Dextroamphetamine and tDCS to Improve the Fluency

Transcranial Direct Current Stimulation and Melodic Intonation Therapy Combined With Dextroamphetamine in Chronic Stroke Patients With Non-fluent Aphasia; Safety and Efficacy Phase

The proposed study aims to evaluate safety and efficacy of combined dextroamphetamine (Dexedrine) and transcranial direct current stimulation (tDCS) with melodic intonation therapy (MIT) for treatment of aphasia after stroke. The target population is patients with chronic speech deficits due to a left hemisphere non-hemorrhagic stroke. Findings from this proposed project will help in the design of future larger studies.The safety phase will use cross-over, placebo controlled and single-blinded design. 10 participants with post stroke chronic non-fluent aphasia will undergo two experiments. To study the safety and effect of combined dextroamphetamine, tDCS and MIT therapy the study will use a parallel-groups, randomized, sham and placebo controlled, and double-blinded design in which 48 participants with post stroke chronic non-fluent aphasia will be randomly assigned to receive either 1) dextroamphetamine therapy with active stimulation, 2) placebo medication with active stimulation, 3) dextroamphetamine therapy with sham stimulation or 4) placebo medication with sham stimulation for the same duration.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Placebo; Drug: Dexedrine; Behavioral: Speech Therapy; Device: Sham tDCS; Device: Active tDCS

Detailed Description

Two phases were planned for this study, as described below. The safety phase of the study was completed; however, due to limited funding, the efficacy phase was never started (that is, the efficacy phase was terminated).

SAFETY PHASE: The safety phase will use cross-over, placebo controlled and single-blinded design. 10 participants with post stroke chronic non-fluent aphasia will undergo two experiments. In the experiment 1, the subjects will receive 10 mg dextroamphetamine, 1.5 mA anodal tDCS to right inferior frontal gyrus (right Broca's area), and melodic intonation therapy. The two experiments of one time intervention will be separated by 1 week of washout and when the subjects come back for experiment 2, any later side effects will be evaluated. In the experiment 2, the subjects will receive placebo medication with anodal tDCS to right IFG (Broca's area) and melodic intonation therapy. During the experiments, thirty minutes before stimulation, participants in the active drug experiment (n=10) will take 10 mg dextroamphetamine per oral -experiment 1- and participants in the placebo drug experiment will take placebo pill per oral -experiment 2-. During the 20 minute stimulation phase, the participants (n=10) will receive anodal tDCS (1.5 mA) on ipsilesional right inferior frontal gyrus (Broca's area). All participants will simultaneously receive melodic intonation therapy for duration of an hour during and after 20 minutes of stimulation.

EFFICACY PHASE: To study the safety and effect of combined dextroamphetamine, tDCS and MIT therapy the study will use a parallel-groups, randomized, sham and placebo controlled, and double-blinded design in which 48 participants with post stroke chronic non-fluent aphasia will be randomly assigned to receive either 1) dextroamphetamine therapy with active stimulation, 2) placebo medication with active stimulation, 3) dextroamphetamine therapy with sham stimulation or 4) placebo medication with sham stimulation for the same duration. The subjects from the previous step of the study will be asked to participate to this step. Thirty minutes before stimulation participants in the active drug groups, group 1 (n=12) and group 3 (n=12) will take dextroamphetamine 10 mg per oral and participants in the placebo groups, group 2 (n=12) and group 4 (n=12) will take placebo pill per oral. During the 20 minute stimulation phase, the participants in the active stimulation groups, groups 1 (n=12) and 2 (n=12) will receive anodal tDCS (1.5 mA) on right inferior frontal gyrus (Broca's area), and participants in the sham control groups, group 3 (n=12) and group 4 (n=12) will receive sham stimulation. All participants will simultaneously receive melodic intonation therapy for duration of an hour during and after 20 minutes of stimulation. Treatment will be administered at an intensity of 5 sessions per week for 2 weeks.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center

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:

• Age above 18
• Native English proficiency;
• Nonfluent speech;
• Premorbid right handedness;
• Non-hemorrhagic left hemispheric stroke at least 6 months prior to the investigation.
• No contraindications for MRI (only subjects who will undergo MRI scan).

Exclusion Criteria:

• Hypersensitivity or idiosyncrasy to dextroamphetamine or to other sympathomimetic agents;
• Pregnant or trying to become pregnant;
• Active alcohol abuse, illicit drug use or drug abuse or significant mental illness;
• Subjects receiving alpha adrenergic antagonists or agonists;
• Any history of epilepsy;
• Any condition that would prevent the subject from giving voluntary informed consent;
• An implanted brain stimulator;
• Aneurysm clip or other metal in the brain;
• Enrolled or plans to enroll in an interventional trial during this study;
• Scalp wounds or infections;
• Previous stroke with residual deficits (TIAs not a reason for exclusion);
• A concurrent progressive neurologic disorder, acute coronary syndrome, severe heart disease (NYHA Classification > 3), or other major medical condition;
• Advanced atherosclerosis, Unstable cardiac dysrhythmia or uncontrolled hypertension (>160/100 mm Hg), or untreated hyperthyroidism;
• Diagnosis of glaucoma
• During or within 14 days following the administration of monoamine oxidase inhibitors;
• Subjects requiring palliative care;
• Terminal medical condition such as AIDS or cancer;
• Subjects unable to comprehend or follow verbal commands;
• Based on PI's or local physician's assessment patient unable to tolerate the trial procedure due to medical condition;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Dexedrine+sham tDCS+speech therapy; 10 mg Dexedrine and speech therapy for 10 days	Drug: Dexedrine; 10 mg immediate release of Dexedrine; Other Names: Adderall, Dexedrine; Behavioral: Speech Therapy; 60 min of speech therapy; Other Names: Melodic Intonation Therapy; Device: Sham tDCS
EXPERIMENTAL: active tDCS+placebo+speech therapy; 1.5 mA anodal tDCS and speech therapy for 10 days	Drug: Placebo; Behavioral: Speech Therapy; 60 min of speech therapy; Other Names: Melodic Intonation Therapy; Device: Active tDCS; 1.5 mA tDCS anodal tDCS
EXPERIMENTAL: Dexedrine+tDCS+speech therapy; 10 mg Dexedrine, 1.5 mA anodal tDCS, and speech therapy for 10 days	Drug: Dexedrine; 10 mg immediate release of Dexedrine; Other Names: Adderall, Dexedrine; Behavioral: Speech Therapy; 60 min of speech therapy; Other Names: Melodic Intonation Therapy; Device: Active tDCS; 1.5 mA tDCS anodal tDCS
EXPERIMENTAL: sham stimulation+placebo+speech therapy; Sham stimulation, placebo and speech therapy for 10 days	Drug: Placebo; Behavioral: Speech Therapy; 60 min of speech therapy; Other Names: Melodic Intonation Therapy; Device: Sham tDCS
EXPERIMENTAL: Dexedrine+tDCS+Speech Therapy; 10 mg Dexedrine, 1.5 mA anodal tDCS, and speech therapy for 1 day	Drug: Dexedrine; 10 mg immediate release of Dexedrine; Other Names: Adderall, Dexedrine; Behavioral: Speech Therapy; 60 min of speech therapy; Other Names: Melodic Intonation Therapy; Device: Active tDCS; 1.5 mA tDCS anodal tDCS
EXPERIMENTAL: placebo+tDCS+Speech Therapy; 1.5 mA anodal tDCS, and speech therapy for 1 day	Drug: Placebo; Behavioral: Speech Therapy; 60 min of speech therapy; Other Names: Melodic Intonation Therapy; Device: Active tDCS; 1.5 mA tDCS anodal tDCS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Language Quotient as Assessed by the Western Aphasia Battery	The score on the Language Quotient of the Western Aphasia Battery ranges between 0-100. Higher scores indicate better performance. Below, percent change in the score is reported.	immediately before the treatment, immediately after the treatment
Percent Change in Aphasia Quotient as Assessed by the Western Aphasia Battery	The score on the Aphasia Quotient of the Western Aphasia Battery ranges between 0-100. Higher scores indicate better performance. Below, percent change in the score is reported.	immediately before the treatment, immediately after the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Boston Diagnostic Aphasia Examination		Baseline,2 weeks
Boston Diagnostic Aphasia Examination		Baseline,2 months
Percent Change in Blood Pressure	Non-invasive BP measurements performed by a clinician before and after each experiment.	immediately before the treatment, after after the treatment

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Investigators: Principal Investigator: Gerard E Francisco, MD, University of Texas Health Science Center at Houston, Department of Physical Medicine and Rehabilitation

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (ACTUAL): December 1, 2015
• Study Completion (ACTUAL): December 1, 2015

Study Registration Dates

• First Submitted: June 4, 2015
• First Submitted That Met QC Criteria: July 30, 2015
• First Posted (ESTIMATE): August 3, 2015

Study Record Updates

• Last Update Posted (ACTUAL): August 3, 2018
• Last Update Submitted That Met QC Criteria: July 3, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Dopamine Agents; Dopamine Uptake Inhibitors; Central Nervous System Stimulants; Dextroamphetamine; Adderall
• Other Study ID Numbers: HSC-MS-14-0354