Transcranial Direct Current Stimulation Combined Sensory Modulation Intervention in Chronic Stroke Patients

NCT01847157 | Completed

• 1 other identifier: 201202016RIB
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

Background and purpose: About 30% of people with stroke suffered from severe long-term upper extremity （UE） motor impairment. Severe UE impairment, especially dysfunction of hand, can greatly impact stroke patients' daily living independence and quality of life. However, treatment effect of current interventions is still limited. Nick Ward and Leonardo Cohen suggested 5 intervention strategies for stroke motor recovery: （1） reduction of somatosensory input from the intact; （2） increase in somatosensory input from the paretic; （3） anesthesia of a body part proximal to the paretic hand; （4） activity within the affected motor cortex may be up-regulated; （5） activity within the intact motor cortex may be down-regulated. Recent studies have shown each strategy to be effective in stroke patients with mild or moderate UE impairment. However, evidence for people with severe UE impairment after stroke remains unclear. Since research has found a greater effect for combined strategies than a single strategy, this proposal develops a combined intervention with the above 5 strategies, named "transcranial direct current stimulation （tDCS） combined sensory modulation intervention". This intervention is expected to be most effective for people with severe UE impairment after stroke. In addition, neuroimaging can provide in vivo information about the brain plasticity which underpinning the motor recovery after stroke. However, image indexes that can be used in stroke patients with severe UE impairment remained examined. Therefore, this proposal has 3 aims: （1） to examine the treatment effect of the "tDCS combined sensory modulation intervention" in stroke patients with severe UE impairment; （2） to examine the underline mechanism of the efficacy of "tDCS combined sensory modulation intervention" using neuroimaging technology. Methods: This study is a double-blinded randomized controlled trial which will recruit 60 people who have had stroke onset more than 6 months and have severe UE motor impairment. All participants will be randomly assigned into 2 groups. The experimental group will be given the "tDCS combined sensory modulation intervention", combining bilateral tDCS stimulation, anesthesia techniques and repetitive passive motor training. The control group is given sham tDCS, sham anesthesia and repetitive passive motor training. Each group will be evaluated for outcomes at 4 time points （i.e. baseline, post-intervention, 3 months and 6months post-intervention）. The immediate and long-term effect of the interventions will be examined. Primary outcome indicators include upper extremity impairment measures. Secondary outcome measures include upper extremity function, activities of daily living function, functional Magnetic Resonance Imaging （fMRI）, and corticospinal tract structural integrity using diffusion spectrum imaging （DSI）. Fifteen subjects of each group will be assessed 2 times （i.e., prior to the intervention and after the intervention） for fMRI and DSI scan. Anticipatory results and contributions: The results of the studies are expected to present a potentially effective intervention for stroke patients with severe impaired UE motor. Imaging evidence of brain plasticity for this particular intervention is also provided. The results will contribute to our understanding of brain plasticity for UE motor recovery after stroke. Findings from this proposal may help researchers and clinicians choose or develop interventions that are optimal to their clients individually.

Conditions

Stroke

Keywords

recovery of function; stroke; Upper extremity; Motor; transcranial direct current stimulation

Outcome Measures

Primary Outcomes (3)

• Change from baseline Fugl Meyer Assessment(FMA)upper extremities subscale after intervention

  FMA-UE estimates the movement of proximal upper extremity (including shoulder joint, elbow joint and forearm), wrist joint and hand. Each movement is estimated by 3 scaled rules (0-1-2): score 0 indicates that the patient has no movement at all; score 1 indicates that the patient can perform partial movements; score 2 indicates that the patient can normally perform all movements. The total score in the differential scale is 66, and a higher score indicates that the patient has better movement ability.

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

• Change from baseline Active joint activity after intervention

  A protractor is used to estimate 4 active joint activities of patients,including wrist extension, carpometacarpal extension, metacarpophalangeal extension, and shoulder flexion.

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

• Change from baseline Muscle tone after intervention

  Motor assessment scale (MAS) is used to estimate muscle tension in patients, and the estimated muscles include the flexors and extensors of elbow, wrist and metacarpophalangeal joints. MAS is totally divided into 6 scales (0, 1, 1+, 2, 3, 4), and a higher score indicates that the patient has higher muscle tension.

