Effects of Ketamine on ERP/EEG Measures in Healthy Volunteers

NCT04928703 | Completed Early Phase 1

• 1 other identifier: EBS-B
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 0, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to assess the changes in ERP Biomarkers in Healthy Volunteers before and after administration of a sub-anesthetic dose of ketamine. Primary objectives are to quantify the effect size of ketamine-induced changes on MMN from a duration-deviant auditory oddball ERP test and to quantify the variability of ketamine-induced changes on MMN from a duration-deviant auditory oddball ERP test.

Conditions

Healthy

Keywords

Event-related potential; Electroencephalogram; ERP; EEG; Ketamine; Mismatch Negativity; MMN; N100; P3a; P3b; P300

Outcome Measures

Primary Outcomes (1)

• Ketamine-induced changes in Amplitude for parameters from the ERP tests.

  Amplitude changes (in microvolts) for the following parameters from the ERP tests: 1\. Passive, Duration-deviant, Oddball ERP a. MMN

  Pre-intervention/Dosing

Secondary Outcomes (22)

• Ketamine-induced changes in Amplitude for parameters from the ERP tests.

  Pre-intervention/Dosing

• Ketamine-induced changes in Latency for parameters from the ERP tests.

  Pre-intervention/Dosing

• Ketamine-induced change in Task Accuracy from the behavioral response during the active, auditory oddball ERP test.

  Pre-intervention/Dosing

• Ketamine-induced change in Reaction Time from the behavioral response during the active, auditory oddball ERP test.

  Pre-intervention/Dosing

• Ketamine-induced change in Evoked Power from the auditory steady-state response (ASSR) paradigm.

  Pre-intervention/Dosing

Study Arms (3)

Arm 1

EXPERIMENTAL

Visit 2: Placebo - Placebo; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Ketamine

Drug: Ketamine

Arm 2

EXPERIMENTAL

Visit 2: Placebo - Ketamine; Visit 3: Placebo - Placebo; Visit 4: Placebo - Ketamine

Drug: Ketamine

Arm 3

EXPERIMENTAL

Visit 2: Placebo - Ketamine; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Placebo

Drug: Ketamine

Interventions

Ketamine DRUG

Ketamine IV administration

Arm 1; Arm 2; Arm 3

Eligibility Criteria

• Age: 21 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male and female subjects 21-40 years of age, inclusive at Visit 1 (Screening).
• Female subjects with a negative serum pregnancy test prior to entry into the study and who are practicing an adequate method of birth control (e.g., oral or parenteral contraceptives, intrauterine device, barrier, abstinence) and who do not plan to become pregnant during the study and for 30 days after the last dose of ketamine.
• Ability to understand the requirements of the study, provide written informed consent, abide by the study restrictions, and agree to return for the required assessments.
• Subject is judged to be in good health as determined by the investigator.
• Body mass index (BMI ) between 18.5 and 30.0 (inclusive) at Visit 1 (Screening).
• Ability to detect a 1000 and 2000 Hz tone at 40 dB in both ears, at Visit 1 (Screening).
• Ability to tolerate the electrode cap for the duration of the testing session.

You may not qualify if:

• Clinically significant alcohol or other substance abuse within the last 1 year, in the opinion of the investigator; or unable to abstain from alcoholic beverages during the course of the study.
• Positive alcohol/drug screen for drugs of abuse (with the exception of a positive result considered by the investigator to be directly attributable to prescription medication approved for subject use) such as phencyclidine, benzodiazepines, opiates, cocaine, cannabinoids, amphetamines, and cotinine at any Visit.
• Excessive caffeine use (defined as habitual consumption of \> 400 mg caffeine per day \[\~ four 8 oz. cups brewed caffeinated coffee or tea, \~ ten 12 oz. cans caffeinated soda or \~ two "energy shot" drinks\]), or unable to abstain from caffeine on Visits 2-4.
• Use of products containing nicotine (tobacco or vaping products) 60 minutes prior to dosing on Visits 2-4.
• Current or prior history (defined as in the past 6 months) of treatment with N-methyl-D-aspartate receptor (NMDAR) ligands including ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
• History of allergy, sensitivity, or intolerance to NMDAR ligands including ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
• Any impairment, activity, or situation that in the judgment of the investigator would prevent satisfactory completion of the study protocol.
• History of significant psychiatric, neurologic (e.g. Huntington's, Parkinson's, Alzheimer's, Multiple Sclerosis, Type I or Type II diabetes mellitus, or a history of seizures, epilepsy, or strokes), or cognitive disorders (e.g. bipolar, schizophrenia, psychosis), or current (within 12 months prior to screening) psychiatric or cognitive disorders such as major depression, suicidal ideation, dementia, or anxiety disorders).
• Abnormal medical history, or concurrent conditions that, in the opinion of the investigator or sponsor designated medical monitor, would preclude safe study participation, or interfere with study procedures/assessments.
• History of severe renal or hepatic impairment, in the opinion of the investigator or the sponsor medical monitor.
• Known history of significant cardiovascular condition such as myocardial infarction, congestive heart failure, clinically significant arrhythmias, current uncontrolled cardiac arrhythmias, angina, acute ischemia.
• Hypertension characterized by resting systolic blood pressure \> 140 mmHg or resting diastolic \> 90 mmHg or tachycardia defined as a resting HR ≥ 120 bpm or bradycardia defined as a resting HR of ≤ 50 bpm, at any Visit.
• Hypotension with an abnormal supine blood pressure defined as SBP \< 90 mmHg or DBP \<60 mmHg at any Visit.
• Orthostatic hypotension consisting of a SBP change of ≥ 30 mmHg or a DBP change of ≥ 20 mmHg at 3 minutes after standing from a supine position at any Visit.
• Resting heart rate \< 45 or \> 95 beats per minute.

Sponsors & Collaborators

• ERP Biomarker Qualification Consortium: lead
• Alkermes, Inc.: collaborator
• Anavex Life Sciences Corp.: collaborator
• Astellas Pharma Inc: collaborator
• H. Lundbeck A/S: collaborator
• Merck Sharp & Dohme LLC: collaborator
• Novartis: collaborator
• Sage Therapeutics: collaborator
• Takeda: collaborator
• Apex Innovative Sciences: collaborator
• COGNISION: collaborator

Study Sites (1)

Hassman Research Institute

Marlton, New Jersey, 08053, United States

Location

MeSH Terms

Interventions

Ketamine

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Marco Cecchi, PhD

  The ERP Biomarker Qualification Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single Dose, Placebo-Controlled, 3-Arm Crossover

Study Record Dates

• First Submitted: May 28, 2021
• First Posted: June 16, 2021
• Study Start: May 26, 2022
• Primary Completion: December 12, 2022
• Study Completion: December 12, 2022
• Last Updated: February 21, 2023

Record last verified: 2023-02

Locations

US (1)