Galantamine Treatment for Nonfluent Aphasia in Stroke Patients

Cognitive impairment after stroke is common and has a major effect on morbidity and quality of life. Acetylcholinesterase inhibitors have demonstrated benefit in vascular dementia, but efficacy in treating more circumscribed cognitive deficits following stroke, such as aphasia, has not been systematically investigated.

This study evaluated the efficacy of Galantamine (Reminyl) in subjects with chronic, stable non-fluent aphasia secondary to stroke. Subjects enrolled in a double-blind placebo- controlled cross-over study that employed a comprehensive battery of language tests and measures of general cognitive and behavioral status that will be used to control for factors that may influence language functioning. The primary study outcome was a within-subject comparison of changes in language function and behavioral scores between placebo and active-treatment phases (12 weeks each). Our hypothesis was that by increasing acetylcholine levels, and facilitating activity of other neurotransmitters affecting attentional systems, Galantamine would produce gains in both language and behavioral scores in patients suffering chronic effects in cognitive systems due to injury following stroke.

Study Overview

• Status: Completed
• Conditions: Stroke; Aphasia
• Intervention / Treatment: Drug: Galantamine; Drug: Placebo pill

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of aphasia with relatively spared comprehension.
• Onset 6 months or greater prior to enrollment.
• Native English speaker
• Right-handed.
• Adults (18 years of age or older).

Exclusion Criteria:

• Patients receiving ongoing individual speech therapy. (Most patients are no longer eligible for individualized speech therapy after 6 months from stroke onset, thus this should not eliminate many patients).
• Extremely mild or extremely severe aphasia. (Boston Naming Test Score <3 or >45 items named from 60 items).
• Global dementia (and any other patient with reduced decisional capacity requiring a legally authorized representative for consent).
• Presence of major cognitive deficit other than aphasia caused by stroke related disease.
• Contraindications to cholinomimetic agents: History of active peptic ulcer disease within 1 year, Severe asthma, unstable angina, bradyarrhythmia with resting pulse less than 50, sick sinus syndrome, or seizures.
• Major psychiatric disorders that affect cognition including: psychosis, major depression, bipolar disorder, alcohol or substance abuse.
• Major medical conditions that alter cognition (e.g., heart failure, dialysis dependent renal failure, hepatic failure, active cancer).
• Impairments that affect metabolism of the medication including: Severe renal impairment (Creatinine clearance equal to or greater than 9), and moderate or severe hepatic impairment (Child-Pugh score >7)
• Patients using medications that have major effects on brain neurotransmitter systems or cognition within 2 months of enrollment. Exclusionary medications are: medications with significant anti-cholinergic activity (tricyclic antidepressants, diphenhydramine), anti-Parkinsonian medications (including Sinemet, amantadine, bromocriptine, pergolide, selegiline), and narcotic analgesics (> 2 doses per week).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo pill; Placebo pill each morning with food for 12 weeks.
Active Comparator: Galantamine	Drug: Galantamine; Galantamine XL 8 mg for 4 weeks, followed by Galantamine XL 16 mg for subsequent 12 weeks. Taken in the morning with food for total of 12 weeks.; Other Names: Razadyne; Reminyl

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Spontaneous Speech	Analysis of spontaneous speech production with picture description (cookie theft picture): content units and lexical efficiency; as well as Boston Naming Test naming latency.	Every 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ADP	Aphasia Diagnostic Profile: lexical Retrieval, phrase length, phonemic fluency, and category fluency.	Every 4 weeks
Communication Log scores	Subject communication change log scores Caregiver communication change log score	Every 12 weeks

Collaborators and Investigators

• Sponsor: University of North Carolina, Chapel Hill
• Collaborators: Ortho-McNeil Neurologics, Inc.
• Investigators: Principal Investigator: Heidi L Roth, MD, University of North Carolina

Study record dates

Study Major Dates

• Study Start: October 1, 2004
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: May 21, 2010
• First Submitted That Met QC Criteria: May 21, 2010
• First Posted (Estimate): May 24, 2010

Study Record Updates

• Last Update Posted (Estimate): May 24, 2010
• Last Update Submitted That Met QC Criteria: May 21, 2010
• Last Verified: May 1, 2010

More Information

Terms related to this study

• Keywords: treatment; stroke; Aphasia; cholinesterase inhibitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Language Disorders; Communication Disorders; Speech Disorders; Stroke; Aphasia; Aphasia, Broca; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Parasympathomimetics; Galantamine
• Other Study ID Numbers: GAL-EMR-4008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No