Clinical trial NCT05119881: Combine Mirror Therapy and tDCS on CPSP
Official title: Effect of Mirror Therapy and tDCS on Central Poststroke Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke
Pain
Keywords: central poststroke pain
mirror therapy
transcranial direct current stimulation
transcranial magnetic stimulation
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2021-11-15
Enrollment: 7
Sex: ALL
Minimum age (years): 20
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 3 groups of different interventions
Primary purpose: TREATMENT

Brief summary: Central poststroke pain (CPSP) refers to the symptom of pain arising after a stroke. Patients with CPSP often complain of various painful or unpleasant sensation. Feelings of pain may interfere with sleep and hugely affect the patients' quality of life. Non-invasive brain stimulation, such as transcranial direct current stimulation (tDCS), is an emerging nonpharmacological treatment and has been shown to have promising pain reduction effects for patients with CPSP. Mirror therapy (MT), on the other hand, is a contemporary approach that has often been used to facilitate upper extremity motor recovery in patients with stroke. MT has been shown to be effective in ameliorating sensory deficits and reducing shoulder pain. To date, no study has determined whether combining MT with tDCS could reduce pain in patients with CPSP. The goal of this study is to determine the effect of combining MT and tDCS on pain, sensation, motor function, and quality of life in people with CPSP.

Forty-five patients with CPSP will be randomly allocated to one of the 3 groups: combining MT with tDCS (MT+tDCS) group, MT with sham tDCS (MT+s-tDCS) group, and sham MT with tDCS (s-MT+tDCS) group. The participants in all groups will receive intervention 30 minutes/day, 3 days/ week, for 3 weeks. The participants in the MT+tDCS group will receive tDCS applied simultaneously with MT for 20 minutes. For the following 10 minutes, the tDCS will be turned off while the electrodes will be kept on the scalp, and the participants will continue with MT. For the MT+s-tDCS group, same tDCS procedures will be applied to the participants except that the stimulator will be turned off within 30 seconds. As for the s-MT+tDCS group, the participants will receive the same tDCS procedure as the MT+tDCS group while a sham MT condition will be applied. Clinical and neurophysiological assessments will be conducted before the treatment (pretest), after 3 weeks of treatment (post-test), and 1 month after the treatment (follow-up test). The assessments will be performed by research assistants who will be blinded to the group allocation of the participants. Mix-model Group × Time repeated measures ANOVAs will be used to determine the intervention effects of the 3 groups.

Detailed description: Central poststroke pain (CPSP) refers to the symptom of pain arising after a stroke. Patients with CPSP often complain of various painful or unpleasant sensation.The feelings of pain may interfere with sleep and hugely affect the patients' quality of life. Additionally, CPSP may compromise rehabilitation and hinder movement recovery after stroke.

Non-invasive brain stimulation, such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS), is an emerging nonpharmacological treatment and has been shown to have promising pain reduction effects for patients with CPSP. Compared with rTMS, tDCS is less expensive, easier to implement, and requires less labor work. Via a weak current flow, tDCS can modulate neuronal excitability in a polarity-specific manner. Anodal electrode of tDCS can depolarize the membrane potential and enhance corticomotor excitability, while cathodal electrode could reduce neuronal excitability.

Mirror therapy (MT) is a contemporary approach that has often been used to facilitate upper extremity motor recovery in patients with stroke. In addition to motor functions, MT has also been shown to be effective in ameliorating sensory deficits and reducing shoulder pain or reflex sympathetic dystrophy. Despite the evidence on the benefits of MT on sensation and shoulder pain, very few study specifically investigates the effect of MT on CPSP. One single case study reported benefits of MT on CPSP. A larger sample size is warranted to determine whether MT could effectively reduce CPSP. Furthermore, combining MT with non-invasive modulation tool may further intensify sensorimotor reorganization and reduce pain. Therefore, this proposed study aims to determine whether combining MT with tDCS could reduce pain in patients with CPSP.

The goal of this study is to determine the effect of combining MT and tDCS on pain, sensation, motor function, and quality of life in people with CPSP. It is hypothesized that compared with the single treatment groups, combining MT and tDCS will induce greater improvement in pain, motor function, and quality of life in patients with CPSP.

