Neurobiological Principles Applied to the Rehabilitation of Stroke Patients

NCT00715520 | Completed Results

• 3 other identifiers: IRB00046953R01NS060830-01A1NPARR01
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to use (Transcranial Magnetic Stimulation) TMS or drugs to improve learning of movement skills and the adaptation processes in patients after stroke. Once investigators have determined the improving effect of TMS and the drugs on learning of movement skills, the study team may be able to provide information that improves rehabilitative treatment and helps to improve recovery after stroke.

Conditions

Stroke

Keywords

Transcranial Magnetic Stimulation; Rehabilitation; Stroke; Plasticity

Outcome Measures

Primary Outcomes (2)

• Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)

  Motor evoked potential (MEP) amplitudes were measured prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2), and 60 minutes after the treatment (post-training 3).The MEP is elicited by transcranial magnetic stimulation (TMS) at increased intensity. Its amplitude is measured from peak to peak and expressed in millivolts (mV). Measured MEP amplitudes were plotted against the intensity to create a stimulus response curve (SRC). SRCs were modeled by a 3- parameter sigmoid function and MEPmax was extracted. Long-lasting increases in MEP amplitude indicate increases in motor cortex excitability and are associated with motor learning.

  Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

• Aim 1: Mean Peak Acceleration of Wrist Extension Movements

  Mean peak acceleration was measured across study drug conditions prior to treatment (baseline), immediately after the treatment (post-training 1), 30 minutes after the treatment (post-training 2) and 60 minutes after the treatment (post-training 3). Increases in the mean peak acceleration of the trained wrist extension movements indicate motor learning. Acceleration was measured in g; a symbol for the average acceleration produced by gravity at the Earth's surface.

  Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

Secondary Outcomes (6)

• Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) With Respect to Pulse

  Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

• Aim 2: Mean Peak Acceleration of Wrist Extension Movements With Respect to Pulse

  Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

• Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) for rTMS Treatment With Respect to Frequency

  Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

• Aim 2: Mean Peak Acceleration for rTMS Treatment With Respect to Frequency

  Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

• Aim 3: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)

  Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)

Study Arms (3)

Aim 1

EXPERIMENTAL

Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.

Drug: Carbidopa-Levodopa; Drug: Methylphenidate; Drug: Amphetamine Sulfate; Drug: Placebo; Other: Transcranial Magnetic Stimulation (TMS) Training

Aim 2

EXPERIMENTAL

Healthy adult female and male subjects will receive repetitive TMS (rTMS) at different times or frequencies with respect to the training movement or sham stimulation.

Other: Transcranial Magnetic Stimulation (TMS); Other: Sham Transcranial Magnetic Stimulation (TMS)

Aim 3

EXPERIMENTAL

Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.

Drug: Carbidopa-Levodopa; Drug: Methylphenidate; Drug: Amphetamine Sulfate; Drug: Placebo; Other: Sham Transcranial Magnetic Stimulation (TMS); Other: Transcranial Magnetic Stimulation (TMS) Training

Interventions

Transcranial Magnetic Stimulation (TMS) OTHER

Each TMS training session will begin with a baseline measurement lasting about 30 minutes in which brief magnetic pulses will be generated by the single-pulse and paired pulse TMS stimulator and the responses are recorded with surface EMG electrodes. Participants will be instructed to move their wrist for up to ½ hour. After these measures, rTMS will be applied to the scalp during training. Stimulation will occur at a low rate of different frequencies and different times with respect to the training movement depending on the experimental condition. In the last phase of the session post-training measurements will be done using single TMS pulses. TMS pulses and intensity with be given in random order.

Aim 2

Carbidopa-Levodopa DRUG

Participants will receive one oral dose of carbidopa-levodopa 25mg one hour prior to measuring wrist extension movements. The order in which Carbidopa-Levodopa is given will be randomized per participant.

Also known as: Sinemet

Aim 1; Aim 3

Methylphenidate DRUG

Participants will receive one oral dose of methylphenidate 40mg 2 hours prior to measuring wrist extension movements. The order in which Methylphenidate is given will be randomized per participant.

Aim 1; Aim 3

Amphetamine Sulfate DRUG

Participants will receive one oral dose of amphetamine sulfate 10mg 2 hours prior to measuring wrist extension movements. The order in which Amphetamine Sulfate is given will be randomized per participant.

Aim 1; Aim 3

Placebo DRUG

Participants will receive one oral tablet of placebo 2 hours prior to measuring wrist extension movements. The order in which Placebo is given will be randomized per participant.

Aim 1; Aim 3

Sham Transcranial Magnetic Stimulation (TMS) OTHER

Sham TMS pulses will be randomly administered during TMS sessions.

Aim 2; Aim 3

Transcranial Magnetic Stimulation (TMS) Training OTHER

TMS surface electromyographic activity will be recorded with surface electrodes mounted on the skin overlaying a forearm muscle. Single pulses of TMS at increasing intensity will be delivered to measure motor cortex excitability. Peak acceleration and TMS evoked responses in the muscle will be measured prior to the training, after completion of the training and again one hour after completion of the training.

Aim 1; Aim 3

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Normal neurological examination
• Ability to give informed consent.

You may not qualify if:

• History or neurological or psychiatric disease
• Abnormal MRI of brain
• Abnormal neuropsychological testing
• Intake of CNS active drugs
• History of seizure disorder
• History of migraine headaches
• History of anaphylaxis or allergic reactions
• Contraindication to TMS
• Aim 3:
• Cerebral ischemic infarction more than 6 months prior to entering the study
• Single lesion as defined by MRI of the brain affecting the primary motor output system of the hand at a cortical (M1) level or subcortical level, or unilateral, and supratentorial in absence of history of a previous symptomatic stroke within 3 months of the current stroke
• Dense paresis of the hand for more than three days after cerebral infarction (MRC of \< 4- of wrist- and finger extension/flexion movements)
• Good functional recovery of hand function as defined by MRC of 4 or 4+ of wrist- and finger extension/flexion movements
• Ability to perform wrist extension movements
• Ability to give informed consent

Sponsors & Collaborators

• Emory University: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Magnetic Stimulation; carbidopa, levodopa drug combination; Methylphenidate; Amphetamine

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amphetamines; Phenethylamines; Ethylamines; Amines

Limitations and Caveats

Target enrollment for aim 3 was not me due to difficulty identifying participants that met the inclusion criteria. Therefore the study team did not have a sufficient sample size to complete any data analysis for this aim.

Results Point of Contact

• Title: Dr. Cathrin Buetefisch
• Organization: Emory University

cathrin.buetefisch@emory.edu

4047121894

Study Officials

• Cathrin M Buetefisch, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr. Cathrin Buetefisch

Study Record Dates

• First Submitted: July 11, 2008
• First Posted: July 15, 2008
• Study Start: April 1, 2007
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: October 16, 2017
• Results First Posted: October 16, 2017

Record last verified: 2017-10

Locations

US (1)