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

Sponsor

Icahn School of Medicine at Mount Sinai (Other)

Overall Status

Recruiting

CT.gov ID

NCT06069843

Collaborator

(none)

Enrollment

Location

Arm

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Depression Mild Cognitive Impairment	Drug: IV Ketamine	Phase 2

Detailed Description

This protocol will allow for careful psychiatric and medical screening of patients and healthy volunteers (1) to examine potential patterns in symptom presentation (at a group level) towards the development of new theories of mood and anxiety disorders; (2) to determine if they are appropriate for participation in research protocols in the Depression and Anxiety Center (DAC) at Icahn School of Medicine at Mount Sinai (IMSSM). Because DAC focuses on a specific range of mood and anxiety disorders, should subjects be declared ineligible for any DAC studies after this initial assessment (for example, due to presence of substance dependence, a psychotic disorder, or autism), participation will be terminated and the subject will not complete the remaining screening. Data collected through this screening protocol will be used for analysis in assessing patterns of symptoms among individuals with varying levels of anxiety and depression, and may be used for future studies within DAC, the latter with the subject's informed consent.

Research Question: The specific aim of this study is to characterize and diagnose subjects with mood and anxiety disorders, chronic medical conditions with known psychiatric comorbidity, and healthy volunteers for (1) pattern characterization and theory generation; (2) potential eligibility for DAC studies. This is considered to be a screening protocol where psychiatric and medical information will be collected to determine whether a subject is appropriate for IRB approved DAC protocols. It is also, however, a data collection protocol, in that participants who potentially meet criteria for our studies are providing valuable information that can be used to inform our understanding of mood and anxiety disorders.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Oct 1, 2023

Anticipated Primary Completion Date :

Dec 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Number and severity of symptom events as assessed by the Patient Rated Inventory of Side Effects (PRISE) [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)
Severity of symptom events as assessed by the Patient Rated Inventory of Side Effects (PRISE) [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)
Frequency of symptoms measured using PRISE [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)

Secondary Outcome Measures

Number of Depressive symptoms as assessed with the Montgomery-Asberg Depression Rating Scale (MADRS) [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)
Level of cognition as assessed with the NIH Toolbox Cognition Battery [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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