Cortical Ischemic Stroke and Serotonin

NCT02865642 | Unknown Phase 2 DMC

• 2 other identifiers: 30702016-00417
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 2

Brief Summary

In this study the investigators want to test the hypotheses that, serotonergic neuromodulation increases perilesional neuroplasticity, leading to improved behavioural outcomes through a more efficient allocation of functional resources, greater structural reorganization and less remapping via alternative circuits.

Conditions

Stroke

Keywords

Stroke; Serotonin; Hand Paresis

Outcome Measures

Primary Outcomes (1)

• Effect of escitalopram on sensorimotor network

  To verify higher expression of the sensorimotor network engaged in motor control in the blood oxygenation level dependent (BOLD) response of task-related fMRI (act-fMRI) in patients treated with escitalopram compared to patients treated with placebo after nine months

  fMRI at month 9

Secondary Outcomes (6)

• Imaging patterns of rs-fMRI

  rs-fMRI (baseline, month 3, month 9)

• Imaging patterns of act-fMRI

  act-fMRI, performance of tactile manipulation of objects (baseline, month 3, month 9)

• Jebsen-Taylor Test (JTT)

  JTT, monthly from baseline to month 9

• Mean cortical volume changes

  T1 from baseline, month 3, month 9

• Serum concentration of escitalopram

  Serum concentration at month 3

Other Outcomes (3)

• Glutamate/Glutamine concentration

  Spectroscopy at baseline, month 3, month 9

• rTMS

  TMS at baseline, month 3, month 9

• Number of adverse events due to study medication

  Baseline, monthly until month 9

Study Arms (2)

Serotonin Uptake Inhibitors

EXPERIMENTAL

Treatment 1: Starting with Escitalopram 5mg/day at the baseline-visit (day 14 (+-7) post stroke) for 7 days followed by a weekly dosage increase of 5mg/day till target dose of Escitalopram 20mg/day. Subjects will remain on Escitalopram 20mg/day until visit 3 (day 90 (+-14) post stroke) followed by dosage reduction of Escitalopram 10mg/day for one week.

Drug: Serotonin Uptake Inhibitors

Placebo

PLACEBO COMPARATOR

Treatment 2: Starting with Placebo 5mg/day at the baseline-visit (day 14 (+-7) post stroke) for 7 days followed by a weekly dosage of 5mg/day till target dose of Placebo 20mg/day. Subjects will remain on Placebo 20mg/day until visit 3 (day 90 (+-14) post stroke) followed by Placebo 10mg/day for one week.

Drug: Placebo

Interventions

Serotonin Uptake Inhibitors DRUG

Also known as: Escitalopram, Cipralex

Serotonin Uptake Inhibitors

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• First-ever stroke
• Clinically significant contralesional hand plegia or paresis as a main symptom
• Involvement of the pre-and/or postcentral gyri confirmed on diffusion-weighted (DWI) and fluid attenuated inversion recovery (FLAIR) scans.
• Written informed consent

You may not qualify if:

• Aphasia or cognitive deficits severe enough to preclude understanding of study purposes
• Prior cerebrovascular events
• Significant stenosis (70-99% according to NASCET) or occlusion of the carotid and intracranial arteries on MR-angiography
• 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 or suspected hypersensitivity (allergic) to one of the ingredients of Cipralex® or Placebo
• Simultaneous administration of: antidepressants, irreversible non- selective Monoamine Oxidase (MAO) inhibitors, reversible selective MAO inhibitors, reversible non-selective MAO inhibitors, irreversible selective MAO inhibitors, N-methyl-D-aspartate(NMDA)-receptor antagonists/-agonists, dopamine antagonists/-agonists, levodopa, benzodiazepines, amphetamines, methylphenidate, foscarnet, ganciclovir, ritonavir, mianserin, chloroquine, mefloquine, imipenem, penicillin, ampicillin, cephalosporins, metronidazole, isoniazid, levofloxacin, cyclosporin, chlorambucil, vincristine, methotrexate, cytosine arabinoside, lithium, anticholinergics,systemic antihistamines, systemic sympathomimetics
• Conditions interfering with MRI such as patients with magnetic (metallic) particles in the scull or brain, patients with a cardiac pacemaker, deep brain stimulators or cochlear implant.
• Women who are pregnant or breastfeeding
• Women in childbearing age without sufficient birth control (at least 2 contraceptive methods)
• Eligibility Criteria for healthy volunteers:
• Normal test-scores at the baseline visit (see section 5.2.2)
• Normal neurological status
• No known brain lesion

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• Cantonal Hospital of St. Gallen: collaborator

Study Sites (2)

Neurology Department Kantonsspital St. Gallen

Sankt Gallen, Canton of St. Gallen, 9007, Switzerland

NOT YET RECRUITING

Support Center of Advanced Neuroimaging Institute for Diagnostic and Interventional Neuroradiology Inselspital, University Hospital Bern

Bern, 3010, Switzerland

RECRUITING

Related Publications (1)

• Krammer W, Missimer JH, Habegger S, Pastore-Wapp M, Wiest R, Weder BJ. Sensing form - finger gaiting as key to tactile object exploration - a data glove analysis of a prototypical daily task. J Neuroeng Rehabil. 2020 Oct 8;17(1):133. doi: 10.1186/s12984-020-00755-6.

  PMID: 33032615 DERIVED

MeSH Terms

Conditions

Stroke

Interventions

Selective Serotonin Reuptake Inhibitors; Escitalopram; Dexetimide

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Neurotransmitter Agents; Serotonin Agents; Physiological Effects of Drugs; Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring

Study Officials

• Roland Wiest

  Support Center of Advanced Neuroimaging Institute for Diagnostic and Interventional Neuroradiology Inselspital, University Hospital Bern

  PRINCIPAL INVESTIGATOR

• Georg Kägi

  Neurology Department Kantonsspital St. Gallen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Manuela Pastore-Wapp

CONTACT

+41316320006; manuela.pastore-wapp@insel.ch

Werner Krammer

CONTACT

werner.krammer@kssg.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2016
• First Posted: August 12, 2016
• Study Start: August 1, 2016
• Primary Completion: September 1, 2020
• Study Completion: December 1, 2020
• Last Updated: March 6, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

CH (2)