Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02098824
Recruitment Status : Unknown
Verified April 2016 by Dr. Niels Prins, MD, PhD, VU University Medical Center.
Recruitment status was:  Recruiting
First Posted : March 28, 2014
Last Update Posted : May 2, 2016
Sponsor:
Information provided by (Responsible Party):
Dr. Niels Prins, MD, PhD, VU University Medical Center

Brief Summary:
Single center threeway double blind cross over trial investigating the pharmacological responsivity in patients with VCI using a challenge aimed at the monoaminergic and cholinergic neuronal systems

Condition or disease Intervention/treatment Phase
Mild Cognitive Impairment (Vascular) Mild Cognitive Disorder (Vascular) Vascular Dementia Drug: Galantamine Drug: Methylphenidate Drug: Placebo Phase 2 Phase 3

Detailed Description:

Vascular Cognitive Impairment is an important cause of cognitive impairment and dementia. 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 executive 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.

The investigators 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. They will also undergo MRI, including diffusion tensor imaging MRI (DTI)/'fiber tracking'; and resting state (RS) functional MRI (fMRI). In a double-blind, three-way, case cross over trial, the investigators will study the effects of methylphenidate on executive function and of galantamine on episodic memory function. During three separate visits, patients will receive the pharmacological interventions (placebo, methylphenidate, and galantamine) at the investigators Clinical Research Unit. Also, during a study day the investigators will collect blood samples at different timepoints.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Official Title: Symptomatic Treatment of Vascular Cognitive Impairment
Study Start Date : February 2014
Estimated Primary Completion Date : December 2016
Estimated Study Completion Date : July 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Galantamine
Single administration of capsule containing 16 mg Galantamine
Drug: Galantamine
Single administration of capsule containing 16 mg of Galantamine
Other Name: Reminyl

Placebo Comparator: Placebo
Single oral administration of capsule containing placebo
Drug: Placebo
Single administration of capsule containing placebo

Active Comparator: Methylphenidate
Single administration of capsule containing 10 mg Methylphenidate
Drug: Methylphenidate
Single administration of capsule containing 10 mg of Methylphenidate
Other Name: Ritalin




Primary Outcome Measures :
  1. Change on performance on executive function and on memory after active challenge [ Time Frame: timepoints 1 hour, 2.5 hours and 3.5 hours ]
    Patients will perform multiple Neurocart tests: eye movement recording, pharmaco-EEG's, visual verbal language test (VVLT), Adaptive Tracker, Facial Recognition taks, N-back and Stop Signal test of which the Adaptive Tracker and VVLT have the main focus.


Secondary Outcome Measures :
  1. Change on performance on other Neurocart tests after active challenge [ Time Frame: Timepoints 1.0 hour, 2.5 hours and 3.5 hours ]
    Change of performance on the other tests: N-back, Facial recognition task, Stop Signal task, eye movements and pharmaco-EEG


Other Outcome Measures:
  1. Locations and number of cerebrovascular lesions [ Time Frame: Single MRI scan after screening ]
    If patients are suitable for the study and have signed the informed consent they will undergo a MRI (structural, DTI and RS-fMRI). Visual assessment of structural cerebrovascular lesions in each patients

  2. Structural connectivity of white matter tracts [ Time Frame: Single MRI after screening ]
    If patients are suitable for the study and have signed the informed consent they will undergo a MRI (structural, DTI and RS-fMRI). Assessment of structural connectivity of specific white matter tracts, known to be part of the cholinergic and monoaminergic system with FLS software

  3. Functional connectivity in resting state networks [ Time Frame: Single MRI, after screening ]
    If patients are suitable for the study and have signed the informed consent they will undergo a MRI (structural, DTI and RS-fMRI). Assessment functional connectivity in specific resting state networks

  4. Maximum concentration (Cmax) [ Time Frame: t-1.5, t=1, t=2.5, t=3.5 ]
  5. Time of Cmax (Tmax) [ Time Frame: t=-1.5, t=1, t=2.5, t=3.5 ]
  6. Area under the Curve [ Time Frame: t=-1.5, t=1, t=2.5,t=3.5 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Outpatients
  • Objective executive dysfunction and/or memory impairment on neuropsychological tests and imaging evidence of cerebrovascular disease (white matter changes (Fazekas ≥2, (lacunar) infarcts)
  • Mini Mental State Examination (MMSE) ≥16
  • Clinical Dementia Rating Score (CDR of 0.5-1)
  • No contraindication for treatment with a Cholinesterase inhibitor (CEI) or Methylphenidate (MPH) (www.fk.cvz.nl)
  • Assessed by the treating neurologist as mentally capable of understanding the implications of study participation
  • Presence of an informant/caregiver at the information visit, signing of informed consent, and all study visits

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 on the study day until the end of the study day
  • Other causes that can explain cognitive symptoms including but not limited to: delirium, multiple sclerosis, amyotrophic lateral sclerosis, progressive supranuclear palsy, mental retardation, infectious encephalitis that led to persistent cognitive deficits or head trauma with loss of consciousness that led to persistent cognitive deficits
  • Use of neuroleptics
  • Use of celiprolol or sotalol
  • Use of MAO-A/B inhibitors
  • Current use of centrally acting anticholinergics (e.g. oxybutynin, 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 patients are on a stable dose without any recent or upcoming changes
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02098824


Contacts
Layout table for location contacts
Contact: Niels D Prins, MD,PhD +20 3017170 nd.prins@vumc.nl
Contact: Jolien F Leijenaar, MD, MSc +204440183 j.leijenaar@vumc.nl

Locations
Layout table for location information
Netherlands
VU University Medical Center Recruiting
Amsterdam, Netherlands, 1081 HV
Contact: Niels D Prins, MD, PhD    +20 3017170    nd.prins@vumc.nl   
Sub-Investigator: Jolien F Leijenaar, MD, MSc         
Sponsors and Collaborators
VU University Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Niels D Prins, MD, PhD VUmc

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Dr. Niels Prins, MD, PhD, MD, PhD, VU University Medical Center
ClinicalTrials.gov Identifier: NCT02098824     History of Changes
Other Study ID Numbers: NL45933.029.13
First Posted: March 28, 2014    Key Record Dates
Last Update Posted: May 2, 2016
Last Verified: April 2016
Keywords provided by Dr. Niels Prins, MD, PhD, VU University Medical Center:
vascular cognitive impairment
treatment
cerebrovascular lesions
memory impairment
executive dysfunction
neuronal networks
white matter tracts
monoaminergic systems
cholinergic systems
DTI
rs-fMRI
Additional relevant MeSH terms:
Layout table for MeSH terms
Dementia, Vascular
Cognitive Dysfunction
Cognition Disorders
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Methylphenidate
Galantamine
Central Nervous System Stimulants
Physiological Effects of Drugs
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents
Cholinesterase Inhibitors
Enzyme Inhibitors
Cholinergic Agents