Single-dose Ketamine Treatment to Improve Depression in Mild Cognitive Impairment

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Ketamine is a NMDA-receptor antagonist that promotes synapse formation and has been shown to rapidly improve symptoms in depression. Even a single dose of ketamine has been shown to improve depression and cognition with short-term memory, inhibitory control, cognitive flexibility, and processing speed showing improvements within days of treatment. The mechanism behind ketamine's rapid action is not clear but some groups have speculated it may be related to enhanced neuroplasticity, particularly in the frontal areas and the hippocampus. If this mechanism is accurate, ketamine may be especially effective in treating mild cognitive impairment and depression (MCI-D) where changes in the hippocampus and frontal areas have been implicated. Although few studies have been published on the effects of ketamine in older adults, some small pilot studies suggest that ketamine treatment might be effective in improving depression in older adults and relatively safe. There are no studies looking at the effects of ketamine treatment in patients with MCI-D. The research team hypothesize that IV ketamine treatment will be well-tolerated and will improve depression and cognition in patients with MCI-D. The study team will explore the effects of brain imaging abnormalities and amyloid biomarker status on the responsiveness to ketamine. The study team will conduct an open-label pilot study designed to gather data to support an application for a larger NIH-funded study.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Icahn School of Medicine at Mount Sinai
• Treatments: Ketamine

Criteria

Inclusion Criteria:

• Age 50-90

• Able to give consent

• Montgomery Asberg Depression Rating Scale (MADRS) score of ≥20 consistent with at least "moderate depression"

• Clinical diagnosis of mild cognitive impairment or mild Alzheimer's Disease

Exclusion Criteria:

• Serious unstable medical illness

• Uncontrolled hypertension

• Abnormal electrocardiogram

• Renal impairment defined as BUN 20 mg/dl and/or creatinine clearance >1.3

• Current drug or alcohol use disorder

• History of seizures without a clear or resolved etiology

• Lifetime history of schizophrenia, schizoaffective disorder, or bipolar 1 or 2 disorder

• Montreal Cognitive Assessment (MoCA) score <18

• Presence of psychotic symptoms or lifetime psychotic disorder

• Recreational ketamine or phencyclidine use in the last 2 years

• BMI>40

• Serious or imminent suicidal or homicidal risk

• Systolic blood pressure >165 or diastolic blood pressure >95 on infusion day