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HealthyEarly Phase 1NCT04928703

Effects of Ketamine on ERP/EEG Measures in Healthy Volunteers

A Early Phase 1 study testing Ketamine in people with Healthy, run by ERP Biomarker Qualification Consortium at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 21 to 40 yearsHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Ketamine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
33 participants
Where
1 siteUnited States
Study dates
26 May 2022to 12 Dec 2022
Phase
Early Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 40 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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).
  • A history of additional risk factors for Torsade de Pointes (such as heart failure, hypokalaemia, or family history of Long QT Syndrome).
  • 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.
  • Human immunodeficiency virus (HIV) infection, hepatitis, or other ongoing infectious disease that the investigator considers clinically significant.
  • History of gastrointestinal disease or surgery (except simple appendectomy or hernia repair), which can influence the absorption of the study drug.
  • Evidence of an infection at the time of clinic admission, in the opinion of the investigator.
  • Received an investigational product or device within 30 days (or 5 half-lives, whichever is longer) of dosing.
  • Use of first generation, sedating H1 antihistamines or sedative-hypnotic medications within 1 week prior to dosing.
  • Poor venous access; or have donated or had a significant loss of blood or plasma within 8 weeks of dosing.
  • Known allergy to latex.
  • Prior adverse reaction to ketamine or esketamine.
  • Medical history, conditions, or situations that, in the opinion of the investigator, would preclude safe study participation, or interfere with study procedures/assessments.
  • In addition to these criteria, the investigator may discontinue subjects at any time based on his or her clinical judgment.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Hassman Research Institute

    Marlton, New Jersey, 08053

Other trials in United States

About this study

Official title: A Phase 0, Double-Blind, Randomized, Placebo-Controlled, Crossover Study to Assess Ketamine-induced Changes in ERP Biomarkers in Healthy Volunteers

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.

Read the detailed description

The effects of ketamine and similar compounds on brain function have become of significant interest to pharma companies in the past few years. These effects are often used as a model for the glutamatergic hypofunction hypothesis of schizophrenia and therefore drugs targeting schizophrenia are being trialed to reverse or block the effects of ketamine. Esketamine has been recently approved as a potent treatment for depression so many pharma companies are trying to leverage ketamine-like modulation of the NMDA receptors as novel targets for depression.

This heightened focus on NMDAr modulators has lead industry and academia to advance methods to measure these effects. Many studies have been performed using EEG and ERP techniques to measure the effect on brain function of ketamine administration but no study has been performed, to our knowledge, that has attempted to measure the variability and reproducibility of these effects. Furthermore, there is some evidence from the scientific literature and from unpublished results from industry-sponsored studies that ketamine may have a disordinal effect on various electrophysiologic measures, particularly the amplitude of the mismatch negativity (MMN) from an auditory oddball ERP test.

In this study we will run various EEG/ERP tests on participants during a placebo administration and during two ketamine administrations separated by washout periods. This will allow, for the first time, the evaluation of the test-retest variability of a range ERP/EEG measures under ketamine administration vs placebo. This may also allow us to test the hypothesis that ketamine has a disordinal effect on different subjects and this disordinality can be predicted from a baseline (placebo) measurement.

Conditions
Healthy
Being tested
Ketamine
Keywords
Event-related potential, Electroencephalogram, ERP, EEG, Ketamine, Mismatch Negativity, MMN, N100, P3a, P3b, P300

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04928703
Study groupRoleWhat they receive
Arm 1ExperimentalVisit 2: Placebo - Placebo; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Ketamine
Receives: Drug: Ketamine
Arm 2ExperimentalVisit 2: Placebo - Ketamine; Visit 3: Placebo - Placebo; Visit 4: Placebo - Ketamine
Receives: Drug: Ketamine
Arm 3ExperimentalVisit 2: Placebo - Ketamine; Visit 3: Placebo - Ketamine; Visit 4: Placebo - Placebo
Receives: Drug: Ketamine

What is being measured

The primary outcome is the main question the study is designed to answer.

  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
    2. MMN

    Measured: Pre-intervention/Dosing

Secondary outcomes (22)

  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
    2. N100
    3. P3a
    4. Active, Auditory Oddball ERP
    5. N100
    6. N200
    7. P3b

    Measured: Pre-intervention/Dosing

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

    Latency changes (in milliseconds) for the following parameters from the ERP tests:

    1. Passive, Duration-deviant, Oddball ERP
    2. N100
    3. MMN
    4. P3a
    5. Active, Auditory Oddball ERP
    6. N100
    7. N200
    8. P3b

    Measured: Pre-intervention/Dosing

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

    Change in Task Accuracy as a percentage of correct behavioral responses during the active, auditory oddball ERP test.

    Measured: Pre-intervention/Dosing

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

    Change in Reaction Time for the correct behavioral responses measured in milliseconds during the active, auditory oddball ERP test.

    Measured: Pre-intervention/Dosing

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

    Change in Evoked Power measured in µv2/Hz from the ASSR paradigm.

    Measured: Pre-intervention/Dosing

  6. Ketamine-induced change in Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm.

    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.

