Clinical trial NCT02910024: Theta-Burst-Stimulation in Early Rehabilitation of Stroke
Official title: Theta-Burst-Stimulation in Der frühen Rehabilitation Von Schlaganfallpatienten
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Stroke
Lead sponsor: University of Cologne
Sponsor class: OTHER
First posted: 2016-09-21
Enrollment: 150
Sex: ALL
Minimum age (years): 40
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The present prospective, randomized, controlled, double-blinded trial investigates the effects of intermittent theta-burst stimulation (iTBS) during the early rehabilitation after stroke. Patients with hemipresis will receive either sham or real iTBS over their affected hemispheres before occupational therapy for 8 days. Motor recovery is assessed one day after the intervention phase and three months after enrollment.

Detailed description: To date, rehabilitation of stroke with hemiparesis mainly includes physiotherapy and occupational therapy. Yet, the majority of patients retain movement impairment relevant for activities of daily living. One explanation for this deficit is the insufficient recovery of connectivity between brain regions after stroke. It is possible to modulate this process by repetitive transcranial magnetic stimulation (rTMS) using the protocol of intermittent theta-burst stimulation (iTBS). Previous data indicate that modulation of the motor cortex with iTBS enhances the effects of subsequent motor training. The present study aims at investigating whether daily repetitive transcranial magnetic stimulation over 8 days combined with subsequent physiotherapy leads to better motor recovery, compared with physiotherapy after sham stimulation. In the first weeks and after three months, motor function, degree of disability and quality of life are examined in order to evaluate the effects of iTBS in the rehabilitation of stroke patients.

Amendment (approved by the Ethics-Committee of the Medical Faculty of the University of Cologne, 20/12/2016): Specification of exclusion criteria.

Amendment (approved by the Ethics-Committee of the Medical Faculty of the University of Cologne, 15/11/2018): Change of inclusion and exclusion criteria.

Eligibility criteria: Inclusion Criteria:

* written consent
* age: 40-90 years
* ischemic stroke
* hemiparesis with impaired hand motor function

Exclusion Criteria:

* Subjects who are legally detained in an official institute (§20 MPG)
* Participation in clinical trial within the last 12 weeks
* Electronic implants or ferromagnetic Implants located in the head, neck or thorax (e.g. clips, intracranial shunt, artificial heart valve, pacemaker)
* Medication pump (e.g. insulin pump)
* Metal splinters in eye or head
* Pregnancy / breastfeeding
* Severe Neurodegenerative disease
* Severe Neuroinflammatory disease
* History of seizures / epilepsy
* Physical addiction to alcohol, medication, or drugs (excluded: nicotine)
* Insufficient compliance
* Present or past malignant tumor involving the central nervous system
* Severe Psychiatric disease
* Clinically manifest bilateral hemiparesis or infarcts in the primary motor cortex or along the tractus corticospinalis in the hemisphere ipsilateral to the hemiparesis
* Pre-existing cerebral infarctions with hemiparesis or pre-existing cerebral infarctions in the primary motor cortex or along the tractus corticospinalis, excluding microangiopathic changes (e.g. clinically asymptomatic lacunae \<1cm)
* Known brain lesion (surgical, traumatic)
* Evidence for enhanced cerebral pressure
* Severe cardial dysfunction
* life expectancy \< 12 months
* NIHSS Score \> 20
* Blood glucose imbalances resistant to treatment (\<50 mg/dl or \>300 mg/dl)
* Elevated blood pressure resistant to treatment (RR \> 185/110mmHg)
* Systemic Thrombolysis using r-tPA or thrombectomy within the last 24 hours before enrollment in study
* Medication with benzodiazepines, high-potency antipsychotics or tricyclic antidepressants before hospitalization or long-term during hospitalization

Primary outcomes:
measure: Relative grip force
timeFrame: 3 months after enrollment
Secondary outcomes:
measure: Relative grip force
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Motor function
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Motor function
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Stroke severity
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Degree of disability
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Motorcortex excitability
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Motorcortex excitability
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Quality of life
timeFrame: after 8 days of intervention, and 3 months after enrollment
measure: Activities of daily living at admission and discharge in external rehabilitation facility
timeFrame: 3 months after enrollment
measure: Days of rehabilitation after intervention phase
timeFrame: 3 months after enrollment
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Klinik und Poliklinik für Neurologie, Universitätsklinikum Köln
state: North Rhine-Westphalia
Study officials:
affiliation: University of Cologne
name: Gereon R Fink, Univ.-Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hensel L, Grefkes C, Tscherpel C, Ringmaier C, Kraus D, Hamacher S, Volz LJ, Fink GR. Intermittent theta burst stimulation applied during early rehabilitation after stroke: study protocol for a randomised controlled trial. BMJ Open. 2019 Dec 30;9(12):e034088. doi: 10.1136/bmjopen-2019-034088.