An EEG Study of Intravenous Ketamine for Major Depression Disorder

An Open Label Study of Electroencephalographic Responses Pre, During and Post, a Low Dose, Weekly Intravenous Ketamine Infusion for 4 Weeks, in a Study Population With Major Depression Disorder

There are many common pharmacological treatments for major depression disorder (MDD), however the efficacy of these drugs often fails in severe cases. Intravenous (IV) administered ketamine may offer the potential for remission of the symptoms in patients with MDD; however it has not yet been approved by FDA for this purpose. This study will make use of an electroencephalography (EEG) machine to measure the brain's activity and response while the IV ketamine is being delivered. The objective of this study is to characterize the change in EEG response of patients with MDD, during and 4 weeks after a course of IV ketamine infusions.

Study Overview

• Status: Not yet recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Ketamine Hydrochloride

Detailed Description

This study will enroll 35 patients with major depressive disorder. Candidates for participation in the study will typically be either referred to the clinic through their healthcare provider or will have sought out participation on their own accord based on advertising. Subjects will be screened for eligibility and suitable patients will be invited to attend a screening visit in the clinic and complete informed consent.

Upon determining eligibility, subjects will have their first treatment session booked within 42 days of screening (Baseline, visit 0). Three subsequent weekly (±3 days) ketamine therapy treatment sessions will occur on days 7, 14 and 21, for a total of four ketamine infusions over four weeks. All patients will return for a follow-up visit at 4-weeks post final treatment visit, day 49.

• Study Type: Interventional
• Enrollment (Anticipated): 35
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jeffrey D Kamlet, MD; Phone Number: 305 604 9595; Email: jeffrey@tristarwell.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Individuals between 18 and 70 years of age, inclusive
2. Adult patients with a documented primary Axis I clinical diagnosis meeting criteria from the DSM-V for a major depressive disorder
3. Score of <15 on the DES
4. Moderate to severe symptoms objectively documented using MADRS total score of ≥ 20
5. Ability to maintain scheduled appointments for screenings, 4 treatment visits and follow-up EEG visit.
6. History of major depressive disorder.
7. Females of child-bearing potential who are sexually active must agree to use two forms of contraception. A pregnancy test will be performed before the first treatment.
8. Must have stable residence address, internet and mobile phone.
9. Must speak fluent English.

Exclusion Criteria:

1. Known allergy to ketamine or any other drug used in the study.
2. Use of ketamine in a therapeutic model within the preceding 12 months of the study.
3. Current or any history of schizoaffective disorder(s).
4. Score of ≥ 15 on DES
5. History of illicit active substance abuse or dependence including ketamine as determined on by the SCID-5-CT and/or drug urine screening during study visits.
6. Pregnancy, breastfeeding or desire to become pregnant during the course of the study.
7. Serious, unstable illnesses including, but not limited to; hepatic, gastro-intestinal, respiratory, cardiovascular (including ischemic heart disease and coronary heart disease). History of ischemic stroke, atrial fibrillation, severe endocrinological, neurological, immunological or hematological disease.
8. Any history of cerebral vascular events including stroke, bleeding into the brain and subdural hematomas.
9. Any implantable metallic device(s) or implant(s) above the level of shoulders.
10. Any non-removable metallic piercings.
11. Patients with cochlear implants and non-removable hearing aids.
12. Current use of: Dilantin, Depakote, Phenobarbital, Gabapentin, Pregabalin and Benzodiazepines. Certain candidates with long use of Benzodiazepines may qualify at PI's discretion.
13. Severe labile hypertension.
14. Significant uncontrolled hypertension (i.e., SBP > 150 mmHG, DBP > 100 mmHG)
15. Uncontrolled diabetes mellitus.
16. Patients on renal dialysis.
17. Inability to achieve consistent IV access.

