Dopaminergic Enhancement of Learning and Memory in Aphasia

Dopaminergic Enhancement of Learning and Memory (LL_001, Project on Aphasia)

The purpose of this study is to determine whether levodopa, in combination with a high frequency language training, is effective in boosting naming performance in patients with aphasia.

Study Overview

• Status: Completed
• Conditions: Aphasia; Cerebrovascular Accident
• Intervention / Treatment: Drug: levodopa

Detailed Description

Our prior work shows that d-amphetamine and the dopamine precursor levodopa markedly improve word learning success in healthy subjects. In this randomized, placebo-controlled, double-blind clinical trial, we probe whether daily administration of levodopa, coupled with several hours of language training every day, will significantly improve naming abilities in patients with aphasia as compared to placebo administration. We furthermore examine with magnetic resonance imaging which brain regions need to be functionally intact for a dopaminergic improvement of language therapy.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Muenster, Nordrhein-Westfalen, Germany, 48129
      • Dept. of Neurology, University Hospital Muenster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria for patients with aphasia:

• Unilateral cerebrovascular accident (stroke) in the territory of the arteria media
• Time post onset: > 6 months
• Aphasia with anomia
• Age between 18-75 years
• Premorbid right-handedness
• Primary language: German

Exclusion Criteria for patients and healthy controls:

• Known allergy to levodopa or tartrazine
• History of medication/drug abuse
• Acute nicotine withdrawal or > 15 cigarettes per day
• > 6 cups/glasses of coffee, caffeine drinks or energy drinks per day
• > 50 grams of alcohol per day
• Severe hypertonia (systole >180 mm Hg)
• Severe arteriosclerosis
• Diabetes, asthma, or glaucoma
• Severe hearing disability
• Evidence for severe hippocampal damage
• Premorbid depression or psychosis
• Medication with dopamine agonists or antagonists
• Parkinsonian symptoms
• Changes in anticonvulsive medication during the week prior to study enrollment

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Boost in naming performance (percent correct) through levodopa as compared to placebo	immediately after each treatmentphase
Brain activity pattern in successfully trained patients	immediately after each treatmentphase

Secondary Outcome Measures

Outcome Measure	Time Frame
Stability of naming performance after one month and six months post treatment	from 1 month untill 6 months after treatment completion

Collaborators and Investigators

• Sponsor: University Hospital Muenster
• Collaborators: German Federal Ministry of Education and Research
• Investigators: Study Director: Caterina Breitenstein, PhD, Dept. of Neurology, University Hospital Muenster, Germany; Study Chair: Stefan Knecht, MD, Dept. of Neurology, University Hospital Muenster, Germany

Publications and helpful links

General Publications

• Knecht S, Breitenstein C, Bushuven S, Wailke S, Kamping S, Floel A, Zwitserlood P, Ringelstein EB. Levodopa: faster and better word learning in normal humans. Ann Neurol. 2004 Jul;56(1):20-6. doi: 10.1002/ana.20125.
• Breitenstein C, Knecht S. [Language acquisition and statistical learning]. Nervenarzt. 2003 Feb;74(2):133-43. doi: 10.1007/s00115-002-1466-1. German.
• Breitenstein C, Wailke S, Bushuven S, Kamping S, Zwitserlood P, Ringelstein EB, Knecht S. D-amphetamine boosts language learning independent of its cardiovascular and motor arousing effects. Neuropsychopharmacology. 2004 Sep;29(9):1704-14. doi: 10.1038/sj.npp.1300464.
• Breitenstein C, Korsukewitz C, Baumgartner A, Floel A, Zwitserlood P, Dobel C, Knecht S. L-dopa does not add to the success of high-intensity language training in aphasia. Restor Neurol Neurosci. 2015;33(2):115-20. doi: 10.3233/RNN-140435.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): February 1, 2007
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 3, 2005
• First Submitted That Met QC Criteria: February 3, 2005
• First Posted (Estimate): February 4, 2005

Study Record Updates

• Last Update Posted (Estimate): October 7, 2013
• Last Update Submitted That Met QC Criteria: October 4, 2013
• Last Verified: June 1, 2008

More Information

Terms related to this study

• Keywords: stroke; levodopa; stroke recovery; plasticity; language acquisition; naming; aphasia treatment
• 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; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Antiparkinson Agents; Anti-Dyskinesia Agents; Levodopa
• Other Study ID Numbers: LL_001, Project on aphasia