CompletedPhase 2

Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus

United States42 participantsStarted 2019-09-01

Plain-language summary

Tinnitus, or ringing in the ears, is a very common problem that often accompanies hearing loss. It affects up to 1 in 10 adults, and about 30% of people who experience chronic tinnitus find it very distressing. In these patients, symptoms of depression and anxiety often accompany tinnitus and there are no approved treatments. Clinical trials are ongoing to test a glutamate NMDA receptor antagonist (called esketamine), which is injected into the inner ear. However, the preliminary results with this medication show that it only works for tinnitus that results from acute injury. It does not treat tinnitus resulting from progressive hearing loss. Research in humans and animals suggest that the neurotransmitters glutamate and GABA are important in the development and maintenance of tinnitus. This data shows that over-activation of the NMDA receptor and a decrease in GABA signaling in the brain play a crucial role. Previous studies show that ketamine, which an antagonist at the NMDA receptor, increases GABA levels in the brain in participants with depression. Thus, in this experiment, this study will test the effect of ketamine on tinnitus, since it blocks the NMDA glutamate receptor and increase GABA levels. Two groups of participants will be included in this study: those who experience distress (symptoms of anxiety or depression) with tinnitus and those who have tinnitus but do not experience distress. Each participant will receive both ketamine and placebo on different days. Magnetic Resonance Spectroscopy (MRS) scans will be

Who can participate

Age range21 Years – 60 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: * Participant aged 21-60 * Tinnitus associated with at least mild sensori-neural hearing loss of at least 6 months duration * Score at least 32 on the Tinnitus Handicap Inventory and a score of 5dB or greater on the minimum masking level * Tinnitus not due to medical disease (other than sensorineural hearing loss) * Score of at least 14 on the Hamilton Depression Rating Scales with a score of at least 2 on the Hamilton Anxiety Rating Scale (in the distressed group). Exclusion Criteria: * DSM-V psychiatric disorders other than mild-moderate depression and anxiety, including substance use disorder. * History of recreational ketamine use, recreational PCP use,exposure to ketamine as an anesthetic, or an adverse reaction to ketamine * Currently taking psychotropic medication (e.g.antipsychotics, antidepressants, benzodiazepines) * Presence or positive history of significant medical or neurological illness, including high blood pressure (SBP \>140, DBP \> 90), cardiac illness, abnormality on EKG, head injury. * Pregnancy, abortion, or lack of effective birth control during 15 days before the scan * Metal implants, pacemaker, other metal (e.g. shrapnel or surgical prostheses) or paramagnetic objects contained within the * Medicinal patch that cannot be removed for the scans.

What they're measuring

GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy

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).

Trial details

NCT IDNCT03336398

SponsorNew York State Psychiatric Institute

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-06-17

Results submitted2025-03-31

View on ClinicalTrials.gov More Tinnitus trials