Rehabilitation Combined With Bihemispherictranscranial Direct Current Stimulation in Subacute Ischemic Stroke (RECOMBINE)

Rehabilitation Combined With Bihemispherictranscranial Direct Current Stimulation in Subacute Ischemic Stroke to Increase Upper Limb Motor Recovery, a Randomised, Controlled, Double-blind Study

Rehabilitation after stroke improves motor functions by promoting plastic changes however, after completing standard rehabilitation, 50-60% of patients still exhibit some degree of motor impairment and require at least partial assistance in activities of day living. Therefore, the exploration of other approaches to promote recovery is compulsory. Non invasive brain stimulation and motor rehabilitation are thought to share similar mechanisms in inducing neuroplastic changes in the human cortex and an emerging field of research is focusing on the possibility of coupling both therapies in order to achieve an additive effect and improve outcome.

We hypothesize that coupling bihemispheric transcranial direct current stimulation (tDCS) with simultaneous physical/occupational therapy in the subacute phase of ischemic stroke patients may improve upper limb motor recovery in humans.

This is a randomized, controlled, double blind, cross-over, multicentre, clinical trial. Thirty-six ischemic stroke patients in the subacute phase will be recruited in three centers of neurorehabilitation in Switzerland. After stratification based on the Fugl-Meyer Assessment Upper Extremity according to the severity of the deficit, the patient will be randomized to receive besides standardized physical/occupational treatment according to the Impairment-Oriented Training, tDCS of themotor cortex (1.5 mA, 30 minutes) (group 1: 12 patients) or sham stimulation (without current) (group 2: 12 patients). After three weeks of treatment group 1 and 2 will cross-over and will be treated for other three weeks. Group 3 (12 patients) will receive routine physical/occupational treatment and sham tDCS for six weeks. Assessment will be performed before starting tDCS, at week 3, 6 and at 6 months. Outcome measures are the Fugl-Meyer Assessment Upper Extremity, the extended Barthel Index, the Ashworth scale, the Test of Upper Limb Apraxia (only baseline, week 6, month6), the grip strength evaluated by the Jamar Hydraulic Hand dynamometer. At baseline at week 6 and at month 6 depression will be assessed by the Hamilton depression Rating Scale.

Study Overview

• Status: Unknown
• Conditions: Ischemic Stroke; First Ever Clinical Stroke; Subacute Phase; Persistent Hemiparesis of Upper Extremity
• Intervention / Treatment: Procedure: transcranial direct current stimulation (tDCS); Procedure: Sham stimulation, then tDCS; Procedure: Sham stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carlo Cereda, MD; Phone Number: +41 91 811 66 91; Email: Carlo.Cereda@eoc.ch
• Study Contact Backup: Name: Paolo Rossi, MD; Phone Number: +41 091 786 86 86; Email: paolo.rossi@clinica-hildebrand.ch

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Withdrawn
    • Universitätsspital Bern, Inselspital, Neuropsychologische Rehabilitation
  • Brissago, Switzerland, 6614
    • Recruiting
    • Clinica Hildebrand, Centro di riabilitazione Brissago
    • Contact: Paolo Rossi, MD; Phone Number: +41 91 786 86 86; Email: p.rossi@clinica-hildebrand.ch
    • Principal Investigator: Paolo Rossi, MD
  • Zihlschlacht, Switzerland, 8588
    • Terminated
    • HELIOS Klinik Zihlschlacht AG, Neurologisches Rehabilitationszentrum

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:

1. Ischemic lesions in the territory of middle cerebral artery subcortical or subcortical/cortical confirmed neuroimaging
2. Inclusion must be in the sub-acute phase defined as within 2-4 weeks after stroke
3. Persistent hemiparesis, indicated by a score of 1-3 on the motor arm item of the NIH Stroke Scale (NIHSS) (Brott et al. 1989) but wrist and finger movement is not required
4. No UE injury or conditions that limited use prior to the stroke.
5. The patient is >18 years old.
6. The patient has subscribed the informed consent

Exclusion Criteria:

1. History of epilepsy, brain tumor, major head trauma, learning disorder, severe cognitive impairment, drug or alcohol abuse, major psychiatric illness
2. Use of medications that may lower seizure threshold (e.g., metronidazole, fluoroquinolones)
3. Severe pain in the affected upper limb (>=8 on the shoulder item of the "joint pain during passive motion" of the Fugl-Meyer Assessment Upper Extremity)
4. Further stroke or other significant medical complication during the study
5. Evidence of severe leucoencephalopathy (grade IV according to the Fazeka's scale)
6. Important aphasia that would impair the understanding and performance of the assessment scales

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1 tDCS-Sham; tDC stimulation for 3 weeks, then cross-over to sham stimulation	Procedure: transcranial direct current stimulation (tDCS); Anodal tDCS of the ipsilesional motor cortex and cathodal tDCS of contralesional motor cortex (1.5 mA, 30 minutes) for 15 days during three weeks, then sham stimulation for 30 seconds on 15 days during 3 weeks
Experimental: 2 Sham-tDCS; Sham stimulation for 3 weeks, then cross over to tDCS stimulation	Procedure: Sham stimulation, then tDCS; Sham stimulation for 30 seconds on 15 days during 3 weeks, then anodal tDCS of the ipsilesional motor cortex and cathodal tDCS of contralesional motor cortex (1.5 mA, 30 minutes) for 15 days during three weeks
Sham Comparator: 3 Sham-Sham; Treatment for 6 weeks daily with sham stimulation	Procedure: Sham stimulation; Sham stimulation for 30 seconds on 15 days during 6 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl-Meyer Assessment Upper Extremity	Investigator administered questionnaire	6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl-Meyer Assessment Upper Extremity	Investigator administered questionnaire	3 weeks
Fugl-Meyer Assessment Upper Extremity	Investigator administered questionnaire	6 months
Barthel Index	Investigator administered questionnaire	3 weeks
Barthel Index	Investigator administered questionnaire	6 weeks
Barthel Index	Investigator administered questionnaire	6 months
Ashworth scale	Investigator administered questionnaire	3 weeks
Ashworth scale	Investigator administered questionnaire	6 weeks
Ashworth scale	Investigator administered questionnaire	6 months
Test of Upper Limb Apraxia (TULIA)	investigator administered questionnaire	6 weeks
Test of Upper Limb Apraxia (TULIA)	investigator administered questionnaire	6 months
Grip strength	Jamar Hydraulic Hand dynamometer	3 weeks
Grip strength	Jamar Hydraulic Hand dynamometer	6 weeks
Grip strength	Jamar Hydraulic Hand dynamometer	6 months
Hamilton depression Rating scale	Patient administered questionnaire	6 weeks
Hamilton depression Rating scale	Patient administered questionnaire	6 months

Collaborators and Investigators

• Sponsor: Dr. med. Carlo Cereda
• Collaborators: University Hospital Inselspital, Berne; CLINICA HILDEBRAND CENTRO DI RIABILITAZIONE BRISSAGO; Advisory Board Research Ente Ospedaliero Cantonale
• Investigators: Principal Investigator: Carlo Cereda, MD, Ospedale Regionale di Lugano - Civico

Publications and helpful links

General Publications

• Elsner B, Kugler J, Pohl M, Mehrholz J. Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke. Cochrane Database Syst Rev. 2020 Nov 11;11(11):CD009645. doi: 10.1002/14651858.CD009645.pub4.
• Lindenberg R, Renga V, Zhu LL, Nair D, Schlaug G. Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients. Neurology. 2010 Dec 14;75(24):2176-84. doi: 10.1212/WNL.0b013e318202013a. Epub 2010 Nov 10.

Helpful Links

• Link to the hospital coordinating the study
• Link to the hospital participating in the study
• Link to the clinic participating in the study

Study record dates

Study Major Dates

• Study Start: March 1, 2013
• Primary Completion (Anticipated): February 1, 2018
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: July 17, 2012
• First Submitted That Met QC Criteria: July 17, 2012
• First Posted (Estimate): July 19, 2012

Study Record Updates

• Last Update Posted (Actual): September 19, 2017
• Last Update Submitted That Met QC Criteria: September 18, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: rehabilitation; subacute; physiotherapy; ischemic stroke; hemiparesis; bihemispheric transcranial direct current stimulation; ergotherapy
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction; Paresis
• Other Study ID Numbers: EOC.NSI.11.02