Neurobiological Principles Applied to the Rehabilitation of Stroke Patients
12. října 2017 aktualizováno: 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.
Přehled studie
Postavení
Dokončeno
Podmínky
Detailní popis
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.
Typ studie
Intervenční
Zápis (Aktuální)
33
Fáze
- Nelze použít
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní místa
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Georgia
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Atlanta, Georgia, Spojené státy, 30322
- Emory University School of Medicine
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
18 let až 80 let (Dospělý, Starší dospělý)
Přijímá zdravé dobrovolníky
Ne
Pohlaví způsobilá ke studiu
Všechno
Popis
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
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Randomizované
- Intervenční model: Faktorové přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
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Experimentální: 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.
Ostatní jména:
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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Experimentální: 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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Experimentální: 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.
Ostatní jména:
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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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Aim 1: Mean Parameter Estimate for Maximal Motor Evoked Potential (MEPmax) Derived From Stimulus Response Curves (SRC)
Časové okno: 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
Časové okno: 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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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Aim 2: Mean Sum of Normalized Motor Evoked Potentials (MEPs) With Respect to Pulse
Časové okno: 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)
|
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Aim 2: Mean Peak Acceleration of Wrist Extension Movements With Respect to Pulse
Časové okno: Baseline, Post-Training 1(Immediately), Post-Training 2 (30 Minutes), Post-Training 3 (60 Minutes)
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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.
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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
Časové okno: 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)
|
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Aim 2: Mean Peak Acceleration for rTMS Treatment With Respect to Frequency
Časové okno: 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)
Časové okno: 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
Časové okno: 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)
|
Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Spolupracovníci
Vyšetřovatelé
- Vrchní vyšetřovatel: Cathrin M Buetefisch, MD, Emory University
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia
1. dubna 2007
Primární dokončení (Aktuální)
1. září 2016
Dokončení studie (Aktuální)
1. září 2016
Termíny zápisu do studia
První předloženo
11. července 2008
První předloženo, které splnilo kritéria kontroly kvality
11. července 2008
První zveřejněno (Odhad)
15. července 2008
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
16. října 2017
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
12. října 2017
Naposledy ověřeno
1. října 2017
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Kardiovaskulární choroby
- Cévní onemocnění
- Cerebrovaskulární poruchy
- Onemocnění mozku
- Onemocnění centrálního nervového systému
- Nemoci nervového systému
- Mrtvice
- Fyziologické účinky léků
- Adrenergní látky
- Neurotransmiterové látky
- Molekulární mechanismy farmakologického působení
- Autonomní agenti
- Agenti periferního nervového systému
- Inhibitory enzymů
- Imunologické faktory
- Inhibitory vychytávání neurotransmiterů
- Membránové transportní modulátory
- Agonisté dopaminu
- Dopaminové látky
- Adjuvans, Imunologická
- Inhibitory vychytávání dopaminu
- Stimulanty centrálního nervového systému
- Sympatomimetika
- Inhibitory adrenergního vychytávání
- Antiparkinsonoví agenti
- Činidla proti dyskinézi
- Inhibitory dekarboxylázy aromatických aminokyselin
- Methylfenidát
- Levodopa
- Amfetamin
- Carbidopa
- Karbidopa, kombinace léků levodopa
Další identifikační čísla studie
- IRB00046953
- R01NS060830-01A1 (Grant/smlouva NIH USA)
- NPARR01 (Jiný identifikátor: Other)
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .