Use of Transmucosal Ketamine in Post Stroke Depression

Studies have shown that ketamine is very effective and has a quick onset in treatment of depression. Most of these studies used intravenous ketamine in an inpatient setting and there are no large trials examining its use in Post Stroke Depression (PSD). There have been only few studies that have used other routes of administration (i.e., oral, transmucosal, intranasal, intramuscular) of ketamine which provided symptom relief for depression. The purpose of this study is to assess the effectiveness and safety of use of transmucosal ketamine in treatment of PSD. We hypothesize that fast acting antidepressant effects can be achieved with tolerable side effects for translation into the general post-stroke population. To test our hypothesis, the specific aim is to: (1) demonstrate that transmucosal administration of ketamine is feasible within the post-stroke depression population and has tolerable side effects. Exploratory aims will include assessment if ketamine also produces fast acting antidepressant effects.

Study Overview

• Status: Recruiting
• Conditions: Post-stroke Depression
• Intervention / Treatment: Drug: Ketamine

• Study Type: Interventional
• Enrollment (Anticipated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amelia Adcock; Phone Number: (304) 293-3527; Email: akadcock@hsc.wvu.edu

Study Locations

• United States
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • WVU Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Men and women (18 years of age or older) of any ethnicity diagnosed with Major Depressive Disorder (DSM-V criteria), who have had failed to respond to prior therapy (as defined as at least one anti-depressant trial or patient was intolerant or noncompliant with anti-depressive medications).
• Willing to take the study drug ketamine on 2 separate occasions and comply with instructions for testing.
• Understands and willing to undergo risks associated with adverse effects of study medications.
• Willing to comply with restrictions and instructions disclosed in the consent form.

Exclusion Criteria:

• Patients with blood pressure over 150 systolic or heart rate over 110 on day of medication administration
• Patients with a diagnosis of epilepsy
• Patients with a significant history of high intraocular pressure.
• Patients with life threatening medical problems.
• Participant is pregnant or breastfeeding.
• Infants and children
• Patients who lack medical decision-making capacity
• Patients who would require medication adjustment during time in the study.
• Known hypersensitivity to the study drug (ketamine).
• Unwilling to undergo risks associated with adverse effects of study drugs.
• Unwilling to comply with restrictions and instructions disclosed in the consent form

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Ketamine dose; The recommended ketamine dose of 0.5 mg/kg will be administered using a transmucosal route of administration wherein the subject will be instructed to place the liquid solution beneath their tongue and hold it in their mouth for 5 minutes. The pharmacy will prepare two 0.5 mg/kg solutions of ketamine in two syringes for each subject based on subject weight. For example, a 70 kg adult subject will receive a 0.35 mL solution of ketamine. The patient will receive a dose every 7 days for two weeks, for a total of two doses.

Drug: Ketamine; Weight-based ketamine dose will be prepared and delivered personally to study physician or study personnel by pharmacy personnel as is done during standard protocol for use of ketamine not part of a clinical study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in depressive symptoms measured by the MADRS.	The Montgomery-Asberg Depression Rating Scale is a ten-item diagnostic questionnaire used by mental health clinicians to measure the severity of depressive episodes in subjects with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. "Reduction of MADRS" = 50% drop in total score as compared to baseline, a score of 0-8 indicating NO depression OR a decrease from a more severe category to a more mild one.	14-day dosing period.
Change in depressive symptoms measured by the MADRS-S.	Montgomery Asberg Depression Rating Scale Self-assessment (MADRS-S). The overall score ranges from 0-54 with a higher scores indicating more depression.	14-day dosing period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Side effects will be evaluated using the PRISE.	Patient-Rated Inventory of Side Effects (PRISE), perceived tolerance per patient report	14-day dosing period.

Collaborators and Investigators

• Sponsor: West Virginia University

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2020
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): November 1, 2022

Study Registration Dates

• First Submitted: May 3, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 6, 2021

Study Record Updates

• Last Update Posted (Actual): April 29, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mood Disorders; Stroke; Depression; Depressive Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Ketamine
• Other Study ID Numbers: 1903509572

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes