Trial Outcomes & Findings for Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus (NCT NCT03336398)
NCT ID: NCT03336398
Last Updated: 2026-03-25
Results Overview
The GABA and Glutamate/Glutamine (Glx) peaks will be quantified as ratios (relative to water) and are obtained from the auditory cortex using 3T Magnetic Resonance Spectroscopy (MRS). Brain spectra containing GABA and Glutamate/Glutamine (Glx) resonances will be acquired of the auditory cortex using the volume-selective PRESS J-editing difference method. Data will be acquired from a voxel centered on Heschl's sulcus. The GABA and Glx peak areas will be quantified as ratios relative to the area of the unsuppressed voxel tissue water. The primary outcomes are GABA and GLX levels (relative to water) as they are obtained over time in frames reported as least squares mean with standard error. The first two frames serve as baseline measures, while frames 3 through 8 occur after the infusion over 40 minutes. This will be reported for saline and ketamine scans. An increase in GABA/water may correlate with tinnitus improvement, based on previous MRS studies showing low GABA/water in tinnitus.
COMPLETED
PHASE2
42 participants
GABA and GLX are binned into frames before and after the infusion. The pre-infusion frames (1 and 2) include about 12 minutes of data. The post-infusion frames occur over 40 minutes following the delivery of ketamine/saline (frames 3 through 8).
2026-03-25
Participant Flow
Participants recruited by advertisements and word of mouth.
All participants received saline and ketamine on separate days (the saline scan occurred first for all participants. The saline scan day provided a test-retest measure of GABA/Glx. On ketamine scan days, the MRS measures of GABA/Glx were obtained before and after the ketamine infusion. The subjective outcomes were obtained before are after each scan.
Participant milestones
| Measure |
Participants With Tinnitus
Participants who experience tinnitus will receive both 0.5 mg/kg ketamine hydrochloride in saline and placebo, saline, with Magnetic Resonance Spectroscopy scans and audiometry testing and scales.
Ketamine Hydrochloride in saline: 0.5 mg/kg IV of ketamine hydrochloride in saline will be administered with one of the MRS Scan
Saline: Saline will be administered with the other MRS scan
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Overall Study
STARTED
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42
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Overall Study
Participants Receiving Ketamine
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39
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Overall Study
Participants Receiving Saline
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41
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Overall Study
COMPLETED
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39
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Overall Study
NOT COMPLETED
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3
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus
Baseline characteristics by cohort
| Measure |
Participants With Tinnitus
n=42 Participants
Participants who experience tinnitus. This group will receive both 0.5 mg/kg ketamine hydrochloride in saline and placebo, saline, with Magnetic Resonance Spectroscopy scans and audiometry testing and scales.
Ketamine Hydrochloride in saline: 0.5 mg/kg IV of ketamine hydrochloride in saline will be administered with one of the MRS Scan
Saline: Saline will be administered with the other MRS scan
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Age, Continuous
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43 years
STANDARD_DEVIATION 12 • n=138 Participants
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Sex: Female, Male
Female
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18 Participants
n=138 Participants
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Sex: Female, Male
Male
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24 Participants
n=138 Participants
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Race (NIH/OMB)
American Indian or Alaska Native
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1 Participants
n=138 Participants
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Race (NIH/OMB)
Asian
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4 Participants
n=138 Participants
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Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
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0 Participants
n=138 Participants
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Race (NIH/OMB)
Black or African American
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4 Participants
n=138 Participants
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Race (NIH/OMB)
White
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30 Participants
n=138 Participants
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Race (NIH/OMB)
More than one race
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2 Participants
n=138 Participants
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Race (NIH/OMB)
Unknown or Not Reported
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1 Participants
n=138 Participants
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PRIMARY outcome
Timeframe: GABA and GLX are binned into frames before and after the infusion. The pre-infusion frames (1 and 2) include about 12 minutes of data. The post-infusion frames occur over 40 minutes following the delivery of ketamine/saline (frames 3 through 8).Population: participants who completed the MRS scans with ketamine
The GABA and Glutamate/Glutamine (Glx) peaks will be quantified as ratios (relative to water) and are obtained from the auditory cortex using 3T Magnetic Resonance Spectroscopy (MRS). Brain spectra containing GABA and Glutamate/Glutamine (Glx) resonances will be acquired of the auditory cortex using the volume-selective PRESS J-editing difference method. Data will be acquired from a voxel centered on Heschl's sulcus. The GABA and Glx peak areas will be quantified as ratios relative to the area of the unsuppressed voxel tissue water. The primary outcomes are GABA and GLX levels (relative to water) as they are obtained over time in frames reported as least squares mean with standard error. The first two frames serve as baseline measures, while frames 3 through 8 occur after the infusion over 40 minutes. This will be reported for saline and ketamine scans. An increase in GABA/water may correlate with tinnitus improvement, based on previous MRS studies showing low GABA/water in tinnitus.
Outcome measures
| Measure |
Tinnitus Patients
n=39 Participants
Tinnitus patients with symptoms over 6 months duration. Data will be obtained before and after 0.5 mg/kg ketamine hydrochloride in saline with Magnetic Resonance Spectroscopy scans and audiometry testing and scales.
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 7
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2.10 Ratio
Standard Deviation 0.23
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 1
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2.14 Ratio
Standard Deviation 0.21
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 7
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2.13 Ratio
Standard Deviation 0.19
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 5
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11.83 Ratio
Standard Deviation 1.28
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 5
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2.05 Ratio
Standard Deviation 0.19
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 6
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2.07 Ratio
Standard Deviation 0.26
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 8
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2.05 Ratio
Standard Deviation 0.2
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 2
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2.11 Ratio
Standard Deviation 0.21
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 3
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2.07 Ratio
Standard Deviation 0.19
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 4
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2.05 Ratio
Standard Deviation 0.19
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 5
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2.12 Ratio
Standard Deviation 0.25
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 6
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2.15 Ratio
Standard Deviation 0.24
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GABA frame 8
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2.11 Ratio
Standard Deviation 0.22
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 1
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11.92 Ratio
Standard Deviation 1.01
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 2
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11.84 Ratio
Standard Deviation 1.09
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 3
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11.83 Ratio
Standard Deviation 1.38
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 4
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11.84 Ratio
Standard Deviation 1.34
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 5
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11.84 Ratio
Standard Deviation 1.34
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 6
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11.91 Ratio
Standard Deviation 1.28
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 7
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11.80 Ratio
Standard Deviation 1.38
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GLX frame 8
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11.77 Ratio
Standard Deviation 1.55
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 1
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11.90 Ratio
Standard Deviation 0.79
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 2
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11.78 Ratio
Standard Deviation 0.87
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 3
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11.72 Ratio
Standard Deviation 0.84
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 4
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11.83 Ratio
Standard Deviation 1.09
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 6
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11.58 Ratio
Standard Deviation 1.40
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 7
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11.56 Ratio
Standard Deviation 1.47
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
ketamine scan GLX frame 8
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11.53 Ratio
Standard Deviation 1.35
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 1
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2.11 Ratio
Standard Deviation 0.19
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 2
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2.12 Ratio
Standard Deviation 0.22
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 3
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2.09 Ratio
Standard Deviation 0.21
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GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy
Saline scan GABA frame 4
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2.03 Ratio
Standard Deviation 0.16
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Adverse Events
Tinnitus Patients Ketamine Scan Day
Tinnitus Patients Saline Scan Day
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Tinnitus Patients Ketamine Scan Day
n=42 participants at risk
This group will receive both 0.5 mg/kg ketamine hydrochloride in saline and placebo, saline, with Magnetic Resonance Spectroscopy scans and audiometry testing and scales.
Ketamine Hydrochloride in saline: 0.5 mg/kg IV of ketamine hydrochloride in saline will be administered with one of the MRS Scan
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Tinnitus Patients Saline Scan Day
n=42 participants at risk
This group will receive both 0.5 mg/kg ketamine hydrochloride in saline and placebo, saline, with Magnetic Resonance Spectroscopy scans and audiometry testing and scales.
Saline will be administered with one of the MRS Scan
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Nervous system disorders
dizziness
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7.1%
3/42 • Number of events 3 • Duration of study (2-4 weeks)
Participants were asked about adverse events.
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2.4%
1/42 • Number of events 1 • Duration of study (2-4 weeks)
Participants were asked about adverse events.
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place