A Phase 4 interventional study of ketamine and IV Saline in Major Depressive Disorder, sponsored by Massachusetts General Hospital. Terminated at 1 site in United States. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2017-05-22.
Sponsored by Massachusetts General Hospital · Phase 4, Interventional, and Treatment
Electroconvulsive therapy (ECT), is considered the most effective treatment for severe treatment resistant major depressive disorder (MDD), but it requires about 3 weeks of treatments and can cause considerable acute deficits in memory. It would be a major advance in treatment if ECT could work faster with fewer treatments and result in decrease incidence of memory problems. Ketamine is an excellent candidate for augmentation of ECT because of its acute effects on depression, its short half-life, and its safety profile when given at low doses. Ketamine is given as an infusion and could easily be incorporated into the routine management of patients undergoing ECT, but has never been evaluated prospectively in this context.
The investigators propose to assess the efficacy, feasibility, tolerability and safety of N-methyl-D-aspartate antagonist augmentation of ECT using ketamine.
Aim #1: To assess the efficacy of ketamine augmentation in reducing time to remission of a major depressive episode (MDE).
Aim #2: To assess the efficacy of ketamine augmentation on ECT-related cognitive side effects.
Aim #3: To assess the feasibility, safety, and tolerability of ketamine augmentation of ECT.
Exploratory aim #4: We propose to assess the patterns of functional connectivity before, during and after ECT using standard clinical EEG to better characterize the effect of ECT and to correlate clinical effects with changes in EEG measurements.
Thirty (30) participants will be recruited over 24 months. Participants will be males and females, ages 18-60, with severe MDD (baseline score HAM_D-28 >= 20) deemed appropriate for ECT treatment by their treating physician, agreeing to receive ECT treatment as part of their clinical care, and able to provide informed consent.
Exclusion criteria are any other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia, any history of psychosis, substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence, organic mental disorders, seizure disorder or chronic antiepileptic medications, severe or unstable medical illness, pregnancy.
Study procedures: eligible patients will be randomized to a double-blind administration of ketamine (0.5 mg/kg) or saline before the first three ECT treatments. Right Unilateral ECT (RUL-ECT) will be administered at 6 times the seizure threshold, using the d'Elia placement of the electrodes. Electroconvulsive therapy will be given 3 times per week, as per standard of care at MGH. Depression severity will be assessed weekly with the HAM-D 28 (the main outcome measure), administered by a clinician blinded to randomization.
The neuropsychological assessment battery is designed to include instruments sensitive to the cognitive impairment associated with depression in general and ECT treatment in particular will be repeated at baseline, at the end of acute treatment series and at 3 months follow-up.
Also patients will undergo repeated EEG monitoring, at baseline after one week of treatment and at follow up with the aim of possibly identifying EEG features associated with response.
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Exclusion Criteria:
ketamine (0.5 mg/kg) followed by anesthetic agent titrated to sedation and succinylcholine titrated to muscle relaxation Right unilateral ECT at 5-6x seizure threshold three times a week
Drug: ketamine · Procedure: ECT · Drug: Muscle Relaxant · Drug: Anesthetic Agents
IV saline, followed by anesthestic agent titrated to sedation and succinylcholine titrated to muscle relaxation. Right unilateral ECT at 5-6x seizure threshold three times a week
Other: IV Saline · Procedure: ECT · Drug: Muscle Relaxant · Drug: Anesthetic Agents
eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care
eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care
ECT will be administered as per standard of care
All participant will receive routine course of muscle relaxant with ECT as per standard of care
All participant will receive routine course of anesthetic agents with ECT as per standard of care
Change in Hamilton Depression Rating Scale - 28
HAMD will be administered at every ECT treatment.The HAM D 28 is a 28 item scale with scores ranging from 0 to 83, with 0 being no depression and 83 being high levels of depression symptoms. The change in HAM S score was determined by the difference of the HAM D score at the last ECT administration and the baseline HAM D score. A negative change score reflects a decreased HAM D score between the first and last ECT administration and therefore a reduction in depressive symptoms.
Time frame: baseline, one month
Number of Participants With Cognitive Side Effects
will compare the incidence of participants with memory deficits between groups, as determined by incidents of clinician reported cognitive adverse events
Time frame: 3 months
| Milestone | Ketamine | Placebo |
|---|---|---|
| Started | 8 | 9 |
| Completed | 6 | 8 |
| Not completed | 2 | 1 |
HAMD will be administered at every ECT treatment.The HAM D 28 is a 28 item scale with scores ranging from 0 to 83, with 0 being no depression and 83 being high levels of depression symptoms. The change in HAM S score was determined by the difference of the HAM D score at the last ECT administration and the baseline HAM D score. A negative change score reflects a decreased HAM D score between the first and last ECT administration and therefore a reduction in depressive symptoms.
| units on a scale | Ketamine | Placebo |
|---|---|---|
| Change in Hamilton Depression Rating Scale - 28 | -17.50 ± 6.53 | -14.00 ± 14.20 |
will compare the incidence of participants with memory deficits between groups, as determined by incidents of clinician reported cognitive adverse events
| Participants | Ketamine | Placebo |
|---|---|---|
| Number of Participants With Cognitive Side Effects | 0 | 1 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ketamine | 0/6 (0%) | 0/6 (0%) | 2/6 (33.3%) |
| Placebo | 0/8 (0%) | 1/8 (12.5%) | 3/8 (37.5%) |
| Event | Ketamine | Placebo |
|---|---|---|
| Racing ThoughtsPsychiatric disorders | 0/6 | 1/8 |
| Body painMusculoskeletal and connective tissue disorders | 0/6 | 1/8 |
| Event | Ketamine | Placebo |
|---|---|---|
| Jaw painMusculoskeletal and connective tissue disorders | 1/6 | 0/8 |
| Numbness in feet and bodyNervous system disorders | 1/6 | 0/8 |
| Heart pounding/tightness in chestCardiac disorders | 1/6 | 0/8 |
| Tingling in feetNervous system disorders | 1/6 | 0/8 |
| AnxietyPsychiatric disorders | 1/6 | 0/8 |
| Fluid in right earEar and labyrinth disorders | 0/6 | 1/8 |
| SedationPsychiatric disorders | 0/6 | 1/8 |
| FatigueGeneral disorders | 0/6 | 1/8 |
| Short term memory impairmentNervous system disorders | 0/6 | 1/8 |
| AgitationPsychiatric disorders | 0/6 | 1/8 |
| Age, Categorical(Participants) | Ketamine | Placebo | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 6 | 7 | 13 |
| >=65 years | 0 | 1 | 1 |
| Age, Continuous(years) | Ketamine | Placebo | Total |
|---|---|---|---|
| Mean | 41.43 ± 15.62 | 48.75 ± 12.22 | 48.57 ± 13.20 |
| Sex: Female, Male(Participants) | Ketamine | Placebo | Total |
|---|---|---|---|
| Female | 4 | 7 | 11 |
| Male | 2 | 1 | 3 |
| Region of Enrollment(participants) | Ketamine | Placebo | Total |
|---|---|---|---|
| United States | 6 | 8 | 14 |
This study is terminated, as verified in Apr 2017. You cannot join it, but the record below documents what was studied.
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Massachusetts General Hospital