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

NCT06069843 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY-23-00160
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Depression; Mild Cognitive Impairment

Keywords

Depression; Mild Cognitive Impairment; Intravenous Ketamine; Cognition; Neuroplasticity; Geriatric Psychiatry

Outcome Measures

Primary Outcomes (3)

• Number and severity of symptom events as assessed by the Patient Rated Inventory of Side Effects (PRISE)

  Number of symptom events as assessed by the patient in a self-report measure. PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other)

  end of study, at 1 month

• Severity of symptom events as assessed by the Patient Rated Inventory of Side Effects (PRISE)

  Severity of symptom events as assessed by the patient in a self-report measure. PRISE assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other)

  end of study, at 1 month

• Frequency of symptoms measured using PRISE

  Frequency of observed adverse events as captured by the PRISE; assesses the presence of treatment side effects in nine organ/function systems (gastrointestinal, nervous system, heart, eyes/ears, skin, genital/urinary, sleep, sexual functioning, and other)

  end of study, at 1 month

Secondary Outcomes (2)

• Number of Depressive symptoms as assessed with the Montgomery-Asberg Depression Rating Scale (MADRS)

  end of study, at 1 month

• Level of cognition as assessed with the NIH Toolbox Cognition Battery

  end of study, at 1 month

Study Arms (1)

Treatment

EXPERIMENTAL

Single dose of IV ketamine administered at the standard dose used for depression treatment (0.5 mg/kg)

Drug: IV Ketamine

Interventions

IV Ketamine DRUG

0.5 mg/kg IV Ketamine

Treatment

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai (Depression and Anxiety Center)

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

Depression; Cognitive Dysfunction

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Rachel Fremont, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

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: Assistant Professor

Study Record Dates

• First Submitted: September 29, 2023
• First Posted: October 6, 2023
• Study Start: November 1, 2024
• Primary Completion: September 1, 2025
• Study Completion: September 1, 2025
• Last Updated: January 29, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication and ending 5 years following article publication.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee identified for this purpose. Proposals should be directed to Rachel.fremont@mssm.edu, data requestors will need to sign a data access agreement.

Locations

US (1)