Dose-finding Study of Selective Serotonin Reuptake Inhibitors to Enhance Neuroplasticity

Sponsor

Burke Medical Research Institute (Other)

Overall Status

Withdrawn

CT.gov ID

NCT04221256

Collaborator

(none)

Enrollment

Location

Arms

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Stroke, Ischemic	Drug: Administration of SSRI escitalopram Behavioral: Paired Associative stimulation Drug: Administration of Placebo	Phase 1/Phase 2

Detailed Description

The brain is able to change throughout life in response to learning, or injury, or to adapt to changes in the environment, which is known as neuroplasticity. Stroke survivors suffer disabling chronic motor impairments that have proven challenging to improve. Increasing neuroplasticity using selective serotonin reuptake inhibitors (SSRIs) is a promising approach to promote motor recovery in patients with stroke. Selective serotonin reuptake inhibitors (SSRIs) are currently widely used for treatment of depression, but they also have been shown to be able to enhance neuroplasticity. A single dose of SSRI has been shown to improve hand function in patients with chronic stroke. SSRIs also enhance neuroplasticity in healthy individuals, as shown using paired associative stimulation (PAS), a non-invasive method which causes the brain's excitability to change. However, the best dose of SSRI to increase neuroplasticity is not yet established.

The purpose of this study is to (1) find the effective dose of the SSRI escitalopram to modulate PAS-induced plasticity in patients with stroke and healthy individuals and (2) determine the variability of escitalopram's effect on PAS-induced plasticity between individuals. We measure neuroplasticity with PAS, which causes the brain's excitability to change. During PAS, you would receive electrical stimulation over your wrist and magnetic stimulation to their scalp (called transcranial magnetic stimulation, or TMS) to increase the excitability of the motor area of the brain. You will be asked to participate in a screening visit and 8 study visits separated by at least 1 week. At each study visit, you will be given a single dose of escitalopram (5, 10 or 20) or placebo, and we will measure your brain's change in excitability after PAS.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

We propose a double-blinded, placebo-controlled crossover study to test a range of doses of escitalopram and a placebo control in enhancing PAS-induced plasticity in healthy individuals without neurological disease and patients with chronic stroke.We propose a double-blinded, placebo-controlled crossover study to test a range of doses of escitalopram and a placebo control in enhancing PAS-induced plasticity in healthy individuals without neurological disease and patients with chronic stroke.

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Dose-finding Study of Selective Serotonin Reuptake Inhibitors to Enhance Neuroplasticity

Actual Study Start Date :

Mar 11, 2020

Actual Primary Completion Date :

Feb 9, 2021

Actual Study Completion Date :

Feb 9, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Administration of SSRI Participants will be administered either 5, 10 or 20mg of SSRI escitalopram prior to paired associative stimulation.	Drug: Administration of SSRI escitalopram Participants will be administered 5, 10 or 20mg of SRRI escitalopram prior to paired associative stimulation Behavioral: Paired Associative stimulation Participants will receive paired associative stimulation (transcranial magnetic stimulation and peripheral nerve stimulation) with an inter-stimulus interval length known to modulate corticospinal excitability.
Placebo Comparator: Administration of Placebo Participants will be administered a placebo prior to paired associative stimulation	Behavioral: Paired Associative stimulation Participants will receive paired associative stimulation (transcranial magnetic stimulation and peripheral nerve stimulation) with an inter-stimulus interval length known to modulate corticospinal excitability. Drug: Administration of Placebo Participants will be administered a placebo prior to paired associative stimulation

Arm

Intervention/Treatment

Experimental: Administration of SSRI

Participants will be administered either 5, 10 or 20mg of SSRI escitalopram prior to paired associative stimulation.

Drug: Administration of SSRI escitalopram

Participants will be administered 5, 10 or 20mg of SRRI escitalopram prior to paired associative stimulation

Behavioral: Paired Associative stimulation

Participants will receive paired associative stimulation (transcranial magnetic stimulation and peripheral nerve stimulation) with an inter-stimulus interval length known to modulate corticospinal excitability.

Placebo Comparator: Administration of Placebo

Participants will be administered a placebo prior to paired associative stimulation

Behavioral: Paired Associative stimulation

Drug: Administration of Placebo

Participants will be administered a placebo prior to paired associative stimulation

Outcome Measures

Primary Outcome Measures

Change in motor evoked potential amplitude [Baseline, Up to 30 minutes Post PAS]
Assessment of corticospinal excitability

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Neurological Healthy Participants Inclusion criteria

Men and women aged 18 years and older.
Ability to give informed consent.

Exclusion criteria

Contraindications to TMS: epilepsy or other seizure history, ferromagnetic metallic implants in the head, or pacemaker
Current or history of neurological disorders or brain lesions such as stroke, multiple sclerosis, tumor, traumatic brain injury, spinal cord injury
Diagnosis of major depressive disorder or other psychiatric disorder
Currently taking escitalopram or another selective serotonin reuptake inhibitor
Currently taking or have taken in the past month other medications or supplements that have known interactions with escitalopram or can precipitate serotonin syndrome when taken in combination with escitalopram: monoamine oxidase inhibitors, methylene blue, linezolid, serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants (TCAs), fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's wort
Known hypersensitivity to escitalopram or any of its inactive ingredients.
History of cerebral hemorrhage, gastrointestinal bleeding, or genitourinary bleeding.
History of prolonged QTc
Pregnant or breastfeeding
Social and/or personal circumstances that interfere with the ability to return for all study visits.

Stroke Patients Inclusion criteria

Men and women aged 18 years and older.
Ability to give informed consent.
History of ischemic stroke

Exclusion criteria

Contraindications to TMS: epilepsy or other seizure history, ferromagnetic metallic implants in the head, or pacemaker
Current or history of neurological disorders or brain lesions such as multiple sclerosis, tumor, traumatic brain injury, spinal cord injury
Diagnosis of major depressive disorder or other psychiatric disorder
Currently taking escitalopram or another selective serotonin reuptake inhibitor
Currently taking or have taken in the past month other medications or supplements that have known interactions with escitalopram or can precipitate serotonin syndrome when taken in combination with escitalopram: monoamine oxidase inhibitors, methylene blue, linezolid, serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants (TCAs), fentanyl, lithium, tramadol, tryptophan, buspirone, amphetamines, St. John's wort
Known hypersensitivity to escitalopram or any of its inactive ingredients.
History of cerebral hemorrhage, gastrointestinal bleeding, or genitourinary bleeding.
History of prolonged QTc
Pregnant or breastfeeding
Social and/or personal circumstances that interfere with the ability to return for all study visits.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Burke Neurological Institute	White Plains	New York	United States	10605

Sponsors and Collaborators

Burke Medical Research Institute

Investigators

Principal Investigator: Tomoko Kitago, MD, Winifred Masterson Burke Medical Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Tomoko Kitago, Lab Director Human Motor Recovery Laboratory Assistant Professor, Burke Medical Research Institute

ClinicalTrials.gov Identifier:

NCT04221256

Other Study ID Numbers:

HMRL-002

First Posted:

Jan 9, 2020

Last Update Posted:

Jul 23, 2021

Last Verified:

Jul 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Tomoko Kitago, Lab Director Human Motor Recovery Laboratory Assistant Professor, Burke Medical Research Institute

Selective Serotonin Reuptake Inhibitor

Neuroplasticity

Paired Associative Stimulation

Additional relevant MeSH terms:

Ischemic Stroke

Citalopram

Study Results

No Results Posted as of Jul 23, 2021