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; 50-60 minutes intravenous infusion of 60mg ketamine	Drug: Ketamine Hydrochloride; Patients with a diagnosis of Major Depressive Disorder (MDD) will be enrolled to receive four 50-60 minute infusions of 60mg ketamine hydrochloride; Other Names: NDC 67457-108-00

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterizing the changes in EEG reading frequencies from pre- IV ketamine infusion treatment (baseline).	Alpha, Beta, Delta, Theta and Gamma frequencies will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	30-minute pre-treatment baseline and throughout infusion (approximately 50-60 minutes)
Characterizing the changes in EEG reading waveforms from pre- IV ketamine infusion treatment (baseline).	Alpha, Beta, Delta, Theta and Gamma waveforms will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	30-minute pre-treatment baseline and throughout infusion (approximately 50-60 minutes)
Characterizing the changes in EEG reading amplitudes from pre- IV ketamine infusion treatment (baseline).	Alpha, Beta, Delta, Theta and Gamma amplitude will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	30-minute pre-treatment baseline and throughout infusion (approximately 50-60 minutes)
Characterizing the changes in EEG reading patterns from pre- IV ketamine infusion treatment (baseline).	Alpha, Beta, Delta, Theta and Gamma reading patterns will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	30-minute pre-treatment baseline and throughout infusion (approximately 50-60 minutes)
Characterizing the changes in EEG reading frequencies from pre- IV ketamine infusion treatment (baseline) and 4 weeks post-treatment course	Alpha, Beta, Delta, Theta and Gamma frequencies will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	Pre-treatment baseline, 4 weeks post-treatment course
Characterizing the changes in EEG reading waveforms from pre- IV ketamine infusion treatment (baseline) and 4 weeks post-treatment course	Alpha, Beta, Delta, Theta and Gamma waveforms will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	Pre-treatment baseline, 4 weeks post-treatment course
Characterizing the changes in EEG reading amplitudes from pre- IV ketamine infusion treatment (baseline) and 4 weeks post-treatment course	Alpha, Beta, Delta, Theta and Gamma amplitude will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	Pre-treatment baseline, 4 weeks post-treatment course
Characterizing the changes in EEG reading patterns from pre- IV ketamine infusion treatment (baseline) and 4 weeks post-treatment course	Alpha, Beta, Delta, Theta and Gamma amplitude will be examined with portable NeuroEEG™, a 19 channels and 22 electrodes cap based on 10-20 distribution	Pre-treatment baseline, 4 weeks post-treatment course

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of medically significant changes in blood pressure during ketamine infusion		Pre-treatment baseline; treatment initiation, 0 minutes; 20 minutes, 40 minutes; 60 minutes post-infusion
Incidence of medically significant changes in Oxygen Saturation (SpO2) during ketamine infusion		Pre-treatment baseline; treatment initiation, 0 minutes; 20 minutes, 40 minutes; 60 minutes post-infusion
Incidence of medically significant changes in heart rate during ketamine infusion		Pre-treatment baseline; treatment initiation, 0 minutes; 20 minutes, 40 minutes; 60 minutes post-infusion
Incidence of medically significant changes in respiratory rate during ketamine infusion		Pre-treatment baseline; treatment initiation, 0 minutes; 20 minutes, 40 minutes; 60 minutes post-infusion
Changes from baseline in the Dissociative Experiences Scale (DES) Total Score	The Dissociative Experiences Scale (DES) is a 28-item scale assessing the subject's experiences in his/her daily life. The subject determines to what degree he/she has been facing the situation by selecting a percentage from 0% (never) to 100% (always), with 10% increments in between. Higher scores mean higher severity	Baseline (Day 0), follow-up visit (Day 42)

Collaborators and Investigators

• Sponsor: Ehave Inc.
• Collaborators: Tristar Wellness
• Investigators: Principal Investigator: Jeffrey D Kamlet, MD, Tristar Wellness

Study record dates

Study Major Dates

• Study Start (Anticipated): January 1, 2023
• Primary Completion (Anticipated): January 1, 2024
• Study Completion (Anticipated): February 1, 2024

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: August 16, 2022
• First Posted (Actual): August 18, 2022

Study Record Updates

• Last Update Posted (Actual): August 22, 2022
• Last Update Submitted That Met QC Criteria: August 18, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Major depressive disorder; Intravenous ketamine; Electroencephalogram (EEG) monitoring
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; 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: 21EERPZ01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No