DepressionPhase 2NCT02106325
Ketamine as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients
A Phase 2 study testing Ketamine and Diphenhydramine in people with Depression, run by NYU Langone Health at 2 sites in United States.
Trial summary
Investigators will conduct a trial to evaluate the use of Ketamine as an alternate treatment for people with Major Depressive Disorder. This study plans to explore the potential that Ketamine's rapid antidepressant action holds for improving outcomes in patients presenting to the Emergency Department with severe… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Depression
- What is being tested?
- Ketamine and Diphenhydramine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2013to Mar 2017
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Medically stable as determined by the medical physician
- Meets criteria for Major Depressive Disorder (MDD) based on a structured clinical Interview (MINI International Neuropsychiatric Interview).
- Reports symptoms of severe depression at the time of presentation, defined as a score of 24 or greater on the MADRS.
- Patients for whom a psychiatric evaluation and disposition decision has been made by emergency psychiatry staff to admit to an inpatient psychiatric unit at Bellevue Hospital Center or NYU Tisch Hospital.
- Each subject must have a level of understanding sufficient to sign an informed consent stating that the treatment being offered is not FDA approved for the treatment of depression and is being provided as an off-label option.
Who cannot join
- Pregnancy
- Inability to read or understand English
- Current clinical signs of intoxication or delirium at time of study intervention
- Overdose, within previous 24 hours, of any agent which would impair ketamine metabolism
- Lifetime misuse/abuse of ketamine, phencyclidine (PCP),or related substances
- Lifetime history of psychotic spectrum illness
Show all 22Show fewer
- First-degree relative with history of psychotic illness
- Lifetime diagnosis of borderline personality disorder, or as confirmed by assessment using items #90-104 of the SCID-II (for DSM-IV).
- Subjects with clinically significant abnormal findings as determined by medical history, physical examination, vital signs (blood pressure, heart rate, and respiration rate), O2 saturation measure, 12-lead ECG, clinical laboratory tests (CBC, chemistry panel, thyroid function tests), urine drug screen, and urine pregnancy test (for females of childbearing potential only).
- Clinically unstable medical, surgical or neurological conditions at ED presentation
- History of stroke or intracranial hypertension
- History of glaucoma
- Subjects with one or more seizures without a clear and resolved etiology
- Current NMDA antagonist medications (eg. Amantadine, Rimantadine, Lamotrigine, Memantine, Dextromethorphan)
- Known hypersensitivity to ketamine or amantadine
- Anti-psychotic medications (Typicals or Atypicals), with the exception of low-dose quetiapine (total daily dose of 100mg or less).
- Actively trying to commit suicide, even in a hospital setting
- Current homicide risk
- Unable or unwilling to give informed consent according to HIC guidelines
- Unable or unwilling to provide 2 contact phone numbers or be followed up per study protocol.
- Previous enrollment in this study.
- Concurrent enrollment in a research protocol investigating experimental pharmacologic treatments for depression at this or any other institution.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Bellevue Hospital Center
New York, New York, 10016
NYU Langone Medical Center/Tisch Hospital
New York, New York, 10016
About this study
Official title: A Randomized, Double-Blinded Controlled Trial of an N-Methyl D-Aspartate Antagonist as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients
Investigators will conduct a trial to evaluate the use of Ketamine as an alternate treatment for people with Major Depressive Disorder. This study plans to explore the potential that Ketamine's rapid antidepressant action holds for improving outcomes in patients presenting to the Emergency Department with severe depression. Since this is a controlled trial we will use an IV of Ketamine or and equivalent volume of Diphenhydramine. Subjects will be randomly assigned to receive Ketamine or Benadryl. Investigators will then compare measures of mood pre- and post-infusion in the Emergency Department. To supplement self-reported measures of depressive symptoms(e.g. mood), investigators will obtain objective measures of the biological aspects of Major Depressive Disorder.
Read the detailed description
To explore the use of ketamine as a potential rapidly-acting antidepressant (RAA) for Emergency Department (ED) patients with major depressive disorder (MDD).
Investigators will conduct a randomized controlled study to evaluate the rapidity and persistence of antidepressant effects of a single sub-anesthetic dose of intravenous (IV) ketamine (0.25mg/kg) or an equivalent volume of diphenhydramine (25mg) delivered IV over 1-2 minutes, by comparing measures of mood pre- and post-infusion in Emergency Department (ED) patients with MDD. Subjects will be randomly assigned (1:1) to receive a bolus of ketamine or diphenhydramine. To supplement self-reported measures of depressive symptoms (e.g., mood, suicidal ideation, etc.), investigators will obtain objective measures of heart rate and heart rate variability, measure serum levels of the pro- and anti-inflammatory cytokines (interleukin IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and tissue necrosis factor, TNF-α), which have been shown to play an important role in stress, depression and suicidal behavior. In addition, investigators will obtain serum levels of brain derived neurotrophic factor (BDNF) because reduced serum BDNF has been described during acute depressive episodes in patients with MDD, with reports of rescue effects following treatment with various antidepressants and with ketamine (Aydemir 2005, Gervasoni 2005, Karege 2002, Karege 2005, Duncan 2013, Shimizu 2003). Investigators will also measure serum magnesium levels, as these have been shown to correlate in a predictive manner with response to conventional antidepressants (Camardese 2012), and there are data to suggest that ketamine's efficacy in treatment-resistant depression could be related to a relative magnesium deficiency in such patients (Murck 2013).
This study will allow investigators to determine to what extent low-dose ketamine, an N-Methyl-D-Aspartate (NMDA) antagonist, achieves a rapid reduction in symptoms for severely depressed ED patients with or without suicidal ideation. For decades, much higher doses of IV ketamine (1-2mg/kg) have been used routinely in the ED as a dissociative anesthetic (Green 2011). In 2011, an open-label study was the first published of the use of low dose ketamine (0.2mg/kg), administered by rapid intravenous infusion, in the ED setting for acutely depressed patients which demonstrated its feasibility, safety, preliminary efficacy and acceptability to both ED patients and staff (Larkin 2011). One long-term goal of this research is to expand treatment options available to depressed ED patients that mitigate the need for inpatient admission and serve as a safety bridge to future out-patient treatment for major depression. As an adjunct to standard treatment, low-dose NMDA receptor antagonists have the potential to positively impact: ED waiting times; repeat visits to the ED; short-term risk of suicide attempts; length of stay on inpatient units and the need for hospital admissions for many acutely depressed patients.
- Conditions
- Depression
- Being tested
- Ketamine, Diphenhydramine
- Keywords
- Ketamine, Ketlar, Depression, Antidepressants, Treatment, Acute
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Other names for ketamine: ketalar
IV of Ketamine (.25mg/kg)
DiphenhydramineDrug
Also called Other names for diphenhydramine: benadryl
Intravenous Diphenhydramine (25mg) at the time of presentation to Emergency Department
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | IV Ketamine .25mg/kg Receives: Drug: Ketamine |
| Diphenhydramine | Placebo comparator | 25mg Diphenhydramine Receives: Drug: Diphenhydramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale
40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points.
0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
Measured: Baseline and 16 weeks
Beck Depression Inventory-II (BDI-II)
BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.
0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
Measured: 120 min post-infusion
Hamilton Depression Scale (Ham-D)
Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2.
Sum the scores from the first 17 items 0-7= Normal 8-13= Mild Depression 14-18= Moderate Depression 19-22= Severe Depression >23= Very Severe Depression
Measured: 4-6 hours post-infusion
Secondary outcomes (6)
Change in Treatment Alliance Score
The I-TAS is a 10-item, Likert-style rating scale designed to assess a patient's composite treatment alliance as it develops across multi-disciplinary treatment components. The I-TAS was intended to measure the primary alliance factors identified by Hatcher and Barends (1996) of bond, goals and collaboration. Each question is scored on a scale of 0 (Completely False) to 6 (Completely True). Total scores on the ITAS range from 0 to 60, with higher scores representing greater alliance with the treatment team (better outcome). The reported score is an average of each participant's total score on the ITAS.
Measured: Baseline and 16 weeks
Beck Scale for Suicidal Ideation (BSSI)
BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63.
0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
Measured: 40 minutes post-infusion
Montgomery-Åsberg Depression Rating Scale Suicide Ideation Item (MADRS-SI)
40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points.
0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
Measured: 40 minutes post-infusion
Length of Inpatient Stay
Measured: 2 Weeks Post-infusion
Outpatient Follow-up Compliance
Scoring System: 0= not compliant, 1=compliant
Measured: 1 Day
Inpatient Treatment Alliance Scale (ITAS)
The I-TAS is a 10-item, Likert-style rating scale designed to assess a patient's composite treatment alliance as it develops across multi-disciplinary treatment components. The I-TAS was intended to measure the primary alliance factors identified by Hatcher and Barends (1996) of bond, goals and collaboration. Each question is scored on a scale of 0 (Completely False) to 6 (Completely True). Total scores on the ITAS range from 0 to 60, with higher scores representing greater alliance with the treatment team (better outcome). The reported score is an average of each participant's total score on the ITAS.
Measured: 7 days post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2014 (estimated)
- Study startDec 2013
- Primary completionFeb 2016
- Study completionMar 2017
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 NYU Langone HealthThe 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Stephen Ross, MD, Principal investigator, NYU Langone HealthK. Casey Paleos, MD, Study chair, New York Unversity School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02106325
- Sponsor's protocol ID
- 13-00794
- Status last verified
- Aug 2018
- First submitted
- 12 Dec 2013
- Last updated
- 14 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blinded Controlled Trial of an N-Methyl D-Aspartate Antagonist as a Rapidly-Acting Antidepressant in Depressed Emergency Department Patients
- ClinicalTrials.gov ID
- NCT02106325
- Acronym / sponsor ID
- 13-00794
- Conditions
- Depression
- Keywords
- Ketamine, Ketlar, Depression, Antidepressants, Treatment, Acute
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Study start
- Dec 2013
- Primary completion
- Feb 2016 (actual)
- Study completion
- Mar 2017 (actual)
- First posted
- 8 Apr 2014 (estimated)
- Results
- Posted 14 Sep 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators will conduct a trial to evaluate the use of Ketamine as an alternate treatment for people with Major Depressive Disorder. This study plans to explore the potential that Ketamine's rapid antidepressant action holds for improving outcomes in patients presenting to the Emergency Department with severe depression. Since this is a controlled trial we will use an IV of Ketamine or and equivalent volume of Diphenhydramine. Subjects will be randomly assigned to receive Ketamine or Benadryl. Investigators will then compare measures of mood pre- and post-infusion in the Emergency Department. To supplement self-reported measures of depressive symptoms(e.g. mood), investigators will obtain objective measures of the biological aspects of Major Depressive Disorder.
Detailed description
To explore the use of ketamine as a potential rapidly-acting antidepressant (RAA) for Emergency Department (ED) patients with major depressive disorder (MDD).
Investigators will conduct a randomized controlled study to evaluate the rapidity and persistence of antidepressant effects of a single sub-anesthetic dose of intravenous (IV) ketamine (0.25mg/kg) or an equivalent volume of diphenhydramine (25mg) delivered IV over 1-2 minutes, by comparing measures of mood pre- and post-infusion in Emergency Department (ED) patients with MDD. Subjects will be randomly assigned (1:1) to receive a bolus of ketamine or diphenhydramine. To supplement self-reported measures of depressive symptoms (e.g., mood, suicidal ideation, etc.), investigators will obtain objective measures of heart rate and heart rate variability, measure serum levels of the pro- and anti-inflammatory cytokines (interleukin IL-1, IL-2, IL-6, IL-8, IL-10, IL-12, and tissue necrosis factor, TNF-α), which have been shown to play an important role in stress, depression and suicidal behavior. In addition, investigators will obtain serum levels of brain derived neurotrophic factor (BDNF) because reduced serum BDNF has been described during acute depressive episodes in patients with MDD, with reports of rescue effects following treatment with various antidepressants and with ketamine (Aydemir 2005, Gervasoni 2005, Karege 2002, Karege 2005, Duncan 2013, Shimizu 2003). Investigators will also measure serum magnesium levels, as these have been shown to correlate in a predictive manner with response to conventional antidepressants (Camardese 2012), and there are data to suggest that ketamine's efficacy in treatment-resistant depression could be related to a relative magnesium deficiency in such patients (Murck 2013).
This study will allow investigators to determine to what extent low-dose ketamine, an N-Methyl-D-Aspartate (NMDA) antagonist, achieves a rapid reduction in symptoms for severely depressed ED patients with or without suicidal ideation. For decades, much higher doses of IV ketamine (1-2mg/kg) have been used routinely in the ED as a dissociative anesthetic (Green 2011). In 2011, an open-label study was the first published of the use of low dose ketamine (0.2mg/kg), administered by rapid intravenous infusion, in the ED setting for acutely depressed patients which demonstrated its feasibility, safety, preliminary efficacy and acceptability to both ED patients and staff (Larkin 2011). One long-term goal of this research is to expand treatment options available to depressed ED patients that mitigate the need for inpatient admission and serve as a safety bridge to future out-patient treatment for major depression. As an adjunct to standard treatment, low-dose NMDA receptor antagonists have the potential to positively impact: ED waiting times; repeat visits to the ED; short-term risk of suicide attempts; length of stay on inpatient units and the need for hospital admissions for many acutely depressed patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineIV Ketamine .25mg/kg |
| Diphenhydramine | Placebo comparator | Drug: Diphenhydramine25mg Diphenhydramine |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Medically stable as determined by the medical physician
- Meets criteria for Major Depressive Disorder (MDD) based on a structured clinical Interview (MINI International Neuropsychiatric Interview).
- Reports symptoms of severe depression at the time of presentation, defined as a score of 24 or greater on the MADRS.
- Patients for whom a psychiatric evaluation and disposition decision has been made by emergency psychiatry staff to admit to an inpatient psychiatric unit at Bellevue Hospital Center or NYU Tisch Hospital.
- Each subject must have a level of understanding sufficient to sign an informed consent stating that the treatment being offered is not FDA approved for the treatment of depression and is being provided as an off-label option.
Key exclusion criteria (22 listed)
- Pregnancy
- Inability to read or understand English
- Current clinical signs of intoxication or delirium at time of study intervention
- Overdose, within previous 24 hours, of any agent which would impair ketamine metabolism
- Lifetime misuse/abuse of ketamine, phencyclidine (PCP),or related substances
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 |
|---|---|---|
| KetamineAlso: Other names for ketamine: ketalarIV of Ketamine (.25mg/kg) | Drug | Ketamine |
| DiphenhydramineAlso: Other names for diphenhydramine: benadrylIntravenous Diphenhydramine (25mg) at the time of presentation to Emergency Department | Drug | Diphenhydramine |
Primary outcome
Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale
Time frame: Baseline and 16 weeks
40 Minutes Post Infusion, The MADRS-S instrument has nine questions, with an overall score ranging from 0 to 54 points. 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression.
Beck Depression Inventory-II (BDI-II)
Time frame: 120 min post-infusion
BDI-II items are rated on a 4-point scale ranging from 0 to 3 based on severity of each item. The maximum total score is 63. 0-13 Indicates minimal depression 14-19 Indicates mild depression 20-28 Indicates Moderate depression 29-63 Indicates Severe depression
Hamilton Depression Scale (Ham-D)
Time frame: 4-6 hours post-infusion
Although the HAM-D form lists 21 items, the scoring is based on the first 17. It generally takes 15-20 minutes to complete the interview and score the results. Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Sum the scores from the first 17 items 0-7= Normal 8-13= Mild Depression 14-18= Moderate Depression 19-22= Severe Depression >23= Very Severe Depression
6 secondary outcomes
Change in Treatment Alliance Score
Time frame: Baseline and 16 weeks
Beck Scale for Suicidal Ideation (BSSI)
Time frame: 40 minutes post-infusion
Montgomery-Åsberg Depression Rating Scale Suicide Ideation Item (MADRS-SI)
Time frame: 40 minutes post-infusion
Length of Inpatient Stay
Time frame: 2 Weeks Post-infusion
Outpatient Follow-up Compliance
Time frame: 1 Day
Inpatient Treatment Alliance Scale (ITAS)
Time frame: 7 days post-infusion
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Depression
Recruiting
Unified Protocol in Penitentiary Facilities
Depression Disorders, Anxiety
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
Not yet recruitingObservational study
Functional Impact of Psychological Symptoms in Patients With Superior Semicircular Canal Dehiscence Syndrome (SSCD): a National Cross-sectional Study
Superior Semicircular Canal Dehiscence
Recruiting
Trial Phase: Syndemic Adapted Medly Uganda
Mental Health
Recruiting
Cultural Adaptation of an Online Parenting Intervention to Reduce the Risk of Depression and Anxiety in Adolescents
Risk of Depression and Anxiety
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.
Stephen Ross, MD principal investigator
NYU Langone Health
K. Casey Paleos, MD study chair
New York Unversity School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketamine and Diphenhydramine in people with Depression, run by NYU Langone Health at 2 sites 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 5 inclusion and 22 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: finished, as of the sponsor's last update on 14 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 14 Sep 2018). 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?
Evaluate the Effects of Ketamine on Depressive Symptomatology by Measuring Change in Score on the Montgomery-Asberg Depressive Rating Scale (time frame: Baseline and 16 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 14 Sep 2018.