investigate whether early treatment with ChEI delays the progression of minor VH to major VH without insight or PDP. In addition, we will measure motor control, psychotic symptoms, cognitive impairment, mood disorders, adverse events and compliance…
ID
Source
Brief title
Condition
- Movement disorders (incl parkinsonism)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary outcome measure is the median time until PD patients with minor VH
progress to major VH without insight. The clinical endpoint is defined as the
start with antipsychotic treatment.
Secondary outcome
Secondary outcome measures are changes in motor control, psychotic symptoms,
cognitive impairment, mood disorders, daytime sleepiness, cholinergic
deficiency, the number of adverse events, compliance, disability and caregiver
burden. All relevant costs will be measured and valued.The median time until PD
patients with minor VH progress to PD dementia is measured by means of changes
in cognitive function. The secondary neurophysiological outcome measures are
peak frequency, functional connectivity, topological network organisation and
the direction of information flow. All relevant costs will be measured and
valued.
Background summary
Visual hallucinations (VH) are the most common non-motor symptoms in
Parkinson*s disease (PD). As an independent predictor for cognitive decline and
nursing home placement they form an important disability milestone in the
course of PD. According to current clinical guidelines minor VH do not require
treatment per se. But as minor VH precede the stage of major VH without insight
and PD associated psychosis (PDP) they offer an opportunity for early
intervention. Neuroleptic drugs delay the transition into PDP but are
unsuitable for early treatment of VH due to their side effects. We hypothesize
that cholinesterase inhibitors (ChEI) are a well-tolerated alternative for the
early treatment of minor VH to delay the progression to PDP and that brain
network analysis is suitable to predict treatment response.
Study objective
investigate whether early treatment with ChEI delays the progression of minor
VH to major VH without insight or PDP. In addition, we will measure motor
control, psychotic symptoms, cognitive impairment, mood disorders, adverse
events and compliance, disability, caregiver burden and care use. We assess the
cost-effectiveness of early chronic treatment of VH with ChEI. Finally, we
analyse changes of functional brain networks before and during treatment.
Study design
a randomized, double blind, placebo-controlled, multi-center trial with an
economic evaluation.
Intervention
rivastigmine capsule 6 mg BID or placebo BID for 24 months
Study burden and risks
The burden of participation consists of a total of 5 clinical visits (every 6
months), 4 telephone interviews on adverse events during the escalation phase
and 9 internet questionnaires (every 3 months). Once12 ml blood will be drawn.
In a subgroup 3 additional visits in the first year are needed for EEG
recording. There is a risk for adverse reactions with rivastigmine treatment;
the most common are nausea and vomiting.
De Boelelaan 1118
Amsterdam 1081 HZ
NL
De Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
1. idiopathic PD with bradykinesia and at least two of the following signs; resting tremor, rigidity, and asymmetry (in accordance with clinical diagnostic criteria of the UK PD Society Brain Bank);;2. the presence of minor visual hallucinations for at least 4 weeks, defined by a score of 1 or 2 on the hallucinations item of the Unified Parkinson*s Disease rating Scale (UPDRS)1-MDS;;3. age 40 years and over.
Exclusion criteria
1. Parkinson's disease associated psychosis, defined as the need for antipsychotic drug treatment in the opinion of the treating neurologist;;2. Parkinson's disease dementia, defined by a score of 26 or lower on the Mini Mental State Examination (MSSE);;3. current delirium (caused by infection or metabolic disturbance);;4. current treatment with drugs that have important central anticholinergic effects;5. current or recent (< 6 months) treatment with Cholinesterase inhibitors, such as rivastigmine (Exelon) or galantamine (Reminyl);;6. VH in response (<= 1 month) to increase of dopamingergic treatment;;7. history of psychosis, (known) sick sinus syndrome or other arrhythmia ;8. current severe ophtalmologic disease (defined as a visual acuity score of < 0.5 based on Snellen eye test';;9. permanent stay in a nursing home;;10. no informed consent.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2013-001722-25-NL |
| ClinicalTrials.gov | NCT01856738 |
| CCMO | NL44622.029.13 |