NCT03090711

Brief Summary

Brain functions are supported by multiple cell types, including neuronal and non-neuronal cells that are connected into complex networks. When the connectivity between those cells is altered or disrupted, the functioning of the brain is impaired. In stroke, the interruption of blood supply to the neural circuits results in connectivity damage and permanent disabilities. Experimental evidence suggests that some types of brain state, including sleep, can protect brain tissue from stroke and "repair" the damaged circuits. This project will investigate the neuronal mechanism underlying the protective effect of sleep on brain connectivity and network activity. To this end, the investigators will use a collection of state-of-the-art technologies including high-density electroencephalography (hd-EEG), transcranial magnetic stimulation (TMS) and transcranial alternating current stimulation (tACS). Perspectives include a better understanding of the causes and consequences of the perturbed electrical activity of the brain during sleep in stroke patients.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
21

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Aug 2017

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

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

First Submitted

Initial submission to the registry

March 9, 2017

Completed
18 days until next milestone

First Posted

Study publicly available on registry

March 27, 2017

Completed
4 months until next milestone

Study Start

First participant enrolled

August 2, 2017

Completed
3.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2020

Completed
Last Updated

May 3, 2021

Status Verified

April 1, 2021

Enrollment Period

3.2 years

First QC Date

March 9, 2017

Last Update Submit

April 30, 2021

Conditions

Hemispatial Neglect

Outcome Measures

Primary Outcomes (2)

  • Change from baseline in visual exploration and sleep parameters and the effect of cTBS

    Relationship of visual exploration (mean cumulative fixation duration) to sleep parameters (slow wave activity and spindles) from the baseline to post-cTBS sleep.

    Day 3

  • Change from baseline in the effect of tACS on visual exploration

    Group comparison of visual exploration task (mean cumulative fixation duration) between real and sham tACS.

    Day 2

Secondary Outcomes (2)

  • The effect of cTBS on sleep

    Day 1 to 3

  • The effect of tACS on sleep

    Day 1 to 2

Study Arms (4)

TMS

EXPERIMENTAL

Real transcranial magnetic stimulation (TMS).

Device: Transcranial Magnetic Stimulation (TMS)

sham TMS

SHAM COMPARATOR

Sham transcranial magnetic stimulation (TMS) as a comparison.

Device: sham Transcranial Magnetic Stimulation (TMS)

TMS and tACS

EXPERIMENTAL

Real transcranial magnetic stimulation (TMS) and real transcranial alternating current stimulation (tACS).

Device: Transcranial Magnetic Stimulation (TMS)Device: Transcranial Alternating Current Stimulation (tACS)

TMS and sham tACS

SHAM COMPARATOR

Real transcranial magnetic stimulation (TMS) and sham transcranial alternating current stimulation (tACS) as a comparison.

Device: Transcranial Magnetic Stimulation (TMS)Device: sham Transcranial Alternating Current Stimulation (tACS)

Interventions

Transcranial Magnetic Stimulation (TMS)DEVICE

The investigators recently showed that the repeated application of the so-called continuous theta burst protocol (cTBS) over the contralesional hemisphere resulted in a long-standing improvement of visual hemineglect (Cazzoli et al., 2012). The cTBS protocol was developed by Huang et al. (Huang et al., 2005) and modified by the investigators' group (Nyffeler et al., 2006). TBS protocol consists of a burst of 3 pulses at a frequency of 30 Hz, repeated at 6 Hz. One continuous train includes 801 pulses, the duration of one cTBS train is 44 seconds.

TMSTMS and sham tACSTMS and tACS
Transcranial Alternating Current Stimulation (tACS)DEVICE

TACS stimulation involves two electrodes placed on either side of the desired site of cortical stimulation. The mode of stimulation used in this experiment is identical to previous studies using tACS in sleep ( Marshall et al., 2006; Prehn-Kristensen et al., 2014 ). Stimulation follows a sinusoidal pattern from 0 to 260 μA. This pattern is delivered at 0.75 Hz and is repeated for 225 cycles; a total of 5 minutes of stimulation. This 5 minute pattern is again repeated 5 times, with a minute of no stimulation between each; thus for a total of 30 minutes.

