-74. doi: 10.1136/jnnp-2013-306439. Epub 2013 Nov 11.

  PMID: 24218528 DERIVED

MeSH Terms

Conditions

Parkinson Disease; Lethargy

Interventions

Rivastigmine; Cholinesterase Inhibitors; Transdermal Patch

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phenylcarbamates; Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Cholinergic Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Equipment and Supplies

Study Officials

• David Devos, MD, PhD

  Department of Neurology, University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2008
• First Posted: October 6, 2008
• Study Start: March 1, 2009
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: April 24, 2012

Record last verified: 2009-03

Locations

FR (1)