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Effects of Ketamine on ERP/EEG Measures in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT04928703
Recruitment Status : Recruiting
First Posted : June 16, 2021
Last Update Posted : June 6, 2022
Sponsor:
Collaborators:
Alkermes, Inc.
Anavex Life Sciences Corp.
Astellas Pharma Inc
H. Lundbeck A/S
Merck Sharp & Dohme LLC
Novartis
Sage Therapeutics
Takeda
Apex Innovative Sciences
COGNISION
Information provided by (Responsible Party):
ERP Biomarker Qualification Consortium

Tracking Information
First Submitted Date  ICMJE May 28, 2021
First Posted Date  ICMJE June 16, 2021
Last Update Posted Date June 6, 2022
Actual Study Start Date  ICMJE May 26, 2022
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
Ketamine-induced changes in Amplitude for parameters from the ERP tests. [ Time Frame: Pre-intervention/Dosing ]
Amplitude changes (in microvolts) for the following parameters from the ERP tests: 1. Passive, Duration-deviant, Oddball ERP a. MMN
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 15, 2021)
  • Ketamine-induced changes in Amplitude for parameters from the ERP tests. [ Time Frame: Pre-intervention/Dosing ]
    Amplitude changes (in microvolts) for the following parameters from the ERP tests:
    1. Passive, Duration-deviant, Oddball ERP
      1. N100
      2. P3a
    2. Active, Auditory Oddball ERP
      1. N100
      2. N200
      3. P3b
  • Ketamine-induced changes in Latency for parameters from the ERP tests. [ Time Frame: Pre-intervention/Dosing ]
    Latency changes (in milliseconds) for the following parameters from the ERP tests:
    1. Passive, Duration-deviant, Oddball ERP
      1. N100
      2. MMN
      3. P3a
    2. Active, Auditory Oddball ERP
      1. N100
      2. N200
      3. P3b
  • Ketamine-induced change in Task Accuracy from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: Pre-intervention/Dosing ]
    Change in Task Accuracy as a percentage of correct behavioral responses during the active, auditory oddball ERP test.
  • Ketamine-induced change in Reaction Time from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: Pre-intervention/Dosing ]
    Change in Reaction Time for the correct behavioral responses measured in milliseconds during the active, auditory oddball ERP test.
  • Ketamine-induced change in Evoked Power from the auditory steady-state response (ASSR) paradigm. [ Time Frame: Pre-intervention/Dosing ]
    Change in Evoked Power measured in µv2/Hz from the ASSR paradigm.
  • Ketamine-induced change in Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm. [ Time Frame: Pre-intervention/Dosing ]
    Inter-trial coherence (ITC) from the ASSR paradigm will be measured on a scale between 0 (no coherence) and 1 (maximum coherence). Outcome measure will be change in ITC.
  • Ketamine-induced changes in Absolute Power for Pharmaco-EEG parameters per IPEG guidelines. [ Time Frame: Pre-intervention/Dosing ]
    Changes in Absolute Power (measured in µv2/Hz) for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
    • Gamma power
    • Total power
  • Ketamine-induced changes in Relative Power for Pharmaco-EEG parameters per IPEG guidelines. [ Time Frame: Pre-intervention/Dosing ]
    Relative Power for Pharmaco-EEG parameters will be measured on a scale from 0 (no power in frequency band) to 1 (all EEG power in that frequency band). Outcome measures will be changes in Relative Power for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
  • Ketamine-induced change in the Dominant Frequency for the Alpha frequency band per IPEG guidelines. [ Time Frame: Pre-intervention/Dosing ]
    Dominant frequency will be measured in Hz in the frequency interval between 6.0 and < 12.5 Hz. Outcome measure will be change in the Dominant Frequency for the Alpha frequency band.
  • Ketamine-induced changes in Slow Wave Index per IPEG guidelines. [ Time Frame: Pre-intervention/Dosing ]
    Slow Wave Index (SWI) will be calculated as Alpha/(Delta+Theta), and will be measured as ratio. Outcome measure will be change in SWI.
