Primary Objective: To study the change on performance on executive function and memory function (as measured on Neurocart), after an active challenge with methylphenidate (monoaminergic) and galantamine (cholinergic), compared to placebo, in…
ID
Source
Brief title
Condition
- Neurological disorders NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Changes in the performance on the cognitive tests as measured with the
neurocart.
Secondary outcome
DTI and RS fMRI parameters integrity on white matter tracts and neuronal
networks
Background summary
Vascular Cognitive Impairment is an important cause of cognitive impairment and
dementia. Up till now, there are no approved symptomatic treatments for
Vascular Cognitive Impairment. Research on novel pharmacological treatments
that may reduce clinical symptoms in these patients is needed. Evidence
suggests that executive dysfunction and memory impairment in Vascular Cognitive
Impairment are caused by damage to monoaminergic and cholinergic
neurotransmitter-systems, respectively. However, patients with Vascular
Cognitive Impairment form a clinically heterogeneous group, i.e. the extent to
which fexecutive function and memory are affected differs from patient to
patient. Previous intervention studies have not taken this inter-patient
variability into account. Individually tailored pharmacological interventions,
aimed at the affected neurotransmitter systems, may ameliorate cognitive
symptoms in patients with Vascular Cognitive Impairment. Using a
pharmacological challenge, it is possible to detect individual sensitivity to
specific pharmacological interventions. Furthermore, with the use of novel MRI
techniques, it is possible to correlate the location and severity of
cerebrovascular lesions to impaired structural and functional connectivity in
each subject.
Study objective
Primary Objective:
To study the change on performance on executive function and memory function
(as measured on Neurocart), after an active challenge with methylphenidate
(monoaminergic) and galantamine (cholinergic), compared to placebo, in patients
with VCI.
Secondary objective:
To study the effect of cerebrovascular lesions on structural and functional
connectivity with structural MRI, DTI *fiber tracking* and rs-fMRI in patients
with VCI.
To correlate the location and severity of cerebrovascular lesions to impaired
structural and functional connectivity in each subject. Based on this
information we aim to develop a prediction model that estimates a positive
response to a cholinergic and/or monoaminergic challenge in individual patients
with VCI.
To investigate the relationship between the cognitive profile of individual
subjects, i.e. executive dysfunction or memory impairment, and a positive
response to a specific challenge.
Study design
We will recruit 30 patients with Vascular Cognitive Impairment (according to
the criteria of the American Heart Association/American Stroke Association), at
the Alzheimer Center of the VU University Medical Center and the Utrecht
University Medical Center. Participants will receive a complete dementia
screening, including a neuropsychological and neuropsychiatric examination.
They will also undergo MRI at 3T, including DTI/*fiber tracking* and RS fMRI.
In a double-blind, three-way, case cross over trial, we will study the effects
of methylfenidate on executive function and of galantamine on episodic memory
function. During three separate visits, patients will receive the
pharmacological interventions (placebo, methylfenidate, and galantamine) at our
Clinical Research Unit. Also, during a study day we will collect blood samples
at different timepoints.
Intervention
Methylphenidate 10 mg
Galantamine 16 mg
Placebo
Study burden and risks
Patients will visit our clinical research unit four times on separate visits at
least one week apart. The first visit is meant for screening study
participation. During the study day patients will receive a single dose of
either medication or placebo. After the medication challenge they will perform
several tests on the Neurocart on several timepoints.
Since there will be a single dose adminstration and the already registered
medication in low dosage, the risk of adverse advents will be low.
During the study day blood samples will be taken via a canule. The canule might
cause a haematoma, which might cause slight discomfort.
The MRI will be performed without any contrast, this keeps the MRI burden low.
de Boelelaan 1118
Amsterdam 1081 HZ
NL
de Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
Outpatients
Objective executive dysfunction and/or memory impairment and imaging evidence of cerebrovascular disease (white matter changes (Fazekas=/>2, lacunar infarcts)
MMSE =/>16
Clinical Dementia Rating Score (CDR of 0.5-1)
No contraindication for treatment with a cholinesterase inhibitor or methylphenidate
Assessed by the treating neurologist as mentally capable of understanding the implications of study participation
Presence of an informant,/caregiver at the information visit and the signing of the informed consent
Signed informed consent by patient
Exclusion criteria
Clinically relevant history of abnormal physical or mental health interfering with the study as determined by medical history taking and physical examinations obtained during the screening visit and/or at the study day as judged by the investigator;
Clinically relevant abnormal laboratory results, electrocardiogram (ECG) and vital signs, or physical findings at screening and/or at the start of the study day (as judged by the investigator);
Unwilling to or unable to stop smoking 12 hours before study day until 12 hours after the study day
Other causes that can explain cognitive symptoms
Use of doses of corticosteroids that in the opinion of the investigator may interfere pharmacodynamic measurements performed in the study.
Use of celiprolol or sotalol
Use of neuroleptics
Current use of centrally acting anticholinergics (e.g. oxybutinin, mebeverine, ipratropium(bromide)) Use of benzodiazepine within 48 hours before a study day
Current use of a CEI (rivastigmine, galantamine, donepezil)
Alcohol abuse (defined as use of alcohol despite significant areas of dysfunction, evidence of physical dependence, and/or related hardship due to alcohol)
Use of recreational drugs
Concomitant use of inhibitors of CYP2D6 (a/o kinidine, paroxetine, fluoxetine) or of CYP3A4 (a/o ketoconazole, ritonavir) unless on a stable dose and no expected upcoming changes in dosing.
Any other condition that in the opinion of the investigator would complicate or compromise the study, or the well being of the subject.
Any contra-indication for MRI
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 | EUCTR2013-003396-35-NL |
| CCMO | NL45933.029.13 |