Investigation of the NMDA Antagonist Ketamine as a Treatment for Tinnitus

NCT03336398 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 7432W81XWH1810221
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Tinnitus

Outcome Measures

Primary Outcomes (1)

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

  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.

  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).

Study Arms (1)

Tinnitus Patients

EXPERIMENTAL

Tinnitus patients with symptoms over 6 months duration. 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.

Drug: Ketamine Hydrochloride in saline

Interventions

Ketamine Hydrochloride in saline DRUG

0.5 mg/kg IV of ketamine hydrochloride in saline will be administered with one of the MRS Scan

Also known as: Ketamine HCI

Tinnitus Patients

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• New York State Psychiatric Institute: lead

Study Sites (1)

1051 Riverside Drive

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Tinnitus

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Hearing Disorders; Ear Diseases; Otorhinolaryngologic Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Diana Martinez
• Organization: NYPInstitute

dm437@cumc.columbia.edu

646-774-6160

Study Officials

• Diana Martinez

  NYSPI/Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Medical Doctor

Study Record Dates

• First Submitted: November 6, 2017
• First Posted: November 8, 2017
• Study Start: September 1, 2019
• Primary Completion: June 17, 2023
• Study Completion: July 1, 2024
• Last Updated: March 25, 2026
• Results First Posted: March 25, 2026

Record last verified: 2026-03

Locations

US (1)