    Measured: Pre-intervention/Dosing

  7. Ketamine-induced changes in Absolute Power for Pharmaco-EEG parameters per IPEG guidelines.

    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

    Measured: Pre-intervention/Dosing

  8. Ketamine-induced changes in Relative Power for Pharmaco-EEG parameters per IPEG guidelines.

    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

    Measured: Pre-intervention/Dosing

  9. Ketamine-induced change in the Dominant Frequency for the Alpha frequency band per IPEG guidelines.

    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.

    Measured: Pre-intervention/Dosing

  10. Ketamine-induced changes in Slow Wave Index per IPEG guidelines.

    Slow Wave Index (SWI) will be calculated as Alpha/(Delta+Theta), and will be measured as ratio. Outcome measure will be change in SWI.

    Measured: Pre-intervention/Dosing

  11. Ketamine-induced changes in Theta/Beta ratio per IPEG guidelines.

    Theta/Beta (TBR) will be measured as ratio. Outcome measure will be change in TBR.

    Measured: Pre-intervention/Dosing

  12. Correlations between Ketamine blood concentration and Ketamine-induced changes in Amplitude for parameters from the ERP tests.

    Correlations between ketamine blood concentration and amplitude changes (in microvolts) for the following parameters from the ERP tests:

    1. Passive, Duration-deviant, Oddball ERP
    2. MMN
    3. Passive, Duration-deviant, Oddball ERP
    4. N100
    5. P3a
    6. Active, Auditory Oddball ERP
    7. N100
    8. N200
    9. P3b

    Measured: Pre-intervention/Dosing

  13. Correlations between Ketamine blood concentration and Ketamine-induced changes in Latency for parameters from the ERP tests.

    Correlations between ketamine blood concentration and latency changes (in milliseconds) for the following parameters from the ERP tests:

    1. Passive, Duration-deviant, Oddball ERP
    2. MMN
    3. Passive, Duration-deviant, Oddball ERP
    4. N100
    5. P3a
    6. Active, Auditory Oddball ERP
    7. N100
    8. N200
    9. P3b

    Measured: Pre-intervention/Dosing

  14. Correlation between Ketamine blood concentration and Ketamine-induced change in Task Accuracy from the behavioral response during the active, auditory oddball ERP test.

    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.

    Measured: Pre-intervention/Dosing

  15. Correlation between Ketamine blood concentration and Ketamine-induced change in Reaction Time from the behavioral response during the active, auditory oddball ERP test.

    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.

    Measured: Pre-intervention/Dosing

  16. Correlation between Ketamine blood concentration and Ketamine-induced change in Evoked Power from the auditory steady-state response (ASSR) paradigm.

    Correlation between Ketamine blood concentration and change in Evoked Power measured in µv2/Hz from the ASSR paradigm.

    Measured: Pre-intervention/Dosing

  17. Correlation between Ketamine blood concentration and Ketamine-induced change in Inter-trial coherence (ITC) from the auditory steady-state response (ASSR) paradigm.

    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).

    Measured: Pre-intervention/Dosing

  18. Correlation between Ketamine blood concentration and Ketamine-induced changes in Absolute Power for Pharmaco-EEG parameters.

    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

    Measured: Pre-intervention/Dosing

  19. Correlation between Ketamine blood concentration and Ketamine-induced changes in Relative Power for Pharmaco-EEG parameters.

    Correlation between Ketamine blood concentration and changes in Relative Power for the following Pharmaco-EEG parameters:

    • Delta power
    • Theta power
    • Alpha power
    • Beta power

    Measured: Pre-intervention/Dosing

  20. Correlation between Ketamine blood concentration and Ketamine-induced change in the Dominant Frequency for the Alpha frequency band.

    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.

    Measured: Pre-intervention/Dosing

  21. Correlation between Ketamine blood concentration and Ketamine-induced changes in Slow Wave Index.

    Correlation between Ketamine blood concentration and changes Slow Wave Index (SWI) calculated as Alpha/(Delta+Theta) ratio.

    Measured: Pre-intervention/Dosing

  22. Correlation between Ketamine blood concentration and Ketamine-induced changes in Theta/Beta ratio.

    Correlation between Ketamine blood concentration and changes in Theta/Beta ratio (TBR).

    Measured: Pre-intervention/Dosing

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Jun 2021
  2. Study start26 May 2022
  3. Primary completion12 Dec 2022
  4. Study completion12 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Early Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Model description
Single Dose, Placebo-Controlled, 3-Arm Crossover
Masking
Triple blind
Who is masked
Participant, Investigator, Outcomes assessor
Enrolment
33 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04928703
Sponsor's protocol ID
EBS-B
Status last verified
Feb 2023
First submitted
28 May 2021
Last updated
21 Feb 2023
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Early Phase 1 study testing Ketamine in people with Healthy, run by ERP Biomarker Qualification Consortium at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Ketamine-induced changes in Amplitude for parameters from the ERP tests. (time frame: Pre-intervention/Dosing). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04928703.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.

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