Symptomatic Treatment of Vascular Cognitive Impairment

NCT02098824 | Unknown Phase 2 DMC

• 1 other identifier: NL45933.029.13
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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

Conditions

Mild Cognitive Impairment (Vascular); Mild Cognitive Disorder (Vascular); Vascular Dementia

Keywords

vascular cognitive impairment; treatment; cerebrovascular lesions; memory impairment; executive dysfunction; neuronal networks; white matter tracts; monoaminergic systems; cholinergic systems; DTI; rs-fMRI

Outcome Measures

Primary Outcomes (1)

• Change on performance on executive function and on memory after active challenge

  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.

  timepoints 1 hour, 2.5 hours and 3.5 hours

Secondary Outcomes (1)

• Change on performance on other Neurocart tests after active challenge

  Timepoints 1.0 hour, 2.5 hours and 3.5 hours

Other Outcomes (6)

• Locations and number of cerebrovascular lesions

  Single MRI scan after screening

• Structural connectivity of white matter tracts

  Single MRI after screening

• Functional connectivity in resting state networks

  Single MRI, after screening

Study Arms (3)

Galantamine

ACTIVE COMPARATOR

Single administration of capsule containing 16 mg Galantamine

Drug: Galantamine

Placebo

PLACEBO COMPARATOR

Single oral administration of capsule containing placebo

Drug: Placebo

Methylphenidate

ACTIVE COMPARATOR

Single administration of capsule containing 10 mg Methylphenidate

Drug: Methylphenidate

Interventions

Galantamine DRUG

Single administration of capsule containing 16 mg of Galantamine

Also known as: Reminyl

Galantamine

Methylphenidate DRUG

Single administration of capsule containing 10 mg of Methylphenidate

Also known as: Ritalin

Methylphenidate

Placebo DRUG

Single administration of capsule containing placebo

Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Amsterdam UMC, location VUmc: lead

Study Sites (1)

VU University Medical Center

Amsterdam, 1081 HV, Netherlands

RECRUITING

Related Publications (2)

• Leijenaar JF, Groeneveld GJ, Klaassen ES, Leeuwis AE, Scheltens P, Weinstein HC, van Gerven JMA, Barkhof F, van der Flier WM, Prins ND. Methylphenidate and galantamine in patients with vascular cognitive impairment-the proof-of-principle study STREAM-VCI. Alzheimers Res Ther. 2020 Jan 7;12(1):10. doi: 10.1186/s13195-019-0567-z.

  PMID: 31910895 DERIVED

• Leijenaar JF, Groeneveld GJ, van der Flier WM, Scheltens P, Klaassen ES, Weinstein HC, Biessels GJ, Barkhof F, Prins ND. Symptomatic Treatment of Vascular Cognitive Impairment (STREAM-VCI): Protocol for a Cross-Over Trial. JMIR Res Protoc. 2018 Mar 20;7(3):e80. doi: 10.2196/resprot.9192.

  PMID: 29559423 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Neurocognitive Disorders; Dementia, Vascular; Memory Disorders

Interventions

Galantamine; Methylphenidate

Condition Hierarchy (Ancestors)

Cognition Disorders; Mental Disorders; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Dementia; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amaryllidaceae Alkaloids; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Niels D Prins, MD, PhD

  VUmc

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Niels D Prins, MD,PhD

CONTACT

+20 3017170; nd.prins@vumc.nl

Jolien F Leijenaar, MD, MSc

CONTACT

+204440183; j.leijenaar@vumc.nl

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 28, 2014
• Study Start: February 1, 2014
• Primary Completion: December 1, 2016
• Study Completion: July 1, 2017
• Last Updated: May 2, 2016

Record last verified: 2016-04

Locations

NL (1)