Early Neurophysiological Interventions in Acute Cerebral Lesions

NCT04178395 | Completed DMC

• 1 other identifier: 110932
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Objective: Transcranial direct current stimulation (tDCS) can change the excitability of the central nervous system and contribute to motor recovery of stroke patients. The investigators hypothesized that the benefit of tDCS may increase with interventions facilitating motor responses, such as repetitive peripheral nerve stimulation (rPNS). The aim of our study was to examine the short and long-term effects of real vs sham bihemispheric tDCS on scales of motor function and neurophysiological tests in patients with acute stroke and a moderate/severe motor impairment. Methods: The study was prospective, randomized, double-blind and placebo controlled. Twenty acute stroke patients (ischemic and haemorrhagic) with Upper limb Fugl-Meyer (ULFM) score\<19 were randomized in two parallel groups: one group received 5 consecutive daily sessions of anodal tDCS over the affected hemisphere (AH) and cathodal over unaffected hemisphere combined with rPNS and the other received sham tDCS associated to rPNS. Pacients were examined before tDCS, 5 days and 3, 6 and 12 months after tDCS. The investigators evaluated ULFM and modified Ashworth scales (MAS), resting motor threshold, motor and somatosensory evoked potentials (MEPs and SEPs), silent periods and Hmax/Mmax ratio.

Conditions

Stroke; Acute Stroke

Keywords

transcranial direct current stimulation; stroke rehabilitation; neuromodulation; corticomotor excitability; repetitive peripheral nerve stimulation

Outcome Measures

Primary Outcomes (7)

• Upper limb Fugl-Meyer scale

  Motor assessment stroke-specific, performance-based impairment index, designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia. Unit of measure 0-66 (higher scores reflect better outcome)

  one year

• Modified Ashworth scale

  Measures resistance during passive soft-tissue stretching and is used as a simple measure of spasticity. Unit of measure 0-4 (higher scores reflect increase spasticity)

  one year

• Resting motor threshold

  Corticomotor excitability measure is the lowest stimulator output at the optimal scalp site required to elicit a MEP of at least 50 μV. Unit of measure: % of maximal stimulator output.

  one year

• Contralateral and ipsilateral silent period

  Evaluates corticomotor excitability of each hemisphere and transcallosal contralateral's hemisphere influence. Transcranial magnetic stimulation is applied over the M1 area of each hemisphere while patients sustained a steady maximum tonic contraction of the muscle and ipsilateral and contralateral responses of both upper limbs are recorded. Unit of measure: miliseconds

  one year

• Motor evoked potentials

  Motor evoked potentials refers to the action potential elicited by noninvasive stimulation of the motor cortex through the scalp. Unit of measure: milivolts

  one year

• Somatosensory evoked potentials

  Somatosensory evoked potentials are the electrical activity of the brain that results from the stimulation of the somatosensory system, through electrical stimulation. Unit of measure: microvolts.

  one year

• Hmax/Mmax ratio

  H reflex, the electrical analogue of the spinal stretch reflex, allowed the investigators to study spinal circuitry excitability. The index Hmax/Mmax ratio was compared between the paretic and the non-paretic arm and is considered a neurophysiological measure of spasticity. Unit of measure: %

  one year

Study Arms (2)

real tDCS group

EXPERIMENTAL

Patients allocated to the real tDCS group (11 patients) received one daily session of bihemispheric transcranial direct stimulation and repetitive peripheral stimulation for 5 consecutive days.

Device: bihemispheric transcranial direct stimulation

sham group

SHAM COMPARATOR

Patients allocated to the sham tDCS group (9 patients) received sham tDCS + rPNS also daily, for 5 consecutive days.

Device: bihemispheric transcranial direct stimulation

Interventions

bihemispheric transcranial direct stimulation DEVICE

tDCS was applied with the anode placed over the M1 hand area of the ipsilesional motor cortex and the cathode over the same area of the contralesional motor cortex (C3/C4). For the active condition, patients received 5 consecutive daily sessions of 2 mA anodal tDCS over the AH and cathodal tDCS over the UH of 20 minutes each, with fade-in and fade-out periods of 1s. For the sham condition, the stimulation applied in the same sites and with the same parameters, was turned off after a fade-in period, 30 seconds of direct current stimulation and a fade-out period. Repetitive peripheral nerve stimulation was performed by a peripheral nerve stimulator to the radial nerve and applied at the same time as tDCS. Radial nerve was chosen to improve wrist extension. Trains of 40 stimuli (ISI: 10 ms, duration: 1ms) were delivered every 6 seconds to the radial nerve through bipolar electrodes (5 cm diameter) at an intensity that could elicit a visible wrist extension (20-30 mA).

Also known as: repetitive peripheral stimulation

real tDCS group; sham group

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• first time single and unilateral supratentorial stroke confirmed by CT or MRI.
• stroke interval between 5 and 20 days of study onset.
• age 18 to 79 years,
• National Institutes of Health Stroke Scale (NIHSS) ≥6 and ≤21.

You may not qualify if:

• preceding epileptic seizures.
• metallic implants within the brain or pacemaker implants.
• coexistence of other neurological diseases

Sponsors & Collaborators

• Sara Yagüe MD: lead
• Hospital Clinic of Barcelona: collaborator

Study Sites (1)

Bellvitge University Hospital

Barcelona, 08907, Spain

Location

Related Publications (6)

• Kandel M, Beis JM, Le Chapelain L, Guesdon H, Paysant J. Non-invasive cerebral stimulation for the upper limb rehabilitation after stroke: a review. Ann Phys Rehabil Med. 2012 Dec;55(9-10):657-80. doi: 10.1016/j.rehab.2012.09.001. Epub 2012 Sep 29. English, French.

  PMID: 23084320 RESULT

• Nitsche MA, Paulus W. Excitability changes induced in the human motor cortex by weak transcranial direct current stimulation. J Physiol. 2000 Sep 15;527 Pt 3(Pt 3):633-9. doi: 10.1111/j.1469-7793.2000.t01-1-00633.x.

  PMID: 10990547 RESULT

• Sattler V, Acket B, Raposo N, Albucher JF, Thalamas C, Loubinoux I, Chollet F, Simonetta-Moreau M. Anodal tDCS Combined With Radial Nerve Stimulation Promotes Hand Motor Recovery in the Acute Phase After Ischemic Stroke. Neurorehabil Neural Repair. 2015 Sep;29(8):743-54. doi: 10.1177/1545968314565465. Epub 2015 Jan 7.

  PMID: 25567120 RESULT

• Rossi C, Sallustio F, Di Legge S, Stanzione P, Koch G. Transcranial direct current stimulation of the affected hemisphere does not accelerate recovery of acute stroke patients. Eur J Neurol. 2013 Jan;20(1):202-4. doi: 10.1111/j.1468-1331.2012.03703.x. Epub 2012 Mar 26.

  PMID: 22448901 RESULT

• Hesse S, Waldner A, Mehrholz J, Tomelleri C, Pohl M, Werner C. Combined transcranial direct current stimulation and robot-assisted arm training in subacute stroke patients: an exploratory, randomized multicenter trial. Neurorehabil Neural Repair. 2011 Nov-Dec;25(9):838-46. doi: 10.1177/1545968311413906. Epub 2011 Aug 8.

  PMID: 21825004 RESULT

• Rabadi MH, Aston CE. Effect of Transcranial Direct Current Stimulation on Severely Affected Arm-Hand Motor Function in Patients After an Acute Ischemic Stroke: A Pilot Randomized Control Trial. Am J Phys Med Rehabil. 2017 Oct;96(10 Suppl 1):S178-S184. doi: 10.1097/PHM.0000000000000823.

  PMID: 28837443 RESULT

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Jordi Montero, PhD

  Hospital Universitari de Bellvitge

  PRINCIPAL INVESTIGATOR

• Josep Valls-Solé, PhD

  Clinic Hospital of Barcelona

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Trained investigators, blinded to group assignment, performed the patients' neurostimulation. Patients were also blinded to the type of stimulation they were going to receive. Patients were randomized in 2 parallel groups. A serial number from a computer-generated randomization list was given to each patient for group allocations. Patients allocated to the real tDCS group (11 patients) received one daily session of bihemispheric tDCS + rPNS for 5 consecutive days. The patients allocated to the sham tDCS group (9 patients) received sham tDCS + rPNS also daily, for 5 consecutive days. Group allocation of each patient was only disclosed for analysis of data after the end of all evaluations, 1 year after treatment application. Outcome assessor was also blind to group assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-investigator

Model Details: The study was prospective, randomized, double-blind and placebo controlled. Twenty acute stroke patients (ischemic and haemorrhagic) with Upper limb Fugl-Meyer (ULFM) score\<19 were randomized in two parallel groups: one group received 5 consecutive daily sessions of anodal transcranial direct current stimulation (tDCS) over the affected hemisphere and cathodal over unaffected hemisphere combined with repetitive peripheral nerve stimulation (rPSN) and the other received sham tDCS associated to rPNS. Patients were examined before tDCS, 5 days and 3, 6 and 12 months after tDCS.

Study Record Dates

• First Submitted: November 21, 2019
• First Posted: November 26, 2019
• Study Start: April 8, 2011
• Primary Completion: December 31, 2011
• Study Completion: November 9, 2013
• Last Updated: November 26, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: When the manuscript is accepted.
• Access Criteria: Open access in the scientific journal where the manuscript is accepted.

Locations

ES (1)