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This was an inpatient study, but PI left inpatient service at MGH
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The primary purpose of this study is to assess the ability of scopolamine to improve the antidepressant effects of ECT and to determine whether scopolamine will shorten the time to response and remission for patients receiving ECT.
The hypothesis are:
Electroconvulsive therapy (ECT) is a highly effective treatment for severe major depression. It has been estimated that approximately 10 percent of all patients admitted to the hospital for treatment of major depressive disorder receive ECT.
However, not all patients who receive ECT respond, and of those who do, not all achieve remission. Furthermore, while there is a wide range in the number of ECT treatments done among all people with depression, the average is approximately eight treatments. Because treatments are usually done three times per week (Monday, Wednesday, and Friday), the minimal length of stay for the average person receiving inpatient ECT is typically greater than two weeks.
Finally, ECT is not without risk, and every round of ECT incurs additional risk of not just the treatment itself, but also the risks of general anesthesia. Thus, although ECT is a robust mode of treatment for Major Depressive Disorder (MDD), there remains a need for improved treatment efficacy and speed of onset. Improving the efficacy of ECT would not only benefit individuals with MDD, but also have far-reaching effects for the health care system as it could impact the cost and resources utilized.
Ideally, an agent could be added to augment the effect of ECT, both in terms of efficacy as well as speed of onset. In 2006, Furrey et al, reported the rapid antidepressant effect of the antimuscarinic drug, scopolamine, delivered parenterally. Significant antidepressant effect was found after the first scopolamine administration. The improvement was reported immediately following the first IV administration, increased across all treatments, and was sustained into the placebo crossover period.
Scopolamine is an anticholinergic muscarinic agent, with activity in the CNS and pilot data to suggest a significant impact on rapidly improving depressive symptoms in patient with MDD, when administered IV. Thus, it serves as a reasonable choice to augment the effects of ECT in the treatment of patients with MDD.
Primary Aim 1) Assess the ability of scopolamine to augment the antidepressant effects of ECT.
Hypothesis 1a: Patients receiving ECT plus scopolamine will have significantly greater mean improvement on total HAM-D score between baseline and endpoint than those receiving ECT plus placebo.
Hypothesis 1b: Patients receiving scopolamine in addition to ECT will require fewer mean ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.
Primary Aim 2) Evaluate the hypothesis that scopolamine will shorten the time to response and remission for patients receiving ECT.
Hypothesis 2: Time to response and to remission in the Scopolamine group will be significantly shorter compared to ECT alone.
Secondary Aim: Provide evidence for the tolerability of intravenous scopolamine administered during ECT.
Hypothesis 3a: There will be no between group difference (between ECT plus scopolamine vs ECT plus placebo) in mean number of ECT sessions withheld due to cognitive impairment (as determined by attending psychiatrist).
Hypothesis 3b: There will be no between group differences (between ECT plus scopolamine vs ECT plus placebo) with regards to the mean number of moderate to severe side effects.
Hypothesis 3c: There will be no significant difference between the scopolamine plus ECT group and the placebo plus ECT group on mean levels of physiological measures of ECT including: heart rate, blood pressure, seizure length, duration of muscle paralysis, duration of asystole, and energy need to induce seizure.
Exploratory Analyses: we will assess whether the scopolamine plus ECT group will have a shorter average length of stay on the inpatient psychiatric unit compared to those receiving ECT plus placebo.
We will also assess whether the scopolamine plus ECT group will have significant differences in the cognitive measures at endpoint compared to those receiving ECT plus placebo.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Scopolamine | Experimental | Patients receiving IV scopolamine at ECT treatment |
|
| Placebo | Placebo Comparator | Patients receiving IV placebo at ECT treatment |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Scopolamine | Drug | Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in Ham D 17 Scores | Change in Ham D 17 scores measured by the difference between baseline HAM D score and HAM D score at last ECT administration. The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. A negative change score refers to a decrease in HAM D score, while a positive change score would refer to an increase in HAM D score. | At the time of ECT completion (about 2 weeks) |
| Time to Response for Patients Receiving ECT | The number of days between baseline HAM D score and HAM D score showing response (defined as a HAM D score less than half of baseline). If patients HAM D score rose above this marker at any point in the study, they were not considered as responding.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. . | Duration of ECT treatment (usually 2 weeks) |
| Number of ECT Treatments Received to Achieve Response/Remission | The number of ECT treatments needed to achieve response (defined as a HAM D score less than half of baseline) and remission (defined as a HAM D score of less than 8). If patients HAM D score rose above these markers at any point in the study, they were not considered as responding or remitting.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. | Duration of ECTtreatment (usually 2 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of ECT Treatments Withheld Due to Cognitive Impairment | The number of ECT treatments withheld during the course of the study due to cognitive impairment. In these cases, the participant would still be enrolled in the study but have a reduced # of ECTs. This outcome measure does not include patients who withdrew from the study. | Duration of ECT treatment (usually 2 weeks) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| John D Matthews, MD | Massachusetts General Hospital | Principal Investigator |
| David Abramson, MD | Massachusetts General Hospital | Principal Investigator |
| Maurizio Fava, MD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Boston | Massachusetts | 02144 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Scopolamine | Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT |
| FG001 | Placebo | Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Scopolamine | Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT |
| BG001 | Placebo |
