SSRIs and TDCS Enhance Post-stroke Motor Recovery

Phase 3

Not yet recruiting

• Conditions: Stroke; Motor
• Interventions: Device: tDCS; Behavioral: Rehabilitation; Drug: Citalopram

• Registration Number: NCT05041582
• Lead Sponsor: Chih-Wei Tang

Brief Summary

Post-stroke motor recovery is compelling but limited. Current rehabilitation has less impacts on the plateau that spontaneous biological recovery could be expected. The advances in non-invasive neuromodulation and neurophysiological characterization of critical motor recovery period enable breaking the proportional recovery limitation. Our pilot studies demonstrated the safety and responsiveness of combing dual transcranial direct current stimulation (tDCS) and motor training in subacute stroke patients. There is also strong evidence that selective serotonin reuptake inhibitors (SSRIs) can substantially increase the effects of tDCS and improve motor function after stroke, even in the absence of depression. This proposal aims to prove the potential of combining of tDCS and the commonly used SSRI citalopram to improve response to a daily motor training intervention in acute stroke patients (Co-STARS trial).

Detailed Description

This is a randomized, double-blind, sham-controlled study in 80 patients with first-ever, unilateral, subcortical ischemic stroke 0.5-4 weeks after stroke onset with moderate to severe hemiparesis. Participants were randomized into four groups underwent either real dual tDCS \[ipsilesional primary motor cortex (M1) anodal stimulation and contralesional M1 cathodal stimulation; 2 mA for 20 mins; 10 sessions within 2 weeks\] with citalopram or placebo, or sham stimulation with citalopram or placebo. All will receive concurrent hospitalized intensive rehabilitation of 2 daily sessions of 90-minute physiotherapy. Action reach am test (ARAT), Fugl-Meyer Assessment (FMA), multimodality MRI and EEG will be measured at baseline and after 2 weeks' tDCS modulation. The primary outcome is the ARAT at 3 months after intervention. The combination of tDCS and a SSRI will be expected to improve response to motor training more effectively than either intervention alone. The enhanced responsiveness will be correlated or predicted by biomarkers from multimodality MRI or EEG.

Study Timeline

• Status Verified: 2021-09
• Study Start: 2021-09-01
• Study First Submitted: 2021-09-02
• Study First Submitted QC: 2021-09-10
• Last Update Submitted: 2021-09-10
• Study First Posted: 2021-09-13
• Last Update Posted: 2021-09-13
• Primary Completion: 2024-08-31
• Study Completion: 2025-08-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• aged 20-80;
• first-onset stroke
• brain image confirmed unilateral subcortical infarction
• moderate to severe upper-limb impairment (SAFE score <8).
• 3 days to 4 weeks after stroke onset
• stable medical condition

Exclusion Criteria

• metal implants, such as electrodes or pacemaker
• epilepsy history or active spikes from EEG recording
• major depression or taking psychoactive drugs
• alcoholism or drug abuse history
• combined with other severe neurological or psychiatric diagnoses
• pregnancy or breastfeeding;
• other contraindications to brain MRI, such as severe claustrophobia
• intolerance to electrical stimulation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Real tDCS + Placebo + Rehabilitation	tDCS	* Real tDCS, 2 mA for 20 mins per session, 10 sessions within 2 weeks * Placebo oral intake daily for 3 months, since 2 weeks before tDCS
Real tDCS + Citalopram + Rehabilitation	tDCS	* Real tDCS, 2 mA for 20 mins per session, 10 sessions within 2 weeks * Citalopram 10mg oral intake daily for 3 months, since 2 weeks before tDCS
Sham tDCS + Citalopram + Rehabilitation	Rehabilitation	* Sham tDCS, ramped up over 10 seconds and then reduced to 0mA, 10 sessions within 2 weeks * Citalopram 10mg oral intake daily for 3 months, since 2 weeks before tDCS
Real tDCS + Citalopram + Rehabilitation	Rehabilitation	* Real tDCS, 2 mA for 20 mins per session, 10 sessions within 2 weeks * Citalopram 10mg oral intake daily for 3 months, since 2 weeks before tDCS
Real tDCS + Placebo + Rehabilitation	Rehabilitation	* Real tDCS, 2 mA for 20 mins per session, 10 sessions within 2 weeks * Placebo oral intake daily for 3 months, since 2 weeks before tDCS
Sham tDCS + Placebo + Rehabilitation	Rehabilitation	* Sham tDCS, ramped up over 10 seconds and then reduced to 0mA, 10 sessions within 2 weeks * Placebo oral intake daily for 3 months, since 2 weeks before tDCS
Real tDCS + Citalopram + Rehabilitation	Citalopram	* Real tDCS, 2 mA for 20 mins per session, 10 sessions within 2 weeks * Citalopram 10mg oral intake daily for 3 months, since 2 weeks before tDCS
Sham tDCS + Citalopram + Rehabilitation	Citalopram	* Sham tDCS, ramped up over 10 seconds and then reduced to 0mA, 10 sessions within 2 weeks * Citalopram 10mg oral intake daily for 3 months, since 2 weeks before tDCS

Primary Outcome Measures

Name	Time	Method
Motor scores 3 months after intervention	3 months after intervention	Motor scores include Action research arm test (0-66, higher scores mean a better outcome) and Fugl-Meyer Assessment (0-54, higher scores mean a better outcome)