  • Ketamine-induced changes in Theta/Beta ratio per IPEG guidelines. [ Time Frame: Pre-intervention/Dosing ]
    Theta/Beta (TBR) will be measured as ratio. Outcome measure will be change in TBR.
  • Correlations between Ketamine blood concentration and Ketamine-induced changes in Amplitude for parameters from the ERP tests. [ Time Frame: Pre-intervention/Dosing ]
    Correlations between ketamine blood concentration and amplitude changes (in microvolts) for the following parameters from the ERP tests:
    1. Passive, Duration-deviant, Oddball ERP a. MMN
    2. Passive, Duration-deviant, Oddball ERP
      1. N100
      2. P3a
    3. Active, Auditory Oddball ERP
      1. N100
      2. N200
      3. P3b
  • Correlations between Ketamine blood concentration and Ketamine-induced changes in Latency for parameters from the ERP tests. [ Time Frame: Pre-intervention/Dosing ]
    Correlations between ketamine blood concentration and latency changes (in milliseconds) for the following parameters from the ERP tests:
    1. Passive, Duration-deviant, Oddball ERP a. MMN
    2. Passive, Duration-deviant, Oddball ERP
      1. N100
      2. P3a
    3. Active, Auditory Oddball ERP
      1. N100
      2. N200
      3. P3b
  • Correlation between Ketamine blood concentration and Ketamine-induced change in Task Accuracy from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and change in Task Accuracy measured as a percentage of correct behavioral responses during the active, auditory oddball ERP test.
  • Correlation between Ketamine blood concentration and Ketamine-induced change in Reaction Time from the behavioral response during the active, auditory oddball ERP test. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and change in Reaction Time for the correct behavioral responses measured in milliseconds during the active, auditory oddball ERP test.
  • Correlation between Ketamine blood concentration and Ketamine-induced change in Evoked Power from the auditory steady-state response (ASSR) paradigm. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and change in Evoked Power measured in µv2/Hz from the ASSR paradigm.
  • Correlation between Ketamine blood concentration and Ketamine-induced change in Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and change in Inter-trial coherence (ITC) from the ASSR paradigm. Change in ITC will be measured on a scale between 0 (no coherence) and 1 (maximum coherence).
  • Correlation between Ketamine blood concentration and Ketamine-induced changes in Absolute Power for Pharmaco-EEG parameters. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and changes in Absolute Power (measured in µv2/Hz) for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
    • Gamma power
    • Total power
  • Correlation between Ketamine blood concentration and Ketamine-induced changes in Relative Power for Pharmaco-EEG parameters. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and changes in Relative Power for the following Pharmaco-EEG parameters:
    • Delta power
    • Theta power
    • Alpha power
    • Beta power
  • Correlation between Ketamine blood concentration and Ketamine-induced change in the Dominant Frequency for the Alpha frequency band. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and Dominant frequency for the Alpha frequency band measured in Hz in the frequency interval between 6.0 and < 12.5 Hz.
  • Correlation between Ketamine blood concentration and Ketamine-induced changes in Slow Wave Index. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and changes Slow Wave Index (SWI) calculated as Alpha/(Delta+Theta) ratio.
  • Correlation between Ketamine blood concentration and Ketamine-induced changes in Theta/Beta ratio. [ Time Frame: Pre-intervention/Dosing ]
    Correlation between Ketamine blood concentration and changes in Theta/Beta ratio (TBR).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effects of Ketamine on ERP/EEG Measures in Healthy Volunteers
Official Title  ICMJE A Phase 0, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to Assess Ketamine-induced Changes in ERP Biomarkers in Healthy Volunteers
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Early Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Single Dose, Placebo-Controlled, 3-Arm Crossover
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Other
Condition  ICMJE Healthy
Intervention  ICMJE Drug: Ketamine
Ketamine IV administration
Study Arms  ICMJE
  • Experimental: Arm 1
    Visit 2: Placebo - Placebo; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Ketamine
    Intervention: Drug: Ketamine
  • Experimental: Arm 2
    Visit 2: Placebo - Ketamine; Visit 3: Placebo - Placebo; Visit 4: Placebo - Ketamine
    Intervention: Drug: Ketamine
  • Experimental: Arm 3
    Visit 2: Placebo - Ketamine; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Placebo
    Intervention: Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 15, 2021)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2022
Estimated Primary Completion Date November 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy male and female subjects 21-40 years of age, inclusive at Visit 1 (Screening).
  2. 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.
  3. 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.
  4. Subject is judged to be in good health as determined by the investigator.
  5. Body mass index (BMI ) between 18.5 and 30.0 (inclusive) at Visit 1 (Screening).
  6. Ability to detect a 1000 and 2000 Hz tone at 40 dB in both ears, at Visit 1 (Screening).
  7. Ability to tolerate the electrode cap for the duration of the testing session.

Exclusion Criteria:

  1. 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.
  2. 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.
  3. 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.
  4. Use of products containing nicotine (tobacco or vaping products) 60 minutes prior to dosing on Visits 2-4.
  5. 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.
  6. History of allergy, sensitivity, or intolerance to NMDAR ligands including ketamine, amantadine, dextromethorphan, memantine, methadone, dextropropoxyphene, or ketobemidone.
  7. Any impairment, activity, or situation that in the judgment of the investigator would prevent satisfactory completion of the study protocol.
  8. 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).
  9. 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.
  10. History of severe renal or hepatic impairment, in the opinion of the investigator or the sponsor medical monitor.
  11. Known history of significant cardiovascular condition such as myocardial infarction, congestive heart failure, clinically significant arrhythmias, current uncontrolled cardiac arrhythmias, angina, acute ischemia.
  12. 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.
  13. Hypotension with an abnormal supine blood pressure defined as SBP < 90 mmHg or DBP <60 mmHg at any Visit.
  14. 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.
  15. Resting heart rate < 45 or > 95 beats per minute.
  16. A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are repeatedly greater than 450 ms) or any other relevant ECG finding at Visit 1 (Screening).
  17. A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome).
  18. Current evidence of dysplasia or history of malignancy (including lymphoma and leukemia) in the last 5 years, with the exception of successfully treated non-metastatic basal cell or squamous cell carcinoma of the skin or localized carcinoma in situ of the cervix.
  19. Human immunodeficiency virus (HIV) infection, hepatitis, or other ongoing infectious disease that the investigator considers clinically significant.
  20. History of gastrointestinal disease or surgery (except simple appendectomy or hernia repair), which can influence the absorption of the study drug.
  21. Evidence of an infection at the time of clinic admission, in the opinion of the investigator.
  22. Received an investigational product or device within 30 days (or 5 half-lives, whichever is longer) of dosing.
  23. Use of first generation, sedating H1 antihistamines or sedative-hypnotic medications within 1 week prior to dosing.
  24. Poor venous access; or have donated or had a significant loss of blood or plasma within 8 weeks of dosing.
  25. Known allergy to latex.
  26. Prior adverse reaction to ketamine or esketamine.
  27. Medical history, conditions, or situations that, in the opinion of the investigator, would preclude safe study participation, or interfere with study procedures/assessments.
  28. In addition to these criteria, the investigator may discontinue subjects at any time based on his or her clinical judgment.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 40 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: KC Fadem 502 561 9040 ext 7001 kfadem@cognision.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04928703
Other Study ID Numbers  ICMJE EBS-B
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party ERP Biomarker Qualification Consortium
Original Responsible Party Same as current
Current Study Sponsor  ICMJE ERP Biomarker Qualification Consortium
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE
  • Alkermes, Inc.
  • Anavex Life Sciences Corp.
  • Astellas Pharma Inc
  • H. Lundbeck A/S
  • Merck Sharp & Dohme LLC
  • Novartis
  • Sage Therapeutics
  • Takeda
  • Apex Innovative Sciences
  • COGNISION
Investigators  ICMJE
Principal Investigator: Marco Cecchi, PhD The ERP Biomarker Qualification Consortium
PRS Account ERP Biomarker Qualification Consortium
Verification Date June 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP