Phase 2 trial of ketamine for tinnitus in 42 adults did not report main results

Status: COMPLETED | Phase: PHASE2 Condition(s): Tinnitus Intervention(s): Ketamine Hydrochloride in saline (DRUG) 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 Detailed: Tinnitus has a prevalence of approximately 1 in 10 adults in the United States. Among those with tinnitus, 36% had nearly constant symptoms and almost 30% of those report that their tinnitus as a big or a very big problem. Currently there are few effective treatments for tinnitus, and no approved medications. Cognitive behavioral and retraining therapy provide some relief, but many patients fail to respond. Animal research and human studies indicate that maladaptive plasticity plays a role in tinnitus, which involves glutamatergic signaling largely at the NMDA and AMPA receptors. Additionally, GABA signaling has been shown to be impaired in tinnitus. Rodent models show a diminished sensitivity to GABA signaling and human magnetic resonance spectroscopy (MRS) studies show decreased GABA le Primary Outcome(s): GABA and Glutamate (Glx) Levels in the Auditory Cortex Derived From 3T Magnetic Resonance Spectroscopy Enrollment: 42 (ACTUAL) Lead Sponsor: New York State Psychiatric Institute Start: 2019-09-01 | Primary Completion: 2023-06-17 Results posted: 2026-03-25