Pastore‐Wapp 2016.

Trial name or title	Cortical Ischemic Stroke and Serotonin (CISS)
Methods	Study type: interventional (clinical trial) Estimated enrolment: 90 participants Allocation: randomised Intervention model: parallel assignment Masking: quadruple (participant, care provider, investigator, outcomes assessor) Primary purpose: supportive care
Participants	Country: Switzerland Setting: inpatient Inclusion criteria: First‐ever stroke Clinically significant contralesional hand plegia or paresis as a main symptom Involvement of the pre‐and/or post‐central gyri confirmed on DWI and FLAIR scans Written informed consent Exclusion criteria: Aphasia or cognitive deficits severe enough to preclude understanding of study purposes Prior cerebrovascular events Significant stenosis (70% to 99% according to NASCET) or occlusion of the carotid and intracranial arteries on MRA Purely subcortical stroke Known brain lesion (tumour, old cerebral haemorrhage) Other medical conditions interfering with task performance or SSRI‐treatment, specifically: prolonged corrected QT interval (QTc) on electrocardiogram, ongoing drug/alcohol abuse Simultaneous intake of medications which can lead to prolonged QTc syndrome known or suspected hypersensitivity to one of the ingredients of Cipralex® or placebo Simultaneous administration of antidepressants Conditions interfering with MRI (e.g. patients with a cardiac pacemaker or cochlear implant) Pregnant or breastfeeding Women in childbearing age without sufficient birth control (at least 2 contraceptive methods)
Interventions	Experimental: escitalopram 5 mg/day at the baseline visit (day 14 (±7) post‐stroke) for 7 days followed by a weekly dosage increase of 5 mg/day till target dose of escitalopram 20 mg/day. Participants remain on escitalopram 20 mg/day until visit 3 (day 90 (±14) post‐stroke) followed by dosage reduction of escitalopram 10 mg/day for 1 week Comparator: placebo 5 mg/day at the baseline visit (day 14 (±7) post‐stroke) for 7 days followed by a weekly dosage of 5 mg/day until target dose of placebo 20 mg/day. Participants remain on placebo 20 mg/day until visit 3 (day 90 (±14) post‐stroke) followed by placebo 10 mg/day for 1 week
Outcomes	Primary outcome Effect of escitalopram on sensorimotor network at month 9 (task‐related fMRI (act‐fMRI)) Secondary outcomes: Imaging patterns of rs‐fMRI at month 3 and month 9 Imaging patterns of act‐fMRI at month 3 and month 9 JTT monthly from baseline to month 9 Mean cortical volume changes at month 3 and month 9 Serum concentration of escitalopram at month 3 Genetic polymorphisms in genes at month 3 Other outcomes: Glutamate/glutamine concentration at month 3 and month 9 rTMS at month 3 and month 9 Number of adverse events due to study medication monthly until month 9
Starting date	August 2016
Contact information	Manuela Pastore‐Wapp manuela.pastore‐wapp@insel.ch
Notes	NCT02865642