Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
12 de outubro de 2017 atualizado por: Cathrin Buetefisch, Emory University
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.
Visão geral do estudo
Status
Concluído
Condições
Descrição detalhada
Previous studies have shown, that when patients learn a new motor movement, it may cause a change in the way the nerves act in the area of the brain that controls movement.
This change is called use-dependent plasticity.
The ability of that part of the brain, called the motor cortex (M1), to reorganize plays a major role in the recovery of motor deficits post-stroke; hence the importance for further development of rehabilitative strategies that utilize this potential for recovery.
In this proposed study, investigators will further examine influences of use-dependent plasticity in the non-injured M1 of healthy subjects and injured M1 of stroke subjects using a combination of non-invasive cortical stimulation, medication, and exercise techniques.
In Aim 1, investigators will test the effect of drugs that interact specifically with different neurotransmitter systems on use-dependent plasticity in intact M1 of healthy humans.
In Aim 2, investigators will identify the parameters for non-invasive transcranial magnetic stimulation (TMS) of M1 that are most effective to enhance use-dependent plasticity in intact healthy human M1.
In Aim 3, investigators will test the drugs and rTMS protocols that were demonstrated to be most effective to enhance use- dependent plasticity in the Specific Aim 1 and 2 and apply them to participants who have experienced a stroke.
Results from this study will help to inform future research about the efficacy of plasticity enhancing methods in injured M1 of stroke patients.
Tipo de estudo
Intervencional
Inscrição (Real)
33
Estágio
- Não aplicável
Contactos e Locais
Esta seção fornece os detalhes de contato para aqueles que conduzem o estudo e informações sobre onde este estudo está sendo realizado.
Locais de estudo
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Georgia
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Atlanta, Georgia, Estados Unidos, 30322
- Emory University School of Medicine
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Critérios de participação
Os pesquisadores procuram pessoas que se encaixem em uma determinada descrição, chamada de critérios de elegibilidade. Alguns exemplos desses critérios são a condição geral de saúde de uma pessoa ou tratamentos anteriores.
Critérios de elegibilidade
Idades elegíveis para estudo
18 anos a 80 anos (Adulto, Adulto mais velho)
Aceita Voluntários Saudáveis
Não
Gêneros Elegíveis para o Estudo
Tudo
Descrição
Aims 1 and 2
Inclusion Criteria:
- Normal neurological examination
- Ability to meet criteria of inclusion experiment
- Ability to give informed consent.
Exclusion Criteria:
- 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:
Inclusion Criteria:
- 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 meet criteria of inclusion experiment
- Ability to give informed consent
- Ability of TMS to elicit a measurable MEP of > 100 μV and an increase in MEP amplitude with increasing stimulus intensity (up to 100% of MSO) of at least 20% over MEP amplitude at MT
Exclusion Criteria:
- History or neurological or psychiatric disease, including bipolar disorder
- Intake of CNS active drugs
- History of seizure disorder
- History of migraine headaches
- History of anaphylaxis or allergic reactions
- Contraindication to TMS
Plano de estudo
Esta seção fornece detalhes do plano de estudo, incluindo como o estudo é projetado e o que o estudo está medindo.
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição fatorial
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
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Experimental: Aim 1
Healthy adult female and male subjects will receive study drugs and TMS training to measure M1 excitability.
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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.
Outros nomes:
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. 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. 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.
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.
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Experimental: Aim 2
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.
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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.
Sham TMS pulses will be randomly administered during TMS sessions.
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Experimental: Aim 3
Female and male subjects who have experienced a cerebral ischemic infarction, will receive study drugs and TMS to measure M1 excitability.
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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.
Outros nomes:
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. 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. 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.
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.
Sham TMS pulses will be randomly administered during TMS sessions.
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Prazo: Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
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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.
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Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
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Aim 1: Mean Peak Acceleration of Wrist Extension Movements
Prazo: Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
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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.
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Baseline, Post-Training 1 (Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
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Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) With Respect to Pulse
Prazo: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
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Mean sum of normalized MEP for repeated TMS (rTMS) conditions with respect to the pulse (-100, +300, placebo, zero) 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).
Its amplitude is measured from peak to peak and expressed in mV.
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 2: Mean Peak Acceleration of Wrist Extension Movements With Respect to Pulse
Prazo: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
|
Mean peak acceleration of wrist movements for repeated TMS (rTMS) conditions with respect of the TMS pulse (-100, +300, placebo, zero) 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)
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Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) for rTMS Treatment With Respect to Frequency
Prazo: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
|
Mean sum of normalized MEP for the different frequencies of rTMS treatment (placebo at 0.1 Hz, 0.1 Hz, 0.25 Hz, 0.5 Hz) 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.
|
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
Prazo: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
|
Mean peak acceleration for the different frequencies of rTMS treatment (placebo, 0.1 Hz, 0.25 Hz, 0.5 Hz) 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)
|
|
Aim 3: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Prazo: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
|
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 3: Mean Peak Acceleration of Wrist Extension Movements
Prazo: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
|
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)
|
Colaboradores e Investigadores
É aqui que você encontrará pessoas e organizações envolvidas com este estudo.
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Cathrin M Buetefisch, MD, Emory University
Datas de registro do estudo
Essas datas acompanham o progresso do registro do estudo e os envios de resumo dos resultados para ClinicalTrials.gov. Os registros do estudo e os resultados relatados são revisados pela National Library of Medicine (NLM) para garantir que atendam aos padrões específicos de controle de qualidade antes de serem publicados no site público.
Datas Principais do Estudo
Início do estudo
1 de abril de 2007
Conclusão Primária (Real)
1 de setembro de 2016
Conclusão do estudo (Real)
1 de setembro de 2016
Datas de inscrição no estudo
Enviado pela primeira vez
11 de julho de 2008
Enviado pela primeira vez que atendeu aos critérios de CQ
11 de julho de 2008
Primeira postagem (Estimativa)
15 de julho de 2008
Atualizações de registro de estudo
Última Atualização Postada (Real)
16 de outubro de 2017
Última atualização enviada que atendeu aos critérios de controle de qualidade
12 de outubro de 2017
Última verificação
1 de outubro de 2017
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças cardiovasculares
- Doenças Vasculares
- Distúrbios Cerebrovasculares
- Doenças Cerebrais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Derrame
- Efeitos Fisiológicos das Drogas
- Agentes Adrenérgicos
- Agentes Neurotransmissores
- Mecanismos Moleculares de Ação Farmacológica
- Agentes Autônomos
- Agentes do Sistema Nervoso Periférico
- Inibidores Enzimáticos
- Fatores imunológicos
- Inibidores de Captação de Neurotransmissores
- Moduladores de transporte de membrana
- Agonistas de Dopamina
- Agentes de Dopamina
- Adjuvantes Imunológicos
- Inibidores de Captação de Dopamina
- Estimulantes do Sistema Nervoso Central
- Simpaticomiméticos
- Inibidores da Captação Adrenérgica
- Agentes antiparkinsonianos
- Agentes Antidiscinesia
- Inibidores da Descarboxilase de Aminoácidos Aromáticos
- Metilfenidato
- Levodopa
- Anfetamina
- Carbidopa
- Carbidopa, combinação de drogas levodopa
Outros números de identificação do estudo
- IRB00046953
- R01NS060830-01A1 (Concessão/Contrato do NIH dos EUA)
- NPARR01 (Outro identificador: Other)
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .