Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Enhancement of Learning Associated Neural Plasticity by Selective Serotonin Reuptake Inhibitors

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02753738
Recruitment Status : Unknown
Verified April 2016 by Rupert Lanzenberger, Medical University of Vienna.
Recruitment status was:  Not yet recruiting
First Posted : April 28, 2016
Last Update Posted : April 28, 2016
Sponsor:
Information provided by (Responsible Party):
Rupert Lanzenberger, Medical University of Vienna

Brief Summary:

Background:

Conclusive evidence states that the serotonergic system mediates neuroplasticity from early embryonic development until brain maturation in adulthood. This study aims to demonstrate that selective serotonin reuptake inhibitors (SSRIs) enhance learning-dependent neuroplasticity in vivo, hereby contributing to the investigators understanding of the mechanism of action of therapy with SSRIs.

Objectives:

  1. To prove a positive influence of SSRIs on structural remodeling during learning, reflected by enhancements of gray and white matter microstructure, connectivity and functionality in brain regions involved in learning processes.
  2. To show that this effect is topologically specific, i.e. that enhancements of plasticity markers are found in different regions depending on their involvement during the performance of specific learning tasks.

Study design:

Randomized, double-blind, placebo-controlled, longitudinal mono-center study. 80 healthy subjects will undergo three MRI scanning sessions: 1. baseline, at study entry, 2. after 3 weeks of facial/emotional (n=40) or Chinese character-meaning learning (n=40) and 3. after 3 weeks learning of new associations under administration of an SSRI or placebo.

Methods:

MRI measurements will be performed on a 3 Tesla PRISMA MAGNETOM MR scanner. Changes in gray matter microstructure will be assessed using high-resolution structural MRI and analyzed with voxel-based morphometry (VBM). Diffusion tensor imaging (DTI) enables non-invasive investigation of neuroplasticity in the human brain based on the reduction in mean diffusivity associated with swelling of astrocytes after increased synaptic activity. Resting-state functional MRI (fMRI) will allow for the measurement of changes in functional coupling between brain regions, and fMRI during tasks will assess differential activity in brain regions during learning.

Relevance and implications:

This study aims to provide evidence that SSRIs facilitate cytoarchitectonical restructuring. In addition to expanding the investigators current knowledge on the trophic effects of SSRIs, the results of this study will also elucidate interactions between the serotonergic system and changes to neuronal networks during learning as well as their behavioral consequences. By probing the neurobiological correlates of the antidepressant and anti-anxiety effects of SSRIs, this study will provide a rationale for targeted interventions that harness the neuroplasticity enhancing properties of SSRIs to facilitate therapeutic processes.


Condition or disease Intervention/treatment Phase
Ssri Neuronal Plasticity Drug: Escitalopram Drug: Placebo Other: 3xMR scan (fMRI, DTI, strucutral MRI) Behavioral: Association learning paradigm Behavioral: Association re-learning paradigm Phase 4

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Official Title: Enhancement of Learning Associated Neural Plasticity by Selective Serotonin Reuptake Inhibitors
Study Start Date : August 2016
Estimated Primary Completion Date : August 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Serotonin

Arm Intervention/treatment
Experimental: SSRI treatment
Subjects will receive 21 days of 10mg escitalopram treatment while performing learning paradigms.
Drug: Escitalopram
Tablet 10mg, 21 days

Other: 3xMR scan (fMRI, DTI, strucutral MRI)
3 Tesla PRISMA MAGNETOM MR scanner; performed at baseline, after 21 days of performing learning paradigms and after 21 days of drug/placebo treatment and re-learning paradigms

Behavioral: Association learning paradigm
21 daily internet-based sessions (20min) of learning associations (pairs) of stimuli

Behavioral: Association re-learning paradigm
21 daily internet-based sessions (20min) of learning new associations (pairs) of stimuli performed during escitalopram/placebo treatment

Placebo Comparator: Placebo treatment
Subjects will receive 21 days of placebo treatment while performing learning paradigms.
Drug: Placebo
Tablet, 21 days

Other: 3xMR scan (fMRI, DTI, strucutral MRI)
3 Tesla PRISMA MAGNETOM MR scanner; performed at baseline, after 21 days of performing learning paradigms and after 21 days of drug/placebo treatment and re-learning paradigms

Behavioral: Association learning paradigm
21 daily internet-based sessions (20min) of learning associations (pairs) of stimuli

Behavioral: Association re-learning paradigm
21 daily internet-based sessions (20min) of learning new associations (pairs) of stimuli performed during escitalopram/placebo treatment




Primary Outcome Measures :
  1. Gray matter volume [ Time Frame: 21 days ]
    voxel based morphometry (T1 weighted MPRAGE sequence)

  2. Mean diffusivity [ Time Frame: 21 days ]
    diffusion tensor imaging


Secondary Outcome Measures :
  1. BOLD signal [ Time Frame: 21 days ]
    functional MRI (learning paradigms)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • General health based on medical history, physical examination and structured clinical interview for DSM-IV (SCID)
  • Willingness and competence to sign the informed consent form
  • Right-handedness
  • Non-smoker, and non-alcohol drinker

Exclusion Criteria:

  • Any medical, psychiatric or neurological illness
  • Current or former substance abuse
  • Any implant or stainless steel graft or any other contraindications for MRI
  • First degree relatives with a history of psychiatric illness or substance abuse
  • Color blindness, any Chinese language skills
  • Failure to comply with the study protocol or to follow the instructions of the investigating team
  • Lifetime use of SSRIs or related psychotropic agents
  • Non-Caucasian

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02753738


Locations
Layout table for location information
Austria
Department of Psychiatry and Psychotherapy, Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna

Layout table for additonal information
Responsible Party: Rupert Lanzenberger, Prof MD, Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02753738     History of Changes
Other Study ID Numbers: 21042016
First Posted: April 28, 2016    Key Record Dates
Last Update Posted: April 28, 2016
Last Verified: April 2016
Additional relevant MeSH terms:
Layout table for MeSH terms
Dexetimide
Citalopram
Serotonin Uptake Inhibitors
Serotonin
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Serotonin Receptor Agonists