Multichannel tDCS to Reduce Hypertonia in Patients With Prolonged DOC

• ClinicalTrials.gov Identifier: NCT03797573
• Recruitment Status: Completed
• First Posted: January 9, 2019
• Last Update Posted: January 9, 2019
• Sponsor: University of Liege
• Information provided by (Responsible Party): Aurore Thibaut, University of Liege

Study Description

Brief Summary:

Previous studies showed that transcranial direct current stimulation (tDCS) transiently improves performance of motor function in stroke patients, as well as decrease muscle hypertonia. In severely brain injured patients with disorders of consciousness (DOC), a single stimulation over the left dorsolateral prefrontal cortex has shown to improve patients' sign of consciousness. Nevertheless, other brain areas could be stimulated in order to manage other symptoms occurring in this population of patients, such as muscle hypertonia. In this study, investigators will assess the effects of bilateral fronto-central tDCS on spasticity as measured with the Modified Ashworth Scale (MAS) and on the Coma Recovery Scale-Revised (CRS-R) scores in patients with DOC in a double-blind sham-controlled experimental design.

Condition or disease	Intervention/treatment	Phase
Vegetative State; Minimally Conscious State; Spasticity, Muscle; Disorder of Consciousness	Device: tDCS; Device: sham tDCS	Phase 1

Detailed Description:

Following severe brain damage and coma, some patients may remain in a vegetative state (VS) or minimally conscious state (MCS). At present, there are no evidence-based guidelines regarding the treatment of patients with disorders of consciousness (DOC). A previous study showed that a single stimulation (using transcranial direct current stimulation - tDCS) of the left prefrontal cortex induces an behavioral improvement in some patients in DOC. Nevertheless, patients with DOC suffer from other invalidating dysfunctions such as spasticity (muscle hypertonia). In sroke patients, the inhibition of the motor cortex through cathodes placed over the motor region showed to reduce spasticity.

In this study, investigators aim to assess the effect of single session of transcranial direct current stimulation (tDCS) over right and left fronto-central areas (using 2 anodes and 2 cathodes), on the level of hypertonia and the level of consciousness of patients with DOC, in a double blind randomized sham controlled study. The anodes will be placed over F3 and F4, and the cathodes over C3 and C4.

tDCS is a form of safe non-invasive cortical stimulation, modulating cortical excitability under the electrodes, via weak polarizing currents. It has been reported that anodal tDCS transiently improves motor functions in healthy subjects and patients with stroke or Parkinson's disease.

By reducing the activity of the motor cortex (cathodes) and increasing the activity of the prefrontal cortex (anodes) we expect to observe a better motor function in patients with DOC.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Multichannel Transcranial Direct Current Stimulation to Reduce Hypertonia in Patients With Prolonged Disorders of Consciousness: a Pilot Study.
• Actual Study Start Date: January 20, 2014
• Actual Primary Completion Date: June 28, 2014
• Actual Study Completion Date: December 13, 2017

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: active tDCS; Patients will receive tDCS (bilateral fronto-central stimulation) during 20 minutes preceded and followed by a clinical assessment (Modified Ashworth Scale and Coma Recovery Scale-Revised) and neurophysiological assessment (8 channels EEG).	Device: tDCS; tDCS will be applied during 20 minutes with a current of 1 mA preceded and followed by a behavioral assessments (Modified Ashworth Scale and Coma Recovery Scale Revised) and an EEG. The anodes will be placed over F3 and F4 and the cathodes over C3 and C4.
Sham Comparator: sham tDCS; Patients will receive sham tDCS (5 seconds of stimulation) during 20 minutes preceded and followed by a clinical assessment (Modified Ashworth Scale and Coma Recovery Scale-Revised) and neurophysiological assessment (8 channels EEG).	Device: sham tDCS; Indentical to the active tDCS, except that the stimulation is terminated after 5 seconds.

Outcome Measures

Primary Outcome Measures :

1. Change in MAS scores [ Time Frame: baseline and directly after tDCS (20 minutes) ]
   Modified Ashworth Scale (MAS) will by assessed before and after tDCS (active and sham). Comparison of treatment effect (MAS score after tDCS minus before) between active and sham tDCS. The MAS is a 5 points scale going from 0 (no spasticity) and 5 (extreme spasticity).

Secondary Outcome Measures :

1. Change in the CRS-R total score [ Time Frame: Baseline and directly after the tDCS (20 minutes)] ]
   Coma Recovery Scale Revised (CRS-R) will be performed before and after tDCS (anodal and sham). Comparison of the treatment effect (CRS-R total score score after tDCS minus before) between real and sham tDCS. The CRS-R is 23 points scale with 6 sub-scales (lower scores refer to reflexes, while higher scores refer to more complex behaviors). The total score is the sum of the scores in the 6 sub-scales.
2. Change in brain oscillations [ Time Frame: Baseline and directly after the tDCS (20 minutes) ]
   8 channels electroencephalography (EEG) will be record before and after tDCS to record potential cortical changes induce by the stimulation. EEG power will be compared in different bandwidths (delta, theta, alpha, beta).

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 75 Years (Child, Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• post comatose patients
• patients in minimally conscious state
• patients with stable condition
• patients free of sedative drugs and Na+ or Ca++ blockers (e.g., carbamazepine) or NMDA receptor antagonist (e.g., dextromethorphan)

Exclusion Criteria:

• premorbid neurology antecedent
• patients in coma
• patients < 28 days after the acute brain injury
• patients with a metallic cerebral implant
• cranioplasty
• shunt

Contacts and Locations

Locations

Belgium

University of Liege

Liege, Belgium, 4000

Sponsors and Collaborators

University of Liege

More Information

Publications:

Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26.

• Responsible Party: Aurore Thibaut, Principal Investigator, University of Liege
• ClinicalTrials.gov Identifier: NCT03797573
• Other Study ID Numbers: 2014/280B
• First Posted: January 9, 2019
• Last Update Posted: January 9, 2019
• Last Verified: January 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Aurore Thibaut, University of Liege:

transcranial direct current stimulation; disorder of consciousness; muscle hypertonia; spasticity; vegetative state; minimally conscious state

Additional relevant MeSH terms:

Muscle Spasticity; Consciousness Disorders; Persistent Vegetative State; Muscle Hypertonia; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Neurobehavioral Manifestations; Neurocognitive Disorders; Mental Disorders; Brain Damage, Chronic; Brain Diseases; Central Nervous System Diseases; Unconsciousness