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

October 23, 2023 updated by: Rachel Fremont, Icahn School of Medicine at Mount Sinai

KET-MCI: An Open-label Trial of Single-dose Ketamine Treatment to Improve Depression in Mild Cognitive Impairment

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Ketamine is a rapid-acting antidepressant thought to work, at least in part, by the enhancement of neural plasticity and the growth of new synapses. 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 individuals with 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, they 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. A key hypothesis of this study is that IV ketamine treatment will be well-tolerated and will improve depression and cognition in patients with MCI-D. The effects of brain imaging and activity abnormalities and amyloid biomarker status on the responsiveness to ketamine will be explored. This open-label pilot study is designed to gather data to support an application for a larger NIH-funded study.

This study is an open-label trial to determine the safety and tolerability of a single sub-anesthetic (0.5 mg/kg) intravenous (IV) ketamine treatment in individuals with mild cognitive impairment and depression (MCI-D). As secondary endpoints, whether treatment with a single dose of ketamine may improve mood or cognition in individuals with MCI-D will be examined. In exploratory analyses, whether AD biomarker status has any influence on the effectiveness of ketamine treatment in MCI and brain connectivity changes after ketamine treatment will be examined. The entire study period will be approximately 1 month from start to finish. The study begins with screening followed by a baseline visit. Then there will be a single visit where an infusion of 0.5 mg/kg of IV ketamine will be performed. There will be follow-up visits 1 day, 2 days, 3 days, 7 days, and one month after the infusion. Baseline visit will include questionnaires, blood draw, cognitive evaluation, clinical evaluation, neuroimaging (specifically a non-contrast magnetic resonance image (MRI)), and an optional electroencephalogram (EEG). Follow-ups will include questionnaires, cognitive evaluation, and clinical evaluation. Additionally, blood draw and imaging (MRI) follow-up may be performed.

Study Type

Interventional

Enrollment (Estimated)

15

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School of Medicine at Mount Sinai (Depression and Anxiety Center)
        • Contact:
        • Principal Investigator:
          • Rachel Fremont

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Single dose of IV ketamine administered at the standard dose used for depression treatment (0.5 mg/kg)
Drug: IV Ketamine
0.5 mg/kg IV Ketamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number and severity of symptom events as assessed by the Patient Rated Inventory of Side Effects (PRISE)
Time Frame: end of study, at 1 month
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)
Time Frame: end of study, at 1 month
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
Time Frame: end of study, at 1 month
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Depressive symptoms as assessed with the Montgomery-Asberg Depression Rating Scale (MADRS)
Time Frame: end of study, at 1 month
The number of depressive symptoms will be assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). The Montgomery Asberg Depression Rating Scale (MADRS-S) has 10-items which are based on mood symptoms over the past 7 days. Each items is scored 0 (normal) to 6 (severe depression) with overall score ranges from 0 (normal) to 60 (severe depression)
end of study, at 1 month
Level of cognition as assessed with the NIH Toolbox Cognition Battery
Time Frame: end of study, at 1 month
The NIH Toolbox Cognition Battery (NIHTB-CB) is a 30 minute long cognitive evaluation consisting of 7 tests done via iPad that has been developed to allow for quick and robust measurement of multiple cognitive domains including executive function, memory, language, and processing speed using a series of well-validated assessments. Scoring for the NIH Toolbox Cognition Battery is automated and individuals are assigned a T-score (mean = 50, SD = 10) representing their cognitive performance compared to age, education, gender, and ethnicity-matched peers.
end of study, at 1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Icahn School of Medicine at Mount Sinai

Investigators

  • Principal Investigator: Rachel Fremont, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2023

Primary Completion (Estimated)

December 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

September 29, 2023

First Submitted That Met QC Criteria

September 29, 2023

First Posted (Actual)

October 6, 2023

Study Record Updates

Last Update Posted (Actual)

October 25, 2023

Last Update Submitted That Met QC Criteria

October 23, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • STUDY-23-00160

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All of the individual participant data collected during the trial where participant has consented to have data shared, after de-identification will be shared.

IPD Sharing Time Frame

Immediately following publication and ending 5 years following article publication.

IPD Sharing 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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