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Trial record 6 of 6 for:    cognision

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

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Ketamine Early Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
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
Official Title: A Phase 0, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to Assess Ketamine-induced Changes in ERP Biomarkers in Healthy Volunteers
Actual Study Start Date : May 26, 2022
Estimated Primary Completion Date : November 30, 2022
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Ketamine

Arm Intervention/treatment
Experimental: Arm 1
Visit 2: Placebo - Placebo; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Ketamine
Drug: Ketamine
Ketamine IV administration

Experimental: Arm 2
Visit 2: Placebo - Ketamine; Visit 3: Placebo - Placebo; Visit 4: Placebo - Ketamine
Drug: Ketamine
Ketamine IV administration

Experimental: Arm 3
Visit 2: Placebo - Ketamine; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Placebo
Drug: Ketamine
Ketamine IV administration




Primary Outcome Measures :
  1. 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



Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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).

  18. 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

  19. 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

  20. 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.

  21. 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.

  22. 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   21 Years to 40 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04928703


Contacts
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Contact: KC Fadem 502 561 9040 ext 7001 kfadem@cognision.com

Locations
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United States, New Jersey
Hassman Research Institute Recruiting
Marlton, New Jersey, United States, 08053
Contact: Jacquelyn Bordelon, BS    856-753-7335 ext 726    jbordelon@hritrials.com   
Contact: Jessica Ortega, BS    856-361-5438    jortega@hritrials.com   
Principal Investigator: Elan Cohen, PhD         
Sponsors and Collaborators
ERP Biomarker Qualification Consortium
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
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Principal Investigator: Marco Cecchi, PhD The ERP Biomarker Qualification Consortium
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Responsible Party: ERP Biomarker Qualification Consortium
ClinicalTrials.gov Identifier: NCT04928703    
Other Study ID Numbers: EBS-B
First Posted: June 16, 2021    Key Record Dates
Last Update Posted: June 6, 2022
Last Verified: June 2022

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by ERP Biomarker Qualification Consortium:
Event-related potential
Electroencephalogram
ERP
EEG
Ketamine
Mismatch Negativity
MMN
N100
P3a
P3b
P300
Additional relevant MeSH terms:
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Ketamine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action