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

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

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).

Study Overview

• Status: Completed
• Conditions: Stroke; Cognitive Impairment
• Intervention / Treatment: Drug: choline alfoscerate; Drug: placebo (for choline alphoscerate)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 222
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gyeoinggido
    • Seongnam, Gyeoinggido, Korea, Republic of, 463-707
      • Seoul National University Bundang

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Investigators: Principal Investigator: Hee-JOON BAE, Proffessor, Seoul National University Bundang Hospital

Publications and helpful links

General Publications

• Parnetti L, Mignini F, Tomassoni D, Traini E, Amenta F. Cholinergic precursors in the treatment of cognitive impairment of vascular origin: ineffective approaches or need for re-evaluation? J Neurol Sci. 2007 Jun 15;257(1-2):264-9. doi: 10.1016/j.jns.2007.01.043. Epub 2007 Feb 28.

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: May 29, 2011
• First Submitted That Met QC Criteria: May 31, 2011
• First Posted (Estimate): June 1, 2011

Study Record Updates

• Last Update Posted (Estimate): October 14, 2013
• Last Update Submitted That Met QC Criteria: October 11, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Keywords: stroke; VCI-HS; choline alphoscerate
• Additional Relevant MeSH Terms: Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Cognition Disorders; Stroke; Dementia; Cognitive Dysfunction; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gastrointestinal Agents; Hypolipidemic Agents; Lipid Regulating Agents; Nootropic Agents; Lipotropic Agents; Choline
• Other Study ID Numbers: GLITTER-DW400; MOON KU HAN (Registry Identifier: GLITTER)