TMS and tACS
sham Transcranial Magnetic Stimulation (TMS)DEVICE

Sham coil will be used to exclude possible nonspecific effects of the TMS. The sham coil is shielded i.e., the magnetic field output is weakened and therefore insufficiently powerful to stimulate the cortex.

sham TMS
sham Transcranial Alternating Current Stimulation (tACS)DEVICE

Sham stimulation will be used to exclude possible nonspecific effects of the tACS. Sham tACS stimulation will involve actual stimulation for the first 30 seconds of the ramp-up period (stimulation power is gradually increased until its final level), and then immediately gradually decreased until zero (without the intermediate 4 minutes of actual stimulation). This procedure will be repeated 5 times every 6 minutes and shall induce similar cutaneous sensations as real stimulation.

TMS and sham tACS

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Informed consent as documented by signature
  • Age between 18 and 80 years
  • First-ever right-sided stroke
  • Normal or corrected to normal vision
  • Demonstration of left hemispatial neglect (after a right-hemispheric brain lesion) found in a comprehensive neuropsychological test battery and clinical assessment
  • At least 3 weeks post-stroke

You may not qualify if:

  • Concomitant neurodegenerative diseases
  • Psychiatric diseases
  • Decompressive craniectomy
  • History of documented sleep disorders in the medical record (e.g. insomnia, hypersomnia, rem-sleep behaviour disorder)
  • Epileptic seizures
  • Implanted medical devices (e.g.: pacemakers, cochlear implants, implanted neurostimulators)
  • Presence of metal in the region of the head (excluding fixed dental implants such as tooth fillings or fixed dental braces)
  • Medication with drugs possibly lowering the seizure threshold
  • Alcohol or drug abuse
  • Inability to follow the procedures of the study
  • For female patients: in order to participate in the study, female patients in reproductive age need to take a pregnancy test (a standard urine pregnancy test will be provided).

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Department of Neurology, Inselspital, Bern University Hospital

Bern, 3010, Switzerland

Location

Related Publications (4)

  • Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC. Theta burst stimulation of the human motor cortex. Neuron. 2005 Jan 20;45(2):201-6. doi: 10.1016/j.neuron.2004.12.033.

    PMID: 15664172BACKGROUND

  • Nyffeler T, Wurtz P, Luscher HR, Hess CW, Senn W, Pflugshaupt T, von Wartburg R, Luthi M, Muri RM. Repetitive TMS over the human oculomotor cortex: comparison of 1-Hz and theta burst stimulation. Neurosci Lett. 2006 Nov 27;409(1):57-60. doi: 10.1016/j.neulet.2006.09.011. Epub 2006 Oct 17.

    PMID: 17049743BACKGROUND

  • Cazzoli D, Muri RM, Schumacher R, von Arx S, Chaves S, Gutbrod K, Bohlhalter S, Bauer D, Vanbellingen T, Bertschi M, Kipfer S, Rosenthal CR, Kennard C, Bassetti CL, Nyffeler T. Theta burst stimulation reduces disability during the activities of daily living in spatial neglect. Brain. 2012 Nov;135(Pt 11):3426-39. doi: 10.1093/brain/aws182. Epub 2012 Jul 24.

    PMID: 22831781RESULT

  • Marshall L, Helgadottir H, Molle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature. 2006 Nov 30;444(7119):610-3. doi: 10.1038/nature05278. Epub 2006 Nov 5.

    PMID: 17086200RESULT

MeSH Terms

Conditions

Perceptual Disorders

Interventions

Transcranial Magnetic StimulationTranscranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Neurobehavioral ManifestationsNeurologic ManifestationsNervous System DiseasesSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeuticsElectric Stimulation TherapyConvulsive TherapyPsychiatric Somatic TherapiesBehavioral Disciplines and ActivitiesElectroshockPsychological Techniques

Study Officials

  • Claudio L. Bassetti, Prof. Dr. med.

    Department of Neurology, Inselspital, Bern University Hospital

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
PARTICIPANT
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 9, 2017

First Posted

March 27, 2017

Study Start

August 2, 2017

Primary Completion

October 1, 2020

Study Completion

October 1, 2020

Last Updated

May 3, 2021

Record last verified: 2021-04

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)