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In this proof of concept study, the investigators plan to administer iv ketamine interleaved with ECT days.
Patients with treatment resistant depression who are deemed to be eligible for ECT treatment will randomly be assigned to either ketamine or active placebo.
The study will compare the effects of standard ketamine dosing with an active placebo arm.
Hypothesis 1:
The investigators hypothesize that interleaved Electroconvulsive Treatment and active ketamine treatment will lead to a meaningful clinical improvement compared to Electroconvulsive Treatment and placebo treatment arm.
Hypothesis 2:
The investigators hypothesize that interleaved Electroconvulsive Treatment and active ketamine treatment will attenuate cognitive side effects.
Methods and Design:
Patients with treatment resistant depression who are deemed to be eligible for Electroconvulsive Treatment will randomly be assigned to either ketamine or active placebo
Electroconvulsive Treatments:
All patients (independent of their depression scores) will receive the same Electroconvulsive Treatment parameters: Bi-frontal brief pulse (0.5 miliseconds) Electroconvulsive Treatment administered by using Thymatron Electroconvulsive Treatment machine.
Study blinding:
Neither the patients, nor the treating psychiatrist or the nurse will be aware of the patient's assigned arm. The success of blinding will be tested after each ketamine treatment with a questionnaire given to the subject, raters, and treating physician.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine Infusions | Experimental | Subjects who are randomized to be on this group will receive a standard dose of ketamine interleaved with Electroconvulsive Treatments. |
|
| Midazolam | Active Comparator | Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | inter venous injections |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Hamilton Depression Rating Scale (HAMD-17) at Last Infusion | Change in HAMD-17 at Infusion 6. Scores range from 0 to 50, with higher scores representing more depression. | visit 17 |
| Montgomery Asberg Depression Rating Scale (MADRS) at Last Infusion | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 | visit 17 |
| Measure | Description | Time Frame |
|---|---|---|
| Montreal Cognitive Assessment (MOCA) at Last Infusion | MoCA scores range between 0 and 30. Higher scores reflect higher cognition. | visit 17 |
| Hopkins Verbal Learning Test - Revised (HVLT-R) at Last Infusion |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Murat Altinay, MD | The Cleveland Clinic | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Cleveland Clinic Foundation Center for Behavioral Health | Cleveland | Ohio | 44195 | United States |
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15 patients with TRD, who were referred to the Cleveland Clinic outpatient depression clinic or ECT service, were recruited in the study. 3 subjects were lost prior to randomization. 2 subjects were lost to follow up after the screening visit, and 1 subject withdrew consent after the baseline visit.12 patients were included in the final analysis.
Patients with TRD who are admitted to the inpatient psychiatric to receive an acute series of ECT will randomly be assigned to one of the study arms.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine Infusions | Subjects who are randomized to be on this group will receive a standard dose of ketamine alternated with Electroconvulsive Treatments. Ketamine: intervenous injections |
| FG001 | Midazolam | Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments. Midazolam: intervenous injections |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Ketamine Infusions | Subjects who are randomized to be on this group will receive a standard dose of ketamine interleaved with Electroconvulsive Treatments. Ketamine: intervenous injections |
| BG001 | Midazolam |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Hamilton Depression Rating Scale (HAMD-17) at Last Infusion | Change in HAMD-17 at Infusion 6. Scores range from 0 to 50, with higher scores representing more depression. | Analysis was performed on all patients using a mixed effect model. Maximum likelihood estimation allowed for inclusion of all patients, even when loss to follow-up or remission occurred. | Posted | Mean | Standard Error | score on a scale | visit 17 |
|
3 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ketamine Infusions | Subjects who are randomized to be on this group will receive a standard dose of ketamine alternated with Electroconvulsive Treatments. Ketamine: intervenous injections |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal Thoughts | Psychiatric disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| MURAT ALTINAY, MD | CLEVELAND CLINIC FOUNDATION | 2164453359 | altinam@ccf.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jan 12, 2016 | Jun 24, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D061218 | Depressive Disorder, Treatment-Resistant |
| D003865 | Depressive Disorder, Major |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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| Midazolam | Drug | inter venous injections |
|
|
The number of words remembered are recorded. Scores range from 0 to 12 with higher scores reflecting better acquisition.
| visit 17 |
| Controlled Oral Word Association Test (COWAT) at Last Infusion | This is a verbal fluency measure. Outcome is the count of words that meet criteria within 1 minute, so the minimum is 0 and no fixed maximum exists. Higher scores reflect a better outcome. | visit 17 |
| Responder Rate on HAMD-17 by Last Infusion | Count of the patients who showed response (>50% decrease). | visit 17 |
Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments.
Midazolam: intervenous injections
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments.
Midazolam: intervenous injections
|
|
|
| Primary | Montgomery Asberg Depression Rating Scale (MADRS) at Last Infusion | Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60 | Analysis was performed using mixed effect models. Maximum likelihood estimation allowed inclusion of all patients in analysis. | Posted | Mean | Standard Error | score on a scale | visit 17 |
|
|
|
|
| Secondary | Montreal Cognitive Assessment (MOCA) at Last Infusion | MoCA scores range between 0 and 30. Higher scores reflect higher cognition. | Analysis was performed on all patients using a mixed effect model. Maximum likelihood estimation allowed for inclusion of all patients, even when loss to follow-up or remission occurred. | Posted | Mean | Standard Error | score on a scale | visit 17 |
|
|
|
|
| Secondary | Hopkins Verbal Learning Test - Revised (HVLT-R) at Last Infusion | The number of words remembered are recorded. Scores range from 0 to 12 with higher scores reflecting better acquisition. | Analysis was performed on all patients using a mixed effect model. Maximum likelihood estimation allowed for inclusion of all patients, even when loss to follow-up or remission occurred. | Posted | Mean | Standard Error | score on a scale | visit 17 |
|
|
|
|
| Secondary | Controlled Oral Word Association Test (COWAT) at Last Infusion | This is a verbal fluency measure. Outcome is the count of words that meet criteria within 1 minute, so the minimum is 0 and no fixed maximum exists. Higher scores reflect a better outcome. | Analysis was performed on all patients using a mixed effect model. Maximum likelihood estimation allowed for inclusion of all patients, even when loss to follow-up or remission occurred. | Posted | Mean | Standard Error | number of words | visit 17 |
|
|
|
|
| Secondary | Responder Rate on HAMD-17 by Last Infusion | Count of the patients who showed response (>50% decrease). | Posted | Count of Participants | Participants | visit 17 |
|
|
|
|
| 0 |
| 7 |
| 0 |
| 7 |
| 1 |
| 7 |
| EG001 | Midazolam | Subjects who are randomized to be on this group will receive midazolam infusions interleaved with Electroconvulsive Treatments. Midazolam: intervenous injections | 0 | 5 | 0 | 5 | 0 | 5 |
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| D001519 |
| Behavior |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |