DepressionPhase 2NCT01312844
A Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)
A Phase 2 study testing Scopolamine in people with Depression, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
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: 1. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Depression
- What is being tested?
- Scopolamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Jul 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Males and females between the ages of 18-50 (inclusive)
- DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features, and a HAM-D-17 score of 18 or higher
- Female subjects must be postmenopausal, surgically sterile, or, if of child-bearing age, using double-barrier contraceptive method or prescription oral contraceptives (e.g. estrogen-progestin combinations), contraceptive implants (e.g. NorplantTM, DepoProveraTM, or transdermally delivered contraceptives (Ortho EvraTM) before entry and throughout the study; and have a negative urine b-HCG pregnancy test at screening.
Who cannot join
- Substance use disorder active use within the last 6 months (per assessment using SCID)
- Organic mental disorders
- Seizure disorders
- Unstable physical disorder or physical disorder judged to significantly affect the central nervous system function
- Heart block
- Pre-existing sick-sinus
Show all 24Show fewer
- Chronic treatment with beta blockers
- Any cardiac arrhythmia
- Hypotension
- Coronary artery disease
- Liver and renal function impairment
- Urge incontinence or prostatic hypertrophy
- Colitis
- Crohn's disease
- GI motility disorders
- Asthma
- COPD
- Treatment with anti-cholinergic and cholinomimetic medications
- Contraindications to scopolamine including hypersensitivity to scopolamine, other belladonna alkaloids, and/or any component of the formulation
- Wide and narrow angle glaucoma
- Acute hemorrhage
- Paralytic ileus
- Myasthenia gravis
- Patients on belladonna, belladonna alkaloids, cisapride, or potassium chloride
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02144
About this study
Official title: A Pilot Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)
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:
- Patients receiving ECT plus scopolamine will have greater improvement in depression symptoms than those receiving ECT plus placebo.
- Patients receiving scopolamine in addition to ECT will require fewer ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.
- Time to response and to remission in the scopolamine group will be significantly shorter compared to ECT alone.
Read the detailed description
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.
- Conditions
- Depression
- Being tested
- Scopolamine
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ScopolamineDrug
Those receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT
| Study group | Role | What they receive |
|---|---|---|
| Scopolamine | Experimental | Patients receiving IV scopolamine at ECT treatment Receives: Drug: Scopolamine |
| Placebo | Placebo comparator | Patients receiving IV placebo at ECT treatment Receives: Drug: Scopolamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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. .
Measured: 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.
Measured: Duration of ECTtreatment (usually 2 weeks)
Secondary outcomes (6)
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.
Measured: Duration of ECT treatment (usually 2 weeks)
The Mean Number of Moderate to Severe Side Effects
The mean number of adverse events classified as moderate to severe.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Duration of ECT treatment (usually 2 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Mar 2011 (estimated)
- Study startApr 2010
- Primary completionJul 2012
- Study completionJul 2012
Why it stopped: This was an inpatient study, but PI left inpatient service at MGH
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John D. Matthews, Massachusetts General Hospital
- Investigators
- John D Matthews, MD, Principal investigator, Massachusetts General HospitalDavid Abramson, MD, Principal investigator, Massachusetts General HospitalMaurizio Fava, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01312844
- Sponsor's protocol ID
- 2009P002288
- Status last verified
- Apr 2017
- First submitted
- 4 May 2010
- Last updated
- 30 May 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study of the Use of IV Scopolamine to Augment the Efficacy of Electroconvulsive Therapy (ECT)
- ClinicalTrials.gov ID
- NCT01312844
- Acronym / sponsor ID
- 2009P002288
- Conditions
- Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: This was an inpatient study, but PI left inpatient service at MGH
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 11 Mar 2011 (estimated)
- Results
- Posted 18 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Patients receiving ECT plus scopolamine will have greater improvement in depression symptoms than those receiving ECT plus placebo.
- Patients receiving scopolamine in addition to ECT will require fewer ECT treatments to obtain response/remission compared to the group receiving ECT plus placebo.
- Time to response and to remission in the scopolamine group will be significantly shorter compared to ECT alone.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Scopolamine | Experimental | Drug: ScopolaminePatients receiving IV scopolamine at ECT treatment |
| Placebo | Placebo comparator | Drug: ScopolaminePatients receiving IV placebo at ECT treatment |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Males and females between the ages of 18-50 (inclusive)
- DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features, and a HAM-D-17 score of 18 or higher
- Female subjects must be postmenopausal, surgically sterile, or, if of child-bearing age, using double-barrier contraceptive method or prescription oral contraceptives (e.g. estrogen-progestin combinations), contraceptive implants (e.g. NorplantTM, DepoProveraTM, or transdermally delivered contraceptives (Ortho EvraTM) before entry and throughout the study; and have a negative urine b-HCG pregnancy test at screening.
Key exclusion criteria (24 listed)
- Substance use disorder active use within the last 6 months (per assessment using SCID)
- Organic mental disorders
- Seizure disorders
- Unstable physical disorder or physical disorder judged to significantly affect the central nervous system function
- Heart block
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 |
|---|---|---|
| ScopolamineThose receiving active drug will receive scopolamine 4mcg/kg IV with each treatment, until completion of ECT | Drug | Placebo, Scopolamine |
Primary outcome
Change in Ham D 17 Scores
Time frame: At the time of ECT completion (about 2 weeks)
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.
Time to Response for Patients Receiving ECT
Time frame: Duration of ECT treatment (usually 2 weeks)
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. .
Number of ECT Treatments Received to Achieve Response/Remission
Time frame: Duration of ECTtreatment (usually 2 weeks)
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.
6 secondary outcomes
Number of ECT Treatments Withheld Due to Cognitive Impairment
Time frame: Duration of ECT treatment (usually 2 weeks)
The Mean Number of Moderate to Severe Side Effects
Time frame: Duration of ECT treatment (usually 2 weeks)
The Mean Levels of Physiological Measures of ECT (Blood Pressure)
Time frame: Duration of ECT treatment (usually 2 weeks)
The Mean Levels of Physiological Measures of ECT (Heart Rate)
Time frame: Duration of ECT treatment (usually 2 weeks)
The Mean Levels of Physiological Measures of ECT (Seizure Duration)
Time frame: Duration of ECT treatment (usually 2 weeks)
The Mean Levels of Physiological Measures of ECT (Energy Needed)
Time frame: Duration of ECT treatment (usually 2 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
John D Matthews, MD principal investigator
Massachusetts General Hospital
David Abramson, MD principal investigator
Massachusetts General Hospital
Maurizio Fava, MD principal investigator
Massachusetts General Hospital
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 Scopolamine in people with Depression, run by Massachusetts General Hospital 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 3 inclusion and 24 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: stopped early, as of the sponsor's last update on 30 May 2017. 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. Some participants in this study may receive a placebo. 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?
Yes. Results are posted in the registry (first posted 18 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Ham D 17 Scores (time frame: At the time of ECT completion (about 2 weeks)). 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 30 May 2017.