COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC:

Get the latest research information from NIH: Menu
Trial record 1 of 518 for:    ESCITALOPRAM AND Serotonin Uptake
Previous Study | Return to List | Next Study

Cortical Ischemic Stroke and Serotonin (CISS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02865642
Recruitment Status : Recruiting
First Posted : August 12, 2016
Last Update Posted : March 6, 2020
Cantonal Hospital of St. Gallen
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Tracking Information
First Submitted Date  ICMJE August 4, 2016
First Posted Date  ICMJE August 12, 2016
Last Update Posted Date March 6, 2020
Study Start Date  ICMJE August 2016
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 9, 2016)
Effect of escitalopram on sensorimotor network [ Time Frame: fMRI at month 9 ]
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
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2016)
  • Imaging patterns of rs-fMRI [ Time Frame: rs-fMRI (baseline, month 3, month 9) ]
    To compare imaging patterns of rs-fMRI and associated behavioral parameters of the verum and placebo group with those of healthy volunteers in the longterm in order to assess the degree of recovery.
  • Imaging patterns of act-fMRI [ Time Frame: act-fMRI, performance of tactile manipulation of objects (baseline, month 3, month 9) ]
    To compare imaging patterns act-fMRI and associated behavioral parameters of the verum and placebo group with those of healthy volunteers in the longterm from baseline until month 3 and 9 in order to assess the degree of recovery and the associated efficiency in performing tactile manipulation of objects.
  • Jebsen-Taylor Test (JTT) [ Time Frame: JTT, monthly from baseline to month 9 ]
    To calculate the recovery trajectories of subjects post-stroke, relying on motor subtests of the JTT which will be carried out monthly from baseline to month 9.
  • Mean cortical volume changes [ Time Frame: T1 from baseline, month 3, month 9 ]
    To delineate overall mean cortical volume changes in the longterm from baseline until 9 months in high-resolution T1-images to detect structural reorganization post-stroke both perilesional and in distributed large scale networks specifically related to hand motor skill in the verum and placebo group.
  • Serum concentration of escitalopram [ Time Frame: Serum concentration at month 3 ]
    To explore the serum concentration (µg/L) of escitalopram as possibly confounding factors impacting on the study results.
  • Genetic polymorphisms in genes [ Time Frame: Genetic polymorphisms in genes at month 3 ]
    To explore the number of patients with genetic polymorphisms in genes (CYP2P19, ABCB1, CYP3A4 or CYP3A5) as possibly confounding factors impacting on the study results.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: August 9, 2016)
  • Glutamate/Glutamine concentration [ Time Frame: Spectroscopy at baseline, month 3, month 9 ]
    Substudy Center 1: To measure Glutamate/Glutamine concentration post-stroke by MR-Spectroscopy in predefined brain areas (i.e. in the ipsilesional sensorimotor cortex and dorsolateral prefrontal cortex) as possible factor interfering with the recovery process
  • rTMS [ Time Frame: TMS at baseline, month 3, month 9 ]
    Substudy Center 2: To assess for facilitation in the motor system after application of escitalopram, using rTMS in the verum group related to the placebo group.
  • Number of adverse events due to study medication [ Time Frame: Baseline, monthly until month 9 ]
    Number of adverse events due to study medication Safety Endpoint: Experiencing at least one serious adverse event (e.g. death, life-threatening, requires inpatient hospitalization)
Original Other Pre-specified Outcome Measures Same as current
Descriptive Information
Brief Title  ICMJE Cortical Ischemic Stroke and Serotonin
Official Title  ICMJE CISS: Cortical Ischemic Stroke and Serotonin - Effects of Serotonergic Neuromodulation on Behavioural Recovery and Motor Network Plasticity After Cortical Ischemic Stroke: a Longitudinal, Placebo-controlled Study
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.
Detailed Description

Neuroplasticity, i.e. the human brain's innate capacity to structurally remodel and functionally reorganize its neural networks, is essential for recovery of impaired sensorimotor function after focal ischemic injury. However, the potential for spontaneous recovery in the adult brain is limited and needs to be augmented through rehabilitative programs, e.g. intensive exercise, brain stimulation or pharmacologic neuromodulation.

Clinical studies have shown that post-stroke recovery can be augmented by long-term administration of selective serotonin reuptake inhibitors (SSRI). Serotonin modulates excitatory glutamatergic neurotransmission and induces long-term potentiation (LTP), an important mediator of neuroplasticity that supports sensorimotor learning in the healthy brain and reorganization in the post-stroke perilesional cortex. Preliminary data indicate that a single dose of the SSRI Escitalopram is sufficient to induce LTP-like effects in the motor cortex of healthy volunteers (measured by repetitive transcranial magnetic stimulation (rTMS)), and to increase the efficiency of large-scale functional connectivity networks engaged in tactile object manipulation ( measured with functional magnetic resonance imaging (fMRI)).

The investigators thus hypothesize that serotonergic neuromodulation might enhance post-stroke recovery through enlarged plasticity and processing efficiency along integrated neuronal networks, leading to reinforced connectivity and behavioural performance.

To test this hypothesis, the investigators aim to conduct a longitudinal, double blind, placebo-controlled trial in two neurological centers. The investigators aim to test the effect of a daily-administered single dose of Escitalopram over a three months period after cortical ischemic stroke to promote plasticity changes in the perilesional zone of primary sensorimotor cortices (S1 and M1). The investigators will apply behavioural measures of hand function, rTMS and advanced magnetic resonance (MR) imaging techniques as outcome variables.

The investigators will measure hand function kinematics with a data glove to better understand the contribution of effort to hand function recovery and brain activation. Moreover, the investigators intend to apply MR-Spectroscopy of the perilesional premotor cortex, guided by real-time fMRI analysis, as a tool to assess local glutamatergic transmission. Measurements of plasma drug levels and determination of genetic polymorphisms of the Escitalopram-metabolizing genes will help them to assess and control for interindividual variance in Escitalopram bioavailability.

The investigators expect that SSRI-augmented neuroplasticity will lead to increased efficiency in the allocation of neuronal resources in the post-stroke brain, resulting in more precise and less effortful movements, facilitation of LTP-like phenomena, increased grey matter volume of spared perilesional premotor cortex and possibly higher glutamate peaks in the same areas, as compared to placebo treatment.

By combining standard and innovative methods, this study will provide mechanistic insight into the processes that drive cortical neuroplasticity in the post-stroke human brain. From a clinical perspective, results from the study are expected to provide a scientific rationale to select patients that might benefit from SSRI-augmented neurorehabilitation.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Supportive Care
Condition  ICMJE Stroke
Intervention  ICMJE
  • Drug: Serotonin Uptake Inhibitors
    Other Name: Escitalopram, Cipralex
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: Serotonin Uptake Inhibitors

    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.

    Intervention: Drug: Serotonin Uptake Inhibitors
  • Placebo Comparator: Placebo

    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.

    Intervention: Drug: Placebo
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 10, 2017)
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2016)
Estimated Study Completion Date  ICMJE December 2020
Estimated Primary Completion Date September 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • No pregnancy
  • Written informed consent
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Manuela Pastore-Wapp +41316320006
Contact: Werner Krammer
Listed Location Countries  ICMJE Switzerland
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT02865642
Other Study ID Numbers  ICMJE 3070
2016-00417 ( Other Identifier: KEK )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party University Hospital Inselspital, Berne
Study Sponsor  ICMJE University Hospital Inselspital, Berne
Collaborators  ICMJE Cantonal Hospital of St. Gallen
Investigators  ICMJE
Principal Investigator: 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
PRS Account University Hospital Inselspital, Berne
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP