DepressionSURE-ECTNCT05137938
Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders)
A study testing Intranasal Ketamine (IN) in people with Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Despite the known efficacy of pharmacotherapy (i.e. antidepressants) and psychotherapeutic interventions in treating depressive disorders, research evidence suggests that 20% to 40% of patients with major depressive disorder (MDD) do not respond adequately to such treatments. Read more about this study
- Who is it for?
- Ages 21 to 65 years
- Conditions the study is for
- Depression
- What is being tested?
- Intranasal Ketamine (IN)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteCanada
- Study dates
- 25 Oct 2021to 24 Jul 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 21 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals with a diagnosis of non-psychotic MDD as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
- Individuals meeting criteria for Ultra Resistant Major Depressive Disorder (URD) in current episode
- URD is defined as:
- those who received at least eight convulsive therapy treatment sessions and did not respond, or
- those who were not able to tolerate convulsive therapy
- Individuals scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
- Individuals capable to provide consent who are receiving care as outpatients
Who cannot join
- Individuals with history of substance use disorder (i.e. dependence or abuse) within the past month; and lifetime history of ketamine substance use disorder as confirmed by the MINI
- Concomitant major unstable medical illness such as poorly controlled high blood pressure or patients diagnosed with enlarged prostate or reporting any other urinary related issues
- Pregnancy or the intention to become pregnant and breastfeeding during the study as confirmed by self-report. Female participants of reproductive potential must be willing to use a medically acceptable method of birth control which include highly effective (e.g. approved hormonal contraceptives, intrauterine device, tubal ligation) or double barrier (e.g. male condom with diaphragm, male condom with cervical cap) methods of contraception or abstinence if that is the usual and preferred lifestyle of the participant
- Presence of cardiac decompensation/heart failure v)
- Diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder (current) as confirmed by the MINI
- Diagnosis of severe personality disorder as assessed during the initial consultation with a physician at the Temerty Centre prior to study entry
Show all 14Show fewer
- Any significant neurological disorder (e.g., a space occupying brain lesion, a history of stroke, a cerebral aneurysm, a seizure disorder, Parkinson's disease, Huntington's chorea, multiple sclerosis) as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
- Individuals presenting with a medical condition, a medication, or a laboratory abnormality that could cause a major depressive episode or significant cognitive impairment in the opinion of the investigator
- Individuals requiring a benzodiazepine with a dose equivalent to lorazepam 2 mg/day or higher; being on any anticonvulsant(e.g. Lamotrigine) and/or opioid medication due to the potential of these medications to limit the efficacy of ketamine
- Individuals unable to communicate in spoken and written English fluently enough to complete the required study assessments due to a language barrier or a non-correctable clinically significant sensory impairment (i.e., cannot hear or see well enough to complete clinical assessments)
- Individuals with cognitive or physical impairment which may potentially interfere with IN ketamine administration and subject's ability to stay in the same place for a 2-hr monitoring supervision as assessed through medical history review during the initial consultation with a physician at the Temerty Centre prior to study entry
- Any intracranial implant (e.g., aneurysm clips, shunts, cochlear implants) or any other metal object within or near the head, excluding the mouth, that cannot be safely removed given that we will be using TMS-EMG/EEG
- Those unable to secure escort to accompany them back home after ketamine sessions will also be excluded from this study
- Any known allergy to the study medication or any component/ingredient of the ketamine preparation
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Clinical Effects of Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders). Pilot Study
Despite the known efficacy of pharmacotherapy (i.e. antidepressants) and psychotherapeutic interventions in treating depressive disorders, research evidence suggests that 20% to 40% of patients with major depressive disorder (MDD) do not respond adequately to such treatments. These patients are diagnosed with Treatment-Resistant Depression (TRD), and are sometimes treated with convulsive therapy. However, about 10-30% of TRD patients do not respond to convulsive therapy, and are thus diagnosed with Ultra-Resistant Depression (URD). Using an open label pilot study involving subjects, this trial aims to assess the safety, tolerability, and clinical effects of intranasal ketamine (IN) treatment in patients who do not respond to convulsive therapy. Intranasal ketamine (IN) treatment approach has shown promising therapeutic outcomes for patients with TRD, but has not yet been studied on patients with URD.
Read the detailed description
Ketamine is a fast-acting anesthetic that can have stimulant effects when taken at low doses. It acts as a non-competitive high-affinity N-methyl-d-aspartate (NMDA) receptor antagonist that stimulates synaptic glutamate release and blocks extra-synaptic NMDA receptors. This mechanism of action mediates excitatory synaptic transmission through the central nervous system and therefore results in robust antidepressant effects. Administering intravenous (IV) ketamine to patients with TRD has shown to produce rapid antidepressant effects. Nevertheless, delivering IV ketamine to patients can be challenging since it requires specialized expertise and equipment. A promising alternative that preserves IV ketamine's rapid onset of therapeutic action while minimizing inconvenience and discomfort is intranasal drug delivery (IN). This current proof-of-concept clinical trial is an open label pilot study on patients with treatment-resistant unipolar depression who did not respond to, or did not tolerate, an acute course of convulsive therapy. Using a combination of Transcranial Magnetic Stimulation (TMS) neurophysiological tools with electromyography (EMG) and electroencephalography (EEG), this trial also aims to explore biomarkers of ketamine's antidepressant effect by examining ketamine's action on NMDA neurotransmission. Investigating the impact of ketamine on cortical excitation and inhibition could provide insight into the role of NMDA receptors in cortical physiology, and therefore determine potential predictors of clinical response for depression.
Objective 1: To test the safety and tolerability of IN ketamine in patients with URD who did not respond to/tolerate an acute course of convulsive therapy
Hypothesis 1: IN ketamine will be safe and well tolerated in patients with URD
Objective 2: To test the clinical effects of IN ketamine patients with URD who did not respond to/tolerate an acute course of convulsive therapy
Hypothesis 2: IN ketamine will result in improvement in depressive symptoms, suicidal ideation, and quality of life measures (compared to scores from baseline)
Objective 3: To investigate the impact of ketamine on cortical excitation via intracortical facilitation (ICF) and cortical inhibition via short-interval cortical inhibition (SICI) paradigms
Hypothesis 3: IN ketamine will result in neurophysiological changes as measured by TMS-EMG and EEG
- Conditions
- Depression
- Being tested
- Intranasal Ketamine (IN)
- Keywords
- Convulsive therapy, Open-label trial, Pilot study, Treatment-resistant depression (TRD), Ketamine, Intranasal drug delivery (IN), N-methyl-d-aspartate (NMDA), Receptor antagonist, Transcranial magnetic stimulation (TMS), Electromyography (EMG), Electroencephalography (EEG), Intracortical facilitation (ICF), Short-interval cortical inhibition (SICI), Electroconvulsive Therapy (ECT)
- Medical subject headings
- Depression, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intranasal Ketamine (IN)Drug
A sterile form of ketamine will be administered intranasally twice weekly for four weeks. Dosing schedule will be determined based on patient's weight using a specialized formula. Patients will be started at the lowest dose during the first treatment session. Dose will be titrated further to therapeutic dose in the following sessions. The dose will be adjusted if patients do not tolerate full therapeutic doses. After receiving the second treatment of each week, participants will be seen by a study physician to determine dosing for the following week. Patients will be monitored by trained personnel for the full duration of the 2 hour supervision period. Vital signs and physical symptoms will be monitored consistently and measurements taken every 30 minutes. Appropriate medications will be provided to manage treatment-related side effects and any adverse events. Labetalol will be used in the management of treatment-related transient hypertension as needed.
| Study group | Role | What they receive |
|---|---|---|
| Intranasal Ketamine (IN) | Experimental | Ketamine will be administered intranasally (IN) using an atomizer (MAD300 by Teleflex, North Carolina, USA). Receives: Drug: Intranasal Ketamine (IN) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in symptom severity of depression as measured by the Hamilton Rating Scale for Depression - 24
Hamilton Rating Scale for Depression (24-item version); This scale is used to quantify the severity of symptoms of depression Scale range: 0-76 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome)
Measured: 2 months
Secondary outcomes (7)
Change in symptom severity of Suicidal Ideation as measured by by the Scale of Suicide Ideation (SSI)
Scale for Suicide Ideation (SSI); This scale is used to assess the presence or absence of suicidal ideation and the degree of severity of suicidal ideas Scale range: 0-38 (total score) Lower scores indicate lower severity of suicidal ideation (i.e., better outcome) Higher scores indicate higher severity of suicidal ideation (i.e., worse outcome)
Measured: 2 months
Safety and tolerability as assessed by changes in Blood Pressure (BP)
Assessed through monitoring of systolic and diastolic Blood Pressure (mmHg) on each treatment session before treatment and every 30 minutes within a 2-hour monitoring period.
Measured: 1 month
Safety and tolerability as assessed by changes in Heart Rate (BPM)
Assessed through monitoring of Heart Rate (beats per minute) on each treatment session before treatment and every 30 minutes within a 2-hour monitoring period.
Measured: 1 month
Safety and tolerability as assessed by changes in O2 Saturation
Assessed through monitoring of Oxygen saturation levels on each treatment session before treatment and every 30 minutes within a 2-hour monitoring period.
Measured: 1 month
Safety and Tolerability of IN Ketamine as assessed by monitoring of adverse events
Assessed through monitoring of adverse events, cardiovascular adverse events and/or respiratory distress throughout the trial.
Measured: 2 months
Impact of Ketamine on cortical excitation as measured by intracortical facilitation (ICF)
Assessed through administration of neurophysiological paradigms using Transcranial Magnetic Stimulation (TMS) paired with electromyography (EMG) and electroencephalography (EEG).
Measured: 1 months
Impact of Ketamine on cortical inhibition as measured by short-interval cortical inhibition (SICI)
Assessed through administration of neurophysiological paradigms using Transcranial Magnetic Stimulation (TMS) paired with electromyography (EMG) and electroencephalography (EEG).
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2021
- Study start25 Oct 2021
- Primary completion24 Jul 2023
- Study completion24 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Open label pilot study
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yuliya Knyahnytska, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05137938
- Sponsor's protocol ID
- 095-2019
- Acronym
- SURE-ECT
- Status last verified
- Aug 2023
- First submitted
- 2 Nov 2021
- Last updated
- 14 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Knyahnytska Y, Zomorrodi R, Kaster T, Voineskos D, Trevizol A, Blumberger D. The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial. JMIR Res Protoc. 2022 Jan 17;11(1):e30163. doi: 10.2196/30163.
PubMed 34882570
Study at a glance
From the registry record, last updated by the sponsor on 14 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Clinical Effects of Intranasal Ketamine in Ultra-REsistant Depression (SURE-ECT Non Responders). Pilot Study
- ClinicalTrials.gov ID
- NCT05137938
- Acronym / sponsor ID
- SURE-ECT / 095-2019
- Conditions
- Depression
- Keywords
- Convulsive therapy, Open-label trial, Pilot study, Treatment-resistant depression (TRD), Ketamine, Intranasal drug delivery (IN), N-methyl-d-aspartate (NMDA), Receptor antagonist
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 25 Oct 2021 (actual)
- Primary completion
- 24 Jul 2023 (actual)
- Study completion
- 24 Jul 2023 (actual)
- First posted
- 30 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Despite the known efficacy of pharmacotherapy (i.e. antidepressants) and psychotherapeutic interventions in treating depressive disorders, research evidence suggests that 20% to 40% of patients with major depressive disorder (MDD) do not respond adequately to such treatments. These patients are diagnosed with Treatment-Resistant Depression (TRD), and are sometimes treated with convulsive therapy. However, about 10-30% of TRD patients do not respond to convulsive therapy, and are thus diagnosed with Ultra-Resistant Depression (URD). Using an open label pilot study involving subjects, this trial aims to assess the safety, tolerability, and clinical effects of intranasal ketamine (IN) treatment in patients who do not respond to convulsive therapy. Intranasal ketamine (IN) treatment approach has shown promising therapeutic outcomes for patients with TRD, but has not yet been studied on patients with URD.
Detailed description
Ketamine is a fast-acting anesthetic that can have stimulant effects when taken at low doses. It acts as a non-competitive high-affinity N-methyl-d-aspartate (NMDA) receptor antagonist that stimulates synaptic glutamate release and blocks extra-synaptic NMDA receptors. This mechanism of action mediates excitatory synaptic transmission through the central nervous system and therefore results in robust antidepressant effects. Administering intravenous (IV) ketamine to patients with TRD has shown to produce rapid antidepressant effects. Nevertheless, delivering IV ketamine to patients can be challenging since it requires specialized expertise and equipment. A promising alternative that preserves IV ketamine's rapid onset of therapeutic action while minimizing inconvenience and discomfort is intranasal drug delivery (IN). This current proof-of-concept clinical trial is an open label pilot study on patients with treatment-resistant unipolar depression who did not respond to, or did not tolerate, an acute course of convulsive therapy. Using a combination of Transcranial Magnetic Stimulation (TMS) neurophysiological tools with electromyography (EMG) and electroencephalography (EEG), this trial also aims to explore biomarkers of ketamine's antidepressant effect by examining ketamine's action on NMDA neurotransmission. Investigating the impact of ketamine on cortical excitation and inhibition could provide insight into the role of NMDA receptors in cortical physiology, and therefore determine potential predictors of clinical response for depression.
Objective 1: To test the safety and tolerability of IN ketamine in patients with URD who did not respond to/tolerate an acute course of convulsive therapy
Hypothesis 1: IN ketamine will be safe and well tolerated in patients with URD
Objective 2: To test the clinical effects of IN ketamine patients with URD who did not respond to/tolerate an acute course of convulsive therapy
Hypothesis 2: IN ketamine will result in improvement in depressive symptoms, suicidal ideation, and quality of life measures (compared to scores from baseline)
Objective 3: To investigate the impact of ketamine on cortical excitation via intracortical facilitation (ICF) and cortical inhibition via short-interval cortical inhibition (SICI) paradigms
Hypothesis 3: IN ketamine will result in neurophysiological changes as measured by TMS-EMG and EEG
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Open label pilot study
| Arm | Type | Receives |
|---|---|---|
| Intranasal Ketamine (IN) | Experimental | Drug: Intranasal Ketamine (IN)Ketamine will be administered intranasally (IN) using an atomizer (MAD300 by Teleflex, North Carolina, USA). |
Who may qualify
- Ages
- 21 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Individuals with a diagnosis of non-psychotic MDD as confirmed by the Mini-International Neuropsychiatric Interview (MINI)
- Individuals meeting criteria for Ultra Resistant Major Depressive Disorder (URD) in current episode
- Individuals scoring 14 and above on the Hamilton Rating Scale for Depression-24 Items (HRSD-24)
- Individuals capable to provide consent who are receiving care as outpatients
Key exclusion criteria (14 listed)
- Individuals with history of substance use disorder (i.e. dependence or abuse) within the past month; and lifetime history of ketamine substance use disorder as confirmed by the MINI
- Concomitant major unstable medical illness such as poorly controlled high blood pressure or patients diagnosed with enlarged prostate or reporting any other urinary related issues
- Pregnancy or the intention to become pregnant and breastfeeding during the study as confirmed by self-report. Female participants of reproductive potential must be willing to use a medically acceptable method of birth control which include highly effective (e.g. approved hormonal contraceptives, intrauterine device, tubal ligation) or double barrier (e.g. male condom with diaphragm, male condom with cervical cap) methods of contraception or abstinence if that is the usual and preferred lifestyle of the participant
- Presence of cardiac decompensation/heart failure v)
- Diagnosis of any primary psychotic disorder, bipolar disorder, obsessive-compulsive disorder, or post-traumatic stress disorder (current) as confirmed by the MINI
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 |
|---|---|---|
| Intranasal Ketamine (IN)A sterile form of ketamine will be administered intranasally twice weekly for four weeks. Dosing schedule will be determined based on patient's weight using a specialized formula. Patients will be started at the lowest dose during the first treatment session. Dose will be titrated further to therapeutic dose in the following sessions. The dose will be adjusted if patients do not tolerate full therapeutic doses. After receiving the second treatment of each week, participants will be seen by a study physician to determine dosing for the following week. Patients will be monitored by trained personnel for the full duration of the 2 hour supervision period. Vital signs and physical symptoms will be monitored consistently and measurements taken every 30 minutes. Appropriate medications will be provided to manage treatment-related side effects and any adverse events. Labetalol will be used in the management of treatment-related transient hypertension as needed. | Drug | Intranasal Ketamine (IN) |
Primary outcome
Change in symptom severity of depression as measured by the Hamilton Rating Scale for Depression - 24
Time frame: 2 months
Hamilton Rating Scale for Depression (24-item version); This scale is used to quantify the severity of symptoms of depression Scale range: 0-76 (total score) Lower scores indicate lower severity of depressive symptoms (i.e., better outcome) Higher scores indicate higher severity of depressive symptoms (i.e., worse outcome)
7 secondary outcomes
Change in symptom severity of Suicidal Ideation as measured by by the Scale of Suicide Ideation (SSI)
Time frame: 2 months
Safety and tolerability as assessed by changes in Blood Pressure (BP)
Time frame: 1 month
Safety and tolerability as assessed by changes in Heart Rate (BPM)
Time frame: 1 month
Safety and tolerability as assessed by changes in O2 Saturation
Time frame: 1 month
Safety and Tolerability of IN Ketamine as assessed by monitoring of adverse events
Time frame: 2 months
Impact of Ketamine on cortical excitation as measured by intracortical facilitation (ICF)
Time frame: 1 months
Impact of Ketamine on cortical inhibition as measured by short-interval cortical inhibition (SICI)
Time frame: 1 month
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2023.
- Derived from this study: PubMed 34882570Knyahnytska Y, Zomorrodi R, Kaster T, Voineskos D, Trevizol A, Blumberger D. The Safety, Clinical, and Neurophysiological Effects of Intranasal Ketamine in Patients Who Do Not Respond to Electroconvulsive Therapy: Protocol for a Pilot, Open-Label Clinical Trial. JMIR Res Protoc. 2022 Jan 17;11(1):e30163. doi: 10.2196/30163.
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.
Yuliya Knyahnytska, MD, PhD principal investigator
Centre for Addiction and Mental Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intranasal Ketamine (IN) in people with Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
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 7 inclusion and 14 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 Aug 2023. 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 Canada. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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 symptom severity of depression as measured by the Hamilton Rating Scale for Depression - 24 (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05137938, which also lists 1 linked publication.
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 Aug 2023.