NCT02020421

Brief Summary

The current standard of care for rehabilitation of patients with aphasia after stroke is conventional speech and language therapy (SLT). Due to economic realities on most stroke units, SLT can often not be given with optimal intensity in the first weeks after the stroke. Developing new adjuvant therapies which may render SLT sessions more effective is thus one approach to improve rehabilitation outcome. Recent functional imaging studies in post-stroke aphasia have shown that the recruitment of brain regions in the unaffected hemisphere seems to be an inferior strategy for recovery of language function as compared to re-activation of brain regions in the vicinity of the infarct. Non-invasive brain stimulation techniques, such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) are new methods to modulate brain activity. Evidence from our own feasibility study in sub-acute stroke suggests that these new techniques, when applied in conjunction with conventional SLT, may help to normalize brain activation patterns and might yield better rehabilitation outcome than SLT alone. With NORTHSTAR, we propose a multicenter proof-of-concept study to investigate the safety, feasibility and efficacy of these new non-invasive brain stimulation methods as adjuvant therapies for subacute post-stroke aphasia. Our goal is to determine the most effective brain stimulation modality to decrease inhibition onto the left side of the brain. We will assess if a combination of brain stimulation and speech and language therapy will improve language recovery. We will quantify language recovery (expressive and comprehensive skills) using specific tests, commonly used by speech and language therapists. We will invite patients recently admitted to the stroke unit of the study centers to participate in our research project. Once patients consent to our study we will randomly assign them to one of three experimental groups. For 12 days, all groups of patients will be setup with brain stimulation during their usual rehabilitation sessions. Two of those groups (treatment groups) will each receive a different type of brain stimulation (rTMS and tDCS), in the third group, patients will not receive real stimulation (placebo group). By comparing the extent of aphasia recovery between groups, we will determine the benefits attributable to brain stimulation relative to SLT alone.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
63

participants targeted

Target at P50-P75 for not_applicable

Timeline
Completed

Started Dec 2013

Longer than P75 for not_applicable

Geographic Reach
3 countries

6 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

December 1, 2013

Completed
9 days until next milestone

First Submitted

Initial submission to the registry

December 10, 2013

Completed
14 days until next milestone

First Posted

Study publicly available on registry

December 24, 2013

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2018

Completed
Last Updated

October 26, 2021

Status Verified

October 1, 2021

Enrollment Period

4.2 years

First QC Date

December 10, 2013

Last Update Submit

October 18, 2021

Conditions

Keywords

ischemic strokerehabilitationaphasianon-invasive brain stimulation

Outcome Measures

Primary Outcomes (5)

  • Change from baseline in verbal fluency on the Verbal fluency test at 1 and 30 days after completion of the treatment period

    Verbal fluency test

    at baseline, 1 and 30 days after completion of the treatment period

  • Change from baseline in language comprehension on the Token test at 1 and 30 days after completion of the treatment period

    Token test

    at baseline, 1 and 30 days after completion of the treatment period

  • Cumulative number of Adverse Events and Serious Adverse Events during 10 days of therapy

    Cumulative number of Adverse Effects and Serious Adverse Effects during 10 days of therapy

    at each days of treatment

  • Change from baseline in naming ability on the Boston naming test at 1 and 30 days after completion of the treatment period

    Boston Naming Test

    at baseline, 1 and 30 days after completion of the treatment period

  • Cumulative number of Adverse Events and Serious Adverse Events during 30 days following completion of the treatment

    Cumulative number of Adverse Events and Serious Adverse Events during 30 days following completion of the treatment

    at each day during 30 days following completion of the treatment

Secondary Outcomes (1)

  • Change from baseline in Aphasia global test scores on standard aphasia test batteries at 1 and 30 days after completion of the treatment period

    at baseline, 1 and 30 days after completion of the treatment period

Study Arms (3)

rTMS

EXPERIMENTAL

Participants will receive real rTMS and sham tDCS

Device: rTMSDevice: Sham tDCS

tDCS

EXPERIMENTAL

Participants will receive real tDCS and sham rTMS

Device: tDCSDevice: Sham rTMS

Sham

SHAM COMPARATOR

Participants will receive both sham rTMS and sham tDCS

Device: Sham rTMSDevice: Sham tDCS

Interventions

rTMSDEVICE

Low frequency (1Hz) repetitive transcranial magnetic stimulation (rTMS) over the center of the right Pars Triangularis for 15 minutes (900 pulses) prior to each Speech-Language therapy session. Stimulation intensity will be set at 90% of the resting motor threshold (RMT) of the left first dorsal interosseous (FDI) muscle.

rTMS
tDCSDEVICE

2mA cathodal transcranial direct current stimulation (tDCS) over the right Pars Triangularis. The anode will be placed on the forehead over the contralateral eye. tDCS will start immediately before the speech-language therapy session and last throughout the session.

tDCS
Sham rTMSDEVICE

Low frequency (1Hz) repetitive transcranial magnetic stimulation (rTMS) over the Vertex for 15 minutes (900 pulses) prior to each Speech-Language therapy session. Stimulation intensity will be set at 10% of the resting motor threshold (RMT) of the left first dorsal interosseous (FDI) muscle.

