Neuroregeneration Enhanced by Transcranial Direct Current Stimulation (TDCS) in Stroke

Stroke Clinical Trial

— NETS  

Official title:

Neuroregeneration Enhanced by TDCS in Stroke

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00909714
• Other study ID #: NETS Trial
• Status: Active, not recruiting
• Phase: N/A
• Start date: July 2009
• Est. completion date: September 30, 2021

Study information

• Verified date: May 2021
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Testing the hypothesis that non-invasive brain stimulation by transcranial direct current stimulation (tDCS) combined with functional training in the subacute phase of first-ever stroke will enhance functional regeneration compared with a Placebo intervention.

Description:

Stroke is the leading cause of long-term disability, which significantly impairs the economic and social life of patients and society. Every year 200 000 to 250 000 patients suffer a stroke in Germany. Only a small number of the stroke survivors recover to a degree that allows them to return into their professional and private life. Despite significant efforts to develop novel and efficient treatment strategies the level of functional regeneration is still not satisfying. Thus, the development of innovative and effective treatment strategies will have a major impact for the patients' life, the society and the public health system.

Within the proposed project an innovative, non-invasive and cost effective interventional strategy, based on the combination of a specific rehabilitative training and brain stimulation by transcranial direct current stimulation (tDCS), will be used to enhance functional regeneration in stroke patients. The intervention will be applied in an early stage in which plasticity, cortical reorganization and functional improvement is most pronounced. We hypothesize that the combination of anodal tDCS delivered to the motor cortex of the affected hemisphere combined with training over a period of two weeks in the subacute stage after stroke will significantly enhance cortical plasticity, functional regeneration and long-term outcome determined by clinical and functional outcome measures compared with Placebo stimulation.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 119
• Est. completion date: September 30, 2021
• Est. primary completion date: June 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Subacute stroke patients (5-45 days after stroke) with thromboembolic non-hemorrhagic subcortical or cortical, first clinically overt stroke will be included. Moderate to moderately severe upper-extremity hemiparesis, defined as an Upper Extremity Fugl-Meyer score (UEFMA) between 20 and 58 (inclusive).

Exclusion Criteria:

• pre-existing large lesions (> 1.5 cm maximum diameter) in a brain area that belongs to the anatomically established sensorimotor/premotor system

• progressive stroke

• completely lesioned hand knob area of M1 affected if no motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) are present

• bilateral motor impairment

• florid alcohol and/or drug abuse

• florid severe psychiatric illness (e.g. schizophrenia)

• severe language disturbances that prevents the patient to give informed consent or inhibit adequate scoring because of insufficient understanding of scoring introductions

• tumor diseases with a life expectancy less than one year

• increased intracranial pressure

• polyneuropathy and/or ischemic peripheral disease if the sensorimotor functions of the upper extremities are affected clinically relevant

• severe cognitive deficits (MMSE = 23)

• pregnancy

• contraindication for MRI or TMS

Related Conditions & MeSH terms

• Stroke

Intervention

Device:
• DC-Stimulator to apply tDCS
Anodal tDCS (20 minutes) stimulation will be applied once a day in combination with standardized upper extremity rehabilitative training
• DC-Stimulator to apply Sham tDCS
Sham stimulation will be applied once a day in combination with standardized upper extremity rehabilitative training

Locations

Country	Name	City	State
Austria	Neurologische Universitätsklinik Wien	Wien
Germany	Neurologische Klinik Bad Aibling	Bad Aibling
Germany	Neurologie Moritzklinik	Bad Klosterlausnitz	Thüringen
Germany	Neurologisches Zentrum Segeberger Kliniken	Bad Segeberg
Germany	NRZ Leipzig	Bennewitz
Germany	MEDIAN Klinik Berlin-Kladow	Berlin
Germany	Brandenburgklinik Berlin-Brandenburg	Bernau bei Berlin	Berlin
Germany	University Medical Center Hamburg Eppendorf (UKE)	Hamburg
Germany	University Medical Center Heidelberg	Heidelberg
Germany	Klinik Kipfenberg	Kipfenberg	Bayern
Italy	Fondazione Santa Lucia	Rome

Sponsors (1)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf

Countries where clinical trial is conducted

Austria,  Germany,  Italy, 

References & Publications (6)

Bikson M, Grossman P, Thomas C, Zannou AL, Jiang J, Adnan T, Mourdoukoutas AP, Kronberg G, Truong D, Boggio P, Brunoni AR, Charvet L, Fregni F, Fritsch B, Gillick B, Hamilton RH, Hampstead BM, Jankord R, Kirton A, Knotkova H, Liebetanz D, Liu A, Loo C, Nitsche MA, Reis J, Richardson JD, Rotenberg A, Turkeltaub PE, Woods AJ. Safety of Transcranial Direct Current Stimulation: Evidence Based Update 2016. Brain Stimul. 2016 Sep-Oct;9(5):641-661. doi: 10.1016/j.brs.2016.06.004. Epub 2016 Jun 15. Review. — View Citation

Bönstrup M, Krawinkel L, Schulz R, Cheng B, Feldheim J, Thomalla G, Cohen LG, Gerloff C. Low-Frequency Brain Oscillations Track Motor Recovery in Human Stroke. Ann Neurol. 2019 Dec;86(6):853-865. doi: 10.1002/ana.25615. Epub 2019 Oct 30. — View Citation

Bönstrup M, Schulz R, Schön G, Cheng B, Feldheim J, Thomalla G, Gerloff C. Parietofrontal network upregulation after motor stroke. Neuroimage Clin. 2018 Mar 7;18:720-729. doi: 10.1016/j.nicl.2018.03.006. eCollection 2018. — View Citation

Buch ER, Santarnecchi E, Antal A, Born J, Celnik PA, Classen J, Gerloff C, Hallett M, Hummel FC, Nitsche MA, Pascual-Leone A, Paulus WJ, Reis J, Robertson EM, Rothwell JC, Sandrini M, Schambra HM, Wassermann EM, Ziemann U, Cohen LG. Effects of tDCS on motor learning and memory formation: A consensus and critical position paper. Clin Neurophysiol. 2017 Apr;128(4):589-603. doi: 10.1016/j.clinph.2017.01.004. Epub 2017 Jan 29. Review. — View Citation

Pisegna JM, Kaneoka A, Pearson WG Jr, Kumar S, Langmore SE. Effects of non-invasive brain stimulation on post-stroke dysphagia: A systematic review and meta-analysis of randomized controlled trials. Clin Neurophysiol. 2016 Jan;127(1):956-968. doi: 10.1016/j.clinph.2015.04.069. Epub 2015 May 9. Review. — View Citation

Wessel MJ, Zimerman M, Timmermann JE, Heise KF, Gerloff C, Hummel FC. Enhancing Consolidation of a New Temporal Motor Skill by Cerebellar Noninvasive Stimulation. Cereb Cortex. 2016 Apr;26(4):1660-7. doi: 10.1093/cercor/bhu335. Epub 2015 Jan 20. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Upper Extremity Fugl-Meyer-Assessment (UEFMA)	standardized test of upper extremity function	1-7 days after the end of the intervention
Secondary	Upper Extremity Fugl-Meyer-Assessment (UEFMA)	standardized test of upper extremity function	30±10 days after the intervention
Secondary	Upper Extremity Fugl-Meyer-Assessment (UEFMA)	standardized test of upper extremity function	90±20 days after the intervention
Secondary	Upper Extremity Fugl-Meyer-Assessment (UEFMA) | Long-term outcome	standardized test of upper extremity function	12±1 months after the intervention
Secondary	Action Research Arm Test (ARAT)	standardized tests of upper extremity function	1-7 days after the end of the intervention
Secondary	Action Research Arm Test (ARAT)	standardized tests of upper extremity function	30±10 days after the intervention
Secondary	Action Research Arm Test (ARAT)	standardized tests of upper extremity function	90±20 days after the intervention
Secondary	Action Research Arm Test (ARAT) | Long-term outcome	standardized tests of upper extremity function	12±1 months after the intervention
Secondary	Nine Hole Peg Test (NHPT)	standardized test to assess fine motor skills	1-7 days after the end of the intervention
Secondary	Nine Hole Peg Test (NHPT)	standardized test to assess fine motor skills	30±10 days after the intervention
Secondary	Nine Hole Peg Test (NHPT)	standardized test to assess fine motor skills	90±20 days after the intervention
Secondary	Nine Hole Peg Test (NHPT) | Long-term outcome	standardized test to assess fine motor skills	12±1 months after the intervention
Secondary	Stroke Impact Scale (SIS)	questionnaire is to evaluate how stroke has impacted health and life of patients	1-7 days after the end of the intervention
Secondary	Stroke Impact Scale (SIS)	questionnaire is to evaluate how stroke has impacted health and life of patients	30±10 days after the intervention
Secondary	Stroke Impact Scale (SIS)	questionnaire is to evaluate how stroke has impacted health and life of patients	90±20 days after the intervention
Secondary	Stroke Impact Scale (SIS) | Long-term outcome	questionnaire is to evaluate how stroke has impacted health and life of patients	12±1 months after the intervention
Secondary	Box-and-Block Test	standardized test to assess fine motor skills	1-7 days after the end of the intervention
Secondary	Box-and-Block Test	standardized test to assess fine motor skills	30±10 days after the intervention
Secondary	Box-and-Block Test	standardized test to assess fine motor skills	90±20 days after the intervention
Secondary	Box-and-Block Test	standardized test to assess fine motor skills	12±1 months after the intervention
Secondary	Grip Force	dynamometer-based test to assess grip strength	1-7 days after the end of the intervention
Secondary	Grip Force	dynamometer-based test to assess grip strength	30±10 days after the intervention
Secondary	Grip Force	dynamometer-based test to assess grip strength	90±20 days after the intervention
Secondary	Grip Force	dynamometer-based test to assess grip strength	12±1 months after the intervention