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

NCT ID: NCT04221256

Last Updated: 2021-07-23

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE1/PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-11
• Study Completion Date: 2021-02-09

Brief Summary

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.

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.

Conditions

Stroke, Ischemic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Administration of SSRI

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

Group Type: EXPERIMENTAL

Administration of SSRI escitalopram

Intervention Type: DRUG

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

Paired Associative stimulation

Intervention Type: BEHAVIORAL

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

Administration of Placebo

Participants will be administered a placebo prior to paired associative stimulation

Group Type: PLACEBO_COMPARATOR

Paired Associative stimulation

Intervention Type: BEHAVIORAL

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

Administration of Placebo

Intervention Type: DRUG

Participants will be administered a placebo prior to paired associative stimulation

Interventions

Administration of SSRI escitalopram

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

Intervention Type: DRUG

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.

Intervention Type: BEHAVIORAL

Administration of Placebo

Participants will be administered a placebo prior to paired associative stimulation

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Men and women aged 18 years and older.

2. Ability to give informed consent.

1. Men and women aged 18 years and older.

2. Ability to give informed consent.

3. History of ischemic stroke

Exclusion Criteria

1. Contraindications to TMS: epilepsy or other seizure history, ferromagnetic metallic implants in the head, or pacemaker

2. Current or history of neurological disorders or brain lesions such as stroke, multiple sclerosis, tumor, traumatic brain injury, spinal cord injury

3. Diagnosis of major depressive disorder or other psychiatric disorder

4. Currently taking escitalopram or another selective serotonin reuptake inhibitor

5. 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

6. Known hypersensitivity to escitalopram or any of its inactive ingredients.

7. History of cerebral hemorrhage, gastrointestinal bleeding, or genitourinary bleeding.

8. History of prolonged QTc

9. Pregnant or breastfeeding

10. Social and/or personal circumstances that interfere with the ability to return for all study visits.

1. Contraindications to TMS: epilepsy or other seizure history, ferromagnetic metallic implants in the head, or pacemaker

2. Current or history of neurological disorders or brain lesions such as multiple sclerosis, tumor, traumatic brain injury, spinal cord injury

3. Diagnosis of major depressive disorder or other psychiatric disorder

4. Currently taking escitalopram or another selective serotonin reuptake inhibitor

5. 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

6. Known hypersensitivity to escitalopram or any of its inactive ingredients.

7. History of cerebral hemorrhage, gastrointestinal bleeding, or genitourinary bleeding.

8. History of prolonged QTc

9. Pregnant or breastfeeding

10. Social and/or personal circumstances that interfere with the ability to return for all study visits.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Burke Medical Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Tomoko Kitago

Lab Director Human Motor Recovery Laboratory Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tomoko Kitago, MD

Role: PRINCIPAL_INVESTIGATOR

Winifred Masterson Burke Medical Research Institute

Locations

Burke Neurological Institute

White Plains, New York, United States

Countries

United States

Other Identifiers

HMRL-002

Identifier Type: -

Identifier Source: org_study_id