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

Secondary Outcomes (17)

• Change from baseline research arm test (ARAT) after intervention

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

• Change from baseline Barthel Index(BI) after intervention

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

• Change from baseline Patient Health Questionnaire (PHQ-9) after intervention

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

• Change from baseline fMRI activation after intervention

  Assessed at the baseline section (within 3 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 3 days after the latest intervention section)

• Change from baseline Diffusion Spectrum Imaging after intervention

  Assessed at the baseline section (within 7 days ahead to the 1st intervention section), and then again immediately following the 8 weeks intervention (within 7 days after the latest intervention section).

Study Arms (2)

tDCS & epidermis anesthesia & repeated passive movement

EXPERIMENTAL

The patients in the experiment group will receive multi-strategy combination treatment mode- "combined tDCS and sensory input regulation treatment mode", including bilateral tDCS , epidermis anesthesia in the proximal hand of affected side and in the distal hand of unaffected side , and repeated passive movement training for the hand of affected side. Treatment modes are 3 times a week, 30 minutes each time, lasting for 8 weeks, and totally 24 trainings. The treatment content of each strategy is separately described in the following.

Device: tDCS; Drug: Epidermis anesthesia; Other: Repeated passive movement

Shame tDCS & sham anesthesia & repeated passive movement

SHAM COMPARATOR

the control group is "repeated passive movement stimulation", including sham bilateral tDCS, sham epidermis anesthesia in the proximal hand of affected side and in the distal hand of unaffected side, and repeated passive movement training for the hand of affected side. Treatment modes are 3 times a week, 30 minutes each time, lasting for 8 weeks, and totally 24 trainings. The treatment content of each strategy is separately described in the following.

Drug: sham anesthesia; Other: Repeated passive movement; Device: sham tDCS

Interventions

tDCS DEVICE

Intelect mobile combination (Intelect, USA) is utilized as a direct current stimulator. The 25 cm2 electrodes on a sponge slice immersed in physiological salt solution are fixed on the left and right positions C3/ C4 of subject head (according to the international 10-20 system of electroencephalogram). During the treatment, 1.5 mA electric current is applied to stimulate the subjects in the experimental group for totally 30 minutes. At the start and the end of stimulation, the electric current will gradually increase from zero, or reduce to zero in 1 minute in order to avoid the possible appearance of slight flash effect of subject eyesight, which is caused by instantly turning on or turning off the electric current.

Also known as: Intelect mobile combination

tDCS & epidermis anesthesia & repeated passive movement

Epidermis anesthesia DRUG

15 g of Emla 5% Cream(anesthetic) is applied to the ventral surface of the forearm of unaffected side with a distance of 10 mm from the wrist, and an area of 150 mm long x 50 mm wide. Furthermore, 10 g Emla 5% Cream(anesthetic) is applied to the ventral surface of the upper arm of affected side with a distance of 10 mm from the wrist, and an area of 100 mm long x 50 mm wide.

Also known as: Emla 5% cream (Lignocaine 2.5% / Prilocaine 2.5%)

tDCS & epidermis anesthesia & repeated passive movement

sham anesthesia DRUG

15 g of 5% body Cream is applied to the ventral surface of the forearm of unaffected side with a distance of 10 mm from the wrist, and an area of 150 mm long x 50 mm wide. 10 g body Cream is applied to the ventral surface of the upper arm of affected side with a distance of 10 mm from the wrist, and an area of 100 mm long x 50 mm wide.

Also known as: Cetaphil, body cream

Shame tDCS & sham anesthesia & repeated passive movement

Repeated passive movement OTHER

Repeated passive wrist extension training: Patients' wrist joint are passively moved by a trained occupational therapist (joint moving angle = 0- 60 degree), frequency 1 Hz, maintain for 20 minutes. Finger passive flexion and extension training: Patients' fingers joint are passively moved by a trained occupational therapist, frequency 1 Hz, maintain for 10 minutes.

Shame tDCS & sham anesthesia & repeated passive movement; tDCS & epidermis anesthesia & repeated passive movement

sham tDCS DEVICE

The equipment of sham stimulation in the control group is exactly the same as the equipment in the experiment group. However, the only difference is that 30 seconds after the start of electric current, the experimenter turns off the powder under subject ignorance situation. The stimulation just gives patients weak sense of electric current, in order to blind them for which group they are in.

Also known as: Intelect mobile combination

Shame tDCS & sham anesthesia & repeated passive movement

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• first ever ischemic or hemorrhagic stroke patients identified by computed tomography (CT) or magnetic resonance imaging (MRI)
• age between 40 and 80 years old
• have a stroke over 6 months
• unilateral hemiplegia
• Fugl-Meyer assessment-upper extremity (FMA-UE) score≦29 when selection
• poststroke elbow flexor spasticity less than 2 using modified Ashworth scale (MAS)
• no severe anesthesia (FMA sensory test, upper extremity score≧10 )
• no wrist and finger joint pain
• clear consciousness, can understand simple sentences and spoken orders, and co-operate manipulation
• can accept motor training in the sitting position for approximately 30 minutes.

You may not qualify if:

• Suffer from other orthopedic diseases (such as severe arthritis), nerve damage (such as peripheral nerve damage), or severe pain, which influences upper extremity motor
• have a medical history or family history of epilepsy
• regularly take central nervous system drugs (such as sedatives), or the Class III antiarrhythmic drugs (such as amiodarone)
• have atopic dermatitis or skin disorders of the scalp
• have allergy to anesthetic medicines of the acyl amine
• have a metal implant in the head or neck, or serious arrhythmia (the heartbeat is less than 50 beats per minute or higher than 100 beats per minute); or use a pacemaker or atrial defibrillator

Sponsors & Collaborators

• National Taiwan University Hospital: lead
• National Science and Technology Council, Taiwan: collaborator

Study Sites (1)

National Taiwan University Hospital

Taipei, Taipei, 100, Taiwan

Location

Related Publications (8)

• Lindenberg R, Renga V, Zhu LL, Nair D, Schlaug G. Bihemispheric brain stimulation facilitates motor recovery in chronic stroke patients. Neurology. 2010 Dec 14;75(24):2176-84. doi: 10.1212/WNL.0b013e318202013a. Epub 2010 Nov 10.

  PMID: 21068427 BACKGROUND

• 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 BACKGROUND

• Stagg CJ, Nitsche MA. Physiological basis of transcranial direct current stimulation. Neuroscientist. 2011 Feb;17(1):37-53. doi: 10.1177/1073858410386614.

  PMID: 21343407 BACKGROUND

• Stagg CJ, Bachtiar V, O'Shea J, Allman C, Bosnell RA, Kischka U, Matthews PM, Johansen-Berg H. Cortical activation changes underlying stimulation-induced behavioural gains in chronic stroke. Brain. 2012 Jan;135(Pt 1):276-84. doi: 10.1093/brain/awr313. Epub 2011 Dec 6.

  PMID: 22155982 BACKGROUND

• Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A, Paulus W, Hummel F, Boggio PS, Fregni F, Pascual-Leone A. Transcranial direct current stimulation: State of the art 2008. Brain Stimul. 2008 Jul;1(3):206-23. doi: 10.1016/j.brs.2008.06.004. Epub 2008 Jul 1.

  PMID: 20633386 BACKGROUND

• Weiss T, Sens E, Teschner U, Meissner W, Preul C, Witte OW, Miltner WH. Deafferentation of the affected arm: a method to improve rehabilitation? Stroke. 2011 May;42(5):1363-70. doi: 10.1161/STROKEAHA.110.601138. Epub 2011 Mar 31.

  PMID: 21454817 BACKGROUND

• Ward NS, Cohen LG. Mechanisms underlying recovery of motor function after stroke. Arch Neurol. 2004 Dec;61(12):1844-8. doi: 10.1001/archneur.61.12.1844.

  PMID: 15596603 BACKGROUND

• Koh CL, Lin JH, Jeng JS, Huang SL, Hsieh CL. Effects of Transcranial Direct Current Stimulation With Sensory Modulation on Stroke Motor Rehabilitation: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2017 Dec;98(12):2477-2484. doi: 10.1016/j.apmr.2017.05.025. Epub 2017 Jun 24.

  PMID: 28652065 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Transcranial Direct Current Stimulation; Lidocaine, Prilocaine Drug Combination; Lidocaine; cetyl alcohol, propylene glycol, sodium lauryl sulfate non-lipid cleansing lotion

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques; Acetanilides; Anilides; Amides; Organic Chemicals; Prilocaine; Aniline Compounds; Amines; Drug Combinations; Pharmaceutical Preparations

Study Officials

• Jiann-Shing Jeng, Doctor

  Department of Neurology, National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: May 6, 2013
• Study Start: January 1, 2013
• Primary Completion: June 1, 2015
• Study Completion: June 1, 2015
• Last Updated: February 18, 2016

Record last verified: 2016-02

Locations

TW (1)