Methods: This study plans to recruit 45 patients with CPSP. The proposed study is designed to be a randomized controlled trial with pretest, posttest, and 1-month follow-up test. After signing the informed consent, eligible participants will be randomly allocated to one of the 3 groups: combining MT with tDCS (MT+tDCS) group, MT with sham tDCS (MT+s-tDCS) group, and sham MT with tDCS (s-MT+tDCS) group.

Clinical and neurophysiological assessments will be conducted before the treatment (pretest), after 3 weeks of treatment (post-test), and 1 month after the treatment (follow-up test). The assessments will be performed by research assistants who will be blinded to the group allocation of the participants.

Throughout the study, all participants will be required to keep their regular treatment regimen, and the current intervention will be an add on treatment for the patients. The participants in all groups will receive intervention 30 minutes/day, 3 days/ week, for 3 weeks resulting in 9 training sessions. The participants in the MT+tDCS group will receive tDCS applied simultaneously with MT for 20 minutes. For the following 10 minutes, the tDCS will be turned off while the electrodes will be kept on the scalp, and the participants will continue with MT. For the MT+s-tDCS group, same tDCS procedures will be applied to the participants except that the stimulator will be turned off within 30 seconds. The participants will perform MT with sham tDCS. As for the s-MT+tDCS group, the participants will receive the same tDCS procedure as the MT+tDCS group while a sham MT condition will be applied.

The outcome measures of this study will include the Mini-Mental Screening Examination (MMSE), subjective pain, pressure pain threshold, Neuropathic pain symptom inventory (NPSI), Quantitative sensory test (QST), Fugl-Mayer Assessment-Upper Extremity (UE-FMA), Box and block test (BBT), Motor activity log (MAL), WHOQOL-BREF Taiwan Version, and Transcranial magnetic stimulation (TMS) assessment, Somatosensory evoked potentials (SSEP), Nerve conduction velocity (NCV). The mix-model Group × Time repeated measures ANOVAs will be used to determine the intervention effects of the 3 groups.

Eligibility criteria: Inclusion Criteria:

* (1) age ranges from 20 to 90 years old,
* (2) history of unilateral ischemic or hemorrhagic stroke for more than 6 months,
* (3) without severe weakness on affected side and able to catch things with affected hand,
* (4) have neuropathic pain and/or sensory deficits occurring in the hemiplegic extremity (Visual Analog Scale ≥ 3), and
* (5) do not have cognitive impairment (Mini-Mental State Examination ≥ 24).

Exclusion Criteria:

* (1) pain caused by reflex sympathetic dystrophy, peripheral neuropathy, structural lesions or due to psychological issues,
* (2) a personal history of seizure or family history of epilepsy,
* (3) metal implanted in the brain,
* (4) implanted pacemaker,
* (5) history of neurological or psychological diseases other than stroke,
* (6) a history of head surgery or brain injury,
* (7) unstable migraine or tinnitus that is not under medication control,
* (8) aphasia,
* (9) pregnancy or breastfeeding,
* (10) poor response to present medication,
* (11) under medication that may influence central nerve system (e.g. reducing threshold of seizure),
* (12) skin sensitive to the application of electrical current,
* (13) sleep deprivation, or
* (14) severe or recent heart diseases.

Primary outcomes:
measure: Change in subjective pain assessed by VAS
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
Secondary outcomes:
measure: Change in Mini-Mental Screening Examination (MMSE)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in pressure pain threshold
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Neuropathic pain symptom inventory (NPSI)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Quantitative sensory test (QST)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Fugl-Mayer Assessment-Upper Extremity (UE-FMA)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Box and block test (BBT)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Motor activity log (MAL)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in WHOQOL-BREF Taiwan Version
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Corticomotor excitability
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Somatosensory evoked potentials (SSEP)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
measure: Change in Nerve conduction velocity (NCV)
timeFrame: 3 time points: before treatment (pre-test), after 3 weeks of treatment (post-test), 1 month after the treatment (follow-up test)
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University
Study officials:
affiliation: National Taiwan University Hospital
name: Sung-Chun Tang, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Taiwan University
name: Ya-Yun Lee, PhD
role: PRINCIPAL_INVESTIGATOR
References: