The Efficacy of Gliatiline® on Post-stroke Patients With Vascular Cognitive Impairment no Dementia

Study Overview
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Brief Summary
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To date, there are no approved treatments for vascular cognitive impairment (VCI) and the main therapeutic efforts are aimed at controlling vascular risk factors for countering VCI development or progression. Several studies have reported cholinergic deficits in brain and cerebrospinal fluid of patients with VCI. The effect of choline alphoscerate in clinical studies of Alzheimer's disease and VCI improved memory and attention impairments. The purpose of our study is to determine effectiveness of choline alphoscerate vs placebo in improving cognition in post-stroke patients with VCI-non dementia (VCI-ND).

Detailed Description
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Impaired brain cholinergic neurotransmission has a key role in the deterioration of cognitive functions in Alzheimer's disease and vascular cognitive impairment (VCI). These deficits, although are of different degree than those found in Alzheimer's disease, were suggested to be associated with VCI.To date, there are no approved treatments for vascular dementia(VaD)and the main therapeutic efforts in this field are aimed at controlling vascular risk factors for countering VaD development or progression. There have also been several trials of cholinesterase inhibitors for treatment of VCI. Available data suggest some evidence of benefit of cholinesterase inhibitors in subcortical vascular dementia and vascular cognitive impairment. Treated patients had modest benefits in cognition, attention, executive functioning and ability to perform instrumental activities of daily living, but the effect is too limited due to the small numbers of subjects examined and it is complex to establish the clinical relevance of these effects. The majority of clinical studies available on the effect of choline alphoscerate in neurodegenerative and cerebrovascular disorders were reviewed. A comparison of Alzheimer's disease assessment scale-cognitive subscale(ADAS-Cog)analysis with the results obtained on the same item in 4 trials with the cholinesterase inhibitor revealed a more positive trend with the cholinergic precursor choline alphoscerate than with this cholinesterase inhibitor.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase IV Trial for an Evaluation of the Efficacy of Gliatiline® on Post-stroke Patients With Vascular Cognitive Impairment no Dementia

Conditions
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Cognitive Impairment, Stroke

Intervention / Treatment
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* Drug: choline alfoscerate
* Drug: placebo (for choline alphoscerate)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients were outpatients (age 25 to 84 years) with vascular cognitive impairment that does not fulfill dementia criteria (vascular cognitive impairment, no dementia(CIND)), had been stroke free for 90 days, together with clinical and radiological evidence of stroke and can perform K-TMT-e A. Cognitive impairment did not meet the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia (ie, they did not have both memory impairment and other cognitive impairment that caused functional deficits). Exclusion Criteria: Exclusion criteria included clinical or radiological evidence of neurodegenerative disorders other than VCI. Patients with major depression or other psychiatric disorders (according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) were excluded. Patients who had experienced a myocardial infarction within 3 months of enrollment were excluded (although these patients could be reconsidered for inclusion once 3 months had elapsed), as were those with clinically relevant hepatic, pulmonary, gastrointestinal, or life-threatening disease. Additional reasons for exclusion included pregnancy, a history of alcohol or drug abuse, and contraindications for MRI studies. Medications that affect the cognitive function were not permitted within the last 30 days. Patients were not permitted to receive anticholinergic drugs or cholinergic agents other than gliatilin during the study period.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 84 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Choline alfoscerate<br>choline alfoscerate 400mg, 3 times a day, for 12 weeks. | Drug: choline alfoscerate<br>* Participants were randomly assigned to twice-daily doses of 400mg choline alphoscerate (alpha-glyceryl phosphoryl choline, Gliatilin®)<br>* Other names: Gliatilin®;|
| Placebo Comparator: placebo (for choline alfoscerate )<br>placebo tablet, 3 times a day, for 12 weeks. | Drug: placebo (for choline alphoscerate)<br>* Pill manufactured to mimic choline alfoscerate 400mg tablet<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of K-TMT-e A of K-VCIHS-NP in the choline alfoscerate vs the placebo groups. | Primary analysis compares the change of K-TMT-e A of K-VCIHS-NP from the study entry 12 weeks later in the choline alfoscerate vs the placebo groups. | 12 weeks after taking drugs | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the change of other determinants of K-VCIHS-NP in the choline alfoscerate vs the placebo groups | secondary analysis compares the change of other determinants of K-VCIHS-NP from the study entry 12 weeks later in the choline alfoscerate vs the placebo groups. | 12 weeks after taking drugs | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VCI-HS, stroke, choline alphoscerate