| 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 | Change in Ham D 17 Scores | Change in Ham D 17 scores measured by the difference between baseline HAM D score and HAM D score at last ECT administration. The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. A negative change score refers to a decrease in HAM D score, while a positive change score would refer to an increase in HAM D score. | Posted | Mean | Standard Deviation | units on a scale | At the time of ECT completion (about 2 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 | Scopolamine | Patients receiving IV scopolamine at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Recent memory loss | Nervous system disorders |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Deja vu / confusion | Psychiatric disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. John Matthews | Massachusetts General Hospital | 617-643-9095 | jmatthews@partners.org |
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| ID | Term |
|---|---|
| D003863 | Depression |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D012601 | Scopolamine |
| ID | Term |
|---|---|
| D012602 | Scopolamine Derivatives |
| D014326 | Tropanes |
| D053961 | Azabicyclo Compounds |
| D001372 | Aza Compounds |
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| The Mean Number of Moderate to Severe Side Effects | The mean number of adverse events classified as moderate to severe. | Duration of ECT treatment (usually 2 weeks) |
| The Mean Levels of Physiological Measures of ECT (Blood Pressure) | Blood pressure was taken immediately post ECT administration at each ECT visit. We averaged Blood pressure for each participant at each ECT administration. The reported mean refers to the average among all participants in each group. | Duration of ECT treatment (usually 2 weeks) |
| The Mean Levels of Physiological Measures of ECT (Heart Rate) | Heart rate was taken immediately post ECT administration at each ECT visit. We averaged heart rate for each participant at each ECT administration. The reported mean refers to the average among all participants in each group. | Duration of ECT treatment (usually 2 weeks) |
| The Mean Levels of Physiological Measures of ECT (Seizure Duration) | Mean duration in seconds of the seizure induced by ECT for each participant at each ECT administration they received.The reported mean refers to the average among all participants in each group. | Duration of ECT treatment (usually 2 weeks) |
| The Mean Levels of Physiological Measures of ECT (Energy Needed) | Mean energy needed to induce the seizure for each participant at each ECT administration they received. The reported mean refers to the average among all participants in each group. | Duration of ECT treatment (usually 2 weeks) |
Patients receiving IV placebo at ECT treatment
Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Patients receiving IV placebo at ECT treatment
Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
|
|
| Primary | Time to Response for Patients Receiving ECT | The number of days between baseline HAM D score and HAM D score showing response (defined as a HAM D score less than half of baseline). If patients HAM D score rose above this marker at any point in the study, they were not considered as responding.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. . | Only 3 (out of 4) Scopolamine patients and 2 (out of 3) placebo patients reached response | Posted | Mean | Standard Deviation | days | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| Primary | Number of ECT Treatments Received to Achieve Response/Remission | The number of ECT treatments needed to achieve response (defined as a HAM D score less than half of baseline) and remission (defined as a HAM D score of less than 8). If patients HAM D score rose above these markers at any point in the study, they were not considered as responding or remitting.The HAM D 17 measures severity of depression with 52 being most severe and 0 being no depression. | Only 3 (out of 4) Scopolamine patients and 2 (out of 3) placebo patients reached response and remission. | Posted | Mean | Standard Deviation | # of ECT administrations | Duration of ECTtreatment (usually 2 weeks) |
|
|
|
| Secondary | Number of ECT Treatments Withheld Due to Cognitive Impairment | The number of ECT treatments withheld during the course of the study due to cognitive impairment. In these cases, the participant would still be enrolled in the study but have a reduced # of ECTs. This outcome measure does not include patients who withdrew from the study. | Posted | Mean | Standard Deviation | ECT Treatments withheld | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| Secondary | The Mean Number of Moderate to Severe Side Effects | The mean number of adverse events classified as moderate to severe. | Posted | Mean | Standard Deviation | number of side effects | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| Secondary | The Mean Levels of Physiological Measures of ECT (Blood Pressure) | Blood pressure was taken immediately post ECT administration at each ECT visit. We averaged Blood pressure for each participant at each ECT administration. The reported mean refers to the average among all participants in each group. | Missing vitals forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group | Posted | Mean | Standard Deviation | mmHg | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| Secondary | The Mean Levels of Physiological Measures of ECT (Heart Rate) | Heart rate was taken immediately post ECT administration at each ECT visit. We averaged heart rate for each participant at each ECT administration. The reported mean refers to the average among all participants in each group. | Missing vitals forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group | Posted | Mean | Standard Deviation | Beats per minute | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| Secondary | The Mean Levels of Physiological Measures of ECT (Seizure Duration) | Mean duration in seconds of the seizure induced by ECT for each participant at each ECT administration they received.The reported mean refers to the average among all participants in each group. | Missing ECT forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group | Posted | Mean | Standard Deviation | seconds | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| Secondary | The Mean Levels of Physiological Measures of ECT (Energy Needed) | Mean energy needed to induce the seizure for each participant at each ECT administration they received. The reported mean refers to the average among all participants in each group. | Missing ECT forms for one participant in Scopolamine group (n=4), only reported data for 3 participants in Scopolamine group | Posted | Mean | Standard Deviation | joules | Duration of ECT treatment (usually 2 weeks) |
|
|
|
| 1 |
| 4 |
| 1 |
| 4 |
| EG001 | Placebo | Patients receiving IV placebo at ECT treatment Scopolamine: Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT | 0 | 3 | 1 | 3 |
| Agitation requiring restraint | Psychiatric disorders |
|
| Hypoxia event | Respiratory, thoracic and mediastinal disorders |
|
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| D009930 |
| Organic Chemicals |
| D001533 | Belladonna Alkaloids |
| D012991 | Solanaceous Alkaloids |
| D000470 | Alkaloids |
| D006571 | Heterocyclic Compounds |
| D019086 | Bridged Bicyclo Compounds, Heterocyclic |
| D006572 | Heterocyclic Compounds, Bridged-Ring |