Sleep as a Model to Understand and Manipulate Cortical Activity in Order to Promote Functional Recovery After Stroke

Hemispatial Neglect Clinical Trial

— SSS  

Official title:

Sleep as a Model to Understand and Manipulate Cortical Activity in Order to Promote Neuroplasticity and Functional Recovery After Stroke

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03090711
• Other study ID #: 2016-01387
• Status: Completed
• Phase: N/A
• Start date: August 2, 2017
• Est. completion date: October 1, 2020

Study information

• Verified date: April 2021
• Source: University Hospital Inselspital, Berne
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: October 1, 2020
• Est. primary completion date: October 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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).

Related Conditions & MeSH terms

• Hemispatial Neglect
• Perceptual Disorders

Intervention

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

Locations

Country	Name	City	State
Switzerland	Department of Neurology, Inselspital, Bern University Hospital	Berne

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Inselspital, Berne

Country where clinical trial is conducted

Switzerland, 

References & Publications (4)

Cazzoli D, Müri 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 livi — View Citation

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. — View Citation

Marshall L, Helgadóttir H, Mölle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature. 2006 Nov 30;444(7119):610-3. Epub 2006 Nov 5. — View Citation

Nyffeler T, Wurtz P, Lüscher HR, Hess CW, Senn W, Pflugshaupt T, von Wartburg R, Lüthi M, Müri 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. Epub 2006 Oct 17. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	The effect of cTBS on sleep	Relationship between baseline sleep parameters (slow wave activity and spindles) and effectiveness of cTBS.	Day 1 to 3
Secondary	The effect of tACS on sleep	Change in sleep architecture (REM and NREM sleep) between tACS and sham stimulation.	Day 1 to 2