ShamtDCS
Sham tDCSDEVICE

Sham cathodal transcranial direct current stimulation (tDCS) over the right Pars Triangularis. The anode will be placed on the forehead over the contralateral eye. To elicit the typical skin sensation of real tDCS (tingling sensation on the skin when tDCS is turned on and off), the current will be turned on for 30 seconds and then turned off for the duration of the speech-language therapy session. The same procedure will be done at the end of the session.

ShamrTMS

Eligibility Criteria

Age50 Years - 85 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • ischemic stroke in the left MCA territory
  • between 5 and 30 days post stroke
  • right-handedness
  • English, French or German as language of daily use
  • score below the lower limit of the norm on at least one of the primary outcome measures

You may not qualify if:

  • prior symptomatic ischemic or hemorrhagic stroke
  • severe comprehension deficit that may compromise informed consent or understanding of instructions
  • contraindications to MRI and/or TMS/tDCS
  • neurodegenerative or psychiatric disease
  • epilepsy or EEG-documented epileptic discharges
  • chronic renal or liver failure
  • life-threatening diseases
  • auditory or visual deficits that cannot be corrected and might impair testing

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Burke-Cornell Medical Research Institute

White Plains, New York, 10605, United States

Location

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

Location

Toronto Rehabilitation Institute - UHN

Toronto, Ontario, M5G 2C4, Canada

Location

CHUM Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Max-Planck-Institut für neurologische Forschung

Cologne, 50931, Germany

Location

Related Publications (2)

  • Zumbansen A, Black SE, Chen JL, J Edwards D, Hartmann A, Heiss WD, Lanthier S, Lesperance P, Mochizuki G, Paquette C, Rochon EA, Rubi-Fessen I, Valles J, Kneifel H, Wortman-Jutt S, Thiel A; NORTHSTAR-study group. Non-invasive brain stimulation as add-on therapy for subacute post-stroke aphasia: a randomized trial (NORTHSTAR). Eur Stroke J. 2020 Dec;5(4):402-413. doi: 10.1177/2396987320934935. Epub 2020 Jun 30.

    PMID: 33598559BACKGROUND
  • Zumbansen A, Kneifel H, Lazzouni L, Ophey A, Black SE, Chen JL, Edwards D, Funck T, Hartmann AE, Heiss WD, Hildesheim F, Lanthier S, Lesperance P, Mochizuki G, Paquette C, Rochon E, Rubi-Fessen I, Valles J, Wortman-Jutt S, Thiel A; NORTHSTAR-study group. Differential Effects of Speech and Language Therapy and rTMS in Chronic Versus Subacute Post-stroke Aphasia: Results of the NORTHSTAR-CA Trial. Neurorehabil Neural Repair. 2022 Apr;36(4-5):306-316. doi: 10.1177/15459683211065448. Epub 2022 Mar 25.

MeSH Terms

Conditions

AphasiaIschemic Stroke

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Speech DisordersLanguage DisordersCommunication DisordersNeurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and SymptomsStrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesVascular DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

Electric Stimulation TherapyTherapeuticsConvulsive TherapyPsychiatric Somatic TherapiesBehavioral Disciplines and ActivitiesElectroshockPsychological Techniques

Study Officials

  • Alexander Thiel, M.D.

    Jewish General Hospital (Montreal, Quebec)

    PRINCIPAL INVESTIGATOR
  • Sandra Black, M.D.

    Sunnybrook Research Institute (Toronto, Ontario)

    PRINCIPAL INVESTIGATOR
  • Elizabeth Rochon, Ph.D.

    Toronto Rehabilitation Institute - UHN

    PRINCIPAL INVESTIGATOR
  • Sylvain Lanthier, M.D.

    Hôpital Notre-Dame (Montreal, Quebec)

    PRINCIPAL INVESTIGATOR
  • Wolf-Dieter Heiss, M.D.

    Max-Planck-Institut fur Neurologische Forschung (Cologne, Germany)

    PRINCIPAL INVESTIGATOR
  • Dylan Edwards, Ph.D.

    Burke-Cornell Medical Research Institute (New-York)

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDIV
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Alexander Thiel, MD, Associate Professor.

Study Record Dates

First Submitted

December 10, 2013

First Posted

December 24, 2013

Study Start

December 1, 2013

Primary Completion

March 1, 2018

Study Completion

March 1, 2018

Last Updated

October 26, 2021

Record last verified: 2021-10

Locations