SSRIs and TDCS Enhance Post-stroke Motor Recovery

Combining SSRIs and TDCS to Enhance Motor Recovery After Stroke

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke; Motor
• Intervention / Treatment: Device: tDCS; Drug: Citalopram; Behavioral: Rehabilitation

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 Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real tDCS + Citalopram + 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	Device: tDCS; dual tDCS with ipsilesional primary motor cortex (M1) anodal stimulation and contralesional M1 cathodal stimulation, 2 weeks after SSRI treatment; Drug: Citalopram; total 3 months, since 2-4 weeks after stroke; Behavioral: Rehabilitation; hospitalized rehabilitation, 3 hours daily
Sham Comparator: Sham tDCS + Citalopram + 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	Drug: Citalopram; total 3 months, since 2-4 weeks after stroke; Behavioral: Rehabilitation; hospitalized rehabilitation, 3 hours daily
Placebo Comparator: Real tDCS + Placebo + 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	Device: tDCS; dual tDCS with ipsilesional primary motor cortex (M1) anodal stimulation and contralesional M1 cathodal stimulation, 2 weeks after SSRI treatment; Behavioral: Rehabilitation; hospitalized rehabilitation, 3 hours daily
Placebo Comparator: Sham tDCS + Placebo + 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	Behavioral: Rehabilitation; hospitalized rehabilitation, 3 hours daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor scores 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)	3 months after intervention

Collaborators and Investigators

• Sponsor: Chih-Wei Tang
• Collaborators: University of Oxford; Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2021
• Primary Completion (Anticipated): August 31, 2024
• Study Completion (Anticipated): August 31, 2025

Study Registration Dates

• First Submitted: September 2, 2021
• First Submitted That Met QC Criteria: September 10, 2021
• First Posted (Actual): September 13, 2021

Study Record Updates

• Last Update Posted (Actual): September 13, 2021
• Last Update Submitted That Met QC Criteria: September 10, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: stroke, motor recovery, transcranial direct current stimulation, selective serotonin reuptake inhibitors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Antidepressive Agents, Second-Generation; Citalopram
• Other Study ID Numbers: Co-STARS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No