DepressionPhase 2NCT06069843
Single-dose Ketamine Treatment to Improve Depression in Mild Cognitive Impairment
A Phase 2 study testing IV Ketamine in people with Depression and Mild Cognitive Impairment, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Depression, Mild Cognitive Impairment
- What is being tested?
- IV Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2024to Sep 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Icahn School of Medicine at Mount Sinai (Depression and Anxiety Center)
New York, New York, 10029
About this study
Official title: 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.
Read the 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.
- Conditions
- Depression, Mild Cognitive Impairment
- Being tested
- IV Ketamine
- Keywords
- Depression, Mild Cognitive Impairment, Intravenous Ketamine, Cognition, Neuroplasticity, Geriatric Psychiatry
- Medical subject headings
- Depression, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IV KetamineDrug
0.5 mg/kg IV Ketamine
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Single dose of IV ketamine administered at the standard dose used for depression treatment (0.5 mg/kg) Receives: Drug: IV Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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)
Measured: 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)
Measured: end of study, at 1 month
Secondary outcomes (2)
Number of Depressive symptoms as assessed with the Montgomery-Asberg Depression Rating Scale (MADRS)
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)
Measured: end of study, at 1 month
Level of cognition as assessed with the NIH Toolbox Cognition Battery
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.
Measured: end of study, at 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2023
- Study start1 Nov 2024
- Primary completionSep 2025 (estimated)
- Study completionSep 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rachel Fremont, Icahn School of Medicine at Mount Sinai
- Investigators
- Rachel Fremont, MD, PhD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06069843
- Sponsor's protocol ID
- STUDY-23-00160
- Status last verified
- Jan 2025
- First submitted
- 29 Sep 2023
- Last updated
- 29 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All of the individual participant data collected during the trial where participant has consented to have data shared, after de-identification will be shared.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- KET-MCI: An Open-label Trial of Single-dose Ketamine Treatment to Improve Depression in Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT06069843
- Acronym / sponsor ID
- STUDY-23-00160
- Conditions
- Depression, Mild Cognitive Impairment
- Keywords
- Depression, Mild Cognitive Impairment, Intravenous Ketamine, Cognition, Neuroplasticity, Geriatric Psychiatry
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Sep 2025 (estimated)
- First posted
- 6 Oct 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: IV KetamineSingle dose of IV ketamine administered at the standard dose used for depression treatment (0.5 mg/kg) |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| IV Ketamine0.5 mg/kg IV Ketamine | Drug | Treatment |
Primary outcome
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)
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)
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)
2 secondary outcomes
Number of Depressive symptoms as assessed with the Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: 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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jan 2025.
- Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial where participant has consented to have data shared, after de-identification will be shared.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rachel Fremont, MD, PhD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing IV Ketamine in people with Depression and Mild Cognitive Impairment, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2025.