DepressionPhase 1NCT04082858
Ketamine Interleaved With Electroconvulsive Therapy for Depression
A Phase 1 study testing Ketamine and Midazolam in people with Depression, run by St Patrick's Hospital, Ireland at 1 site in Ireland.
Trial summary
Pragmatic, randomised, controlled, parallel group, pilot clinical trial of ketamine vs. midazolam interleaved with electroconvulsive therapy (ECT) as an adjunctive treatment for a major depressive episode. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression
- What is being tested?
- Ketamine and Midazolam
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteIreland
- Study dates
- 6 Jan 2020to 3 Jun 2020
- Phase
- Phase 1
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 years old
- Able to provide informed consent
- Voluntary admission for treatment of an acute depressive episode
- Meet DSM-V criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)
- Montgomery Asberg Depression Rating Scale 10 item version (MADRS) score of ≥20
- Referred for treatment with ECT
- Sufficiently physically healthy to receive ketamine/midazolam and ECT
Who cannot join
- Inability to provide informed consent
- Current involuntary admission
- History of Axis 1 diagnosis other than major depression
- Medical condition rendering unfit for ECT
- Active suicidal intention
- Presence of major neurological or organic brain disorder
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- Alcohol/substance dependence in previous six-months
- Pregnancy or inability to confirm use of adequate contraception during the trial
- Breastfeeding women
- Contraindications to ketamine
- Contraindications to midazolam
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ketamine Interleaved With Electroconvulsive Therapy for Depression, A Pragmatic Randomised Controlled Pilot Trial
Pragmatic, randomised, controlled, parallel group, pilot clinical trial of ketamine vs. midazolam interleaved with electroconvulsive therapy (ECT) as an adjunctive treatment for a major depressive episode. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
Read the detailed description
Patients referred for treatment with ECT at St Patrick's Mental Health Services for treatment of a depressive episode will be eligible for recruitment to the clinical trial. Participants will be invited to be randomised to a course of twice-weekly ketamine or midazolam infusions for the duration of ECT. Participants will receive the first allocated infusion following the first or second treatment with ECT. Block randomisation will be independently performed. Infusions will be delivered on separate days to ECT. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions.Treatment-as-usual will continue throughout the entire trial.
Trial Interventions: participants will receive twice-weekly infusions of either ketamine at 0.5mg/Kg or midazolam at 0.045mg/Kg. All infusions will be administered by a Consultant Anaesthetist. Repeated infusions of allocated drug have been shown to be safe and well tolerated by patients with mental illness. Minor haemodynamic changes and psychotomimetic side effects can occur and will be assessed regularly during infusions and for 120 minutes afterwards. Participants will be followed-up at six weeks and three months after the final infusion to assess for relapse according to standardised criteria.
- Conditions
- Depression
- Keywords
- Ketamine, Electroconvulsive Therapy, Depression, ECT
- 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 Ketalar
A sub-anaesthetic dose of ketamine will be administered in twice-weekly infusions
MidazolamDrug
Also called Hyponovel
A sub-anaesthetic dose of midazolam will be administered in twice-weekly infusions
| Study group | Role | What they receive |
|---|---|---|
| Ketamine | Experimental | Participants will receive twice-weekly infusions of ketamine at 0.05mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist. Receives: Drug: Ketamine |
| Midazolam | Active comparator | Participants will receive twice-weekly infusions of midazolam at 0.045mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist. Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery Asberg Depression Rating Scale (MADRS)
A validated, 10-item, depression rating scale to measure depressive symptomatology and response to treatment. During the infusion sessions MADRS scores will be obtained immediately pre-infusion and at +60 and +120 minutes afterwards. Depression measures will be repeated at week 6 and at three-months post infusion. This outcome measure assesses the change in MADRS scores during the pilot trial.
A course of ECT can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks.
Measured: 18 weeks
Secondary outcomes (6)
The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR16)
The QIDS-SR16 is a validated self-report measure of depressive symptoms. This consists of 16 questions rated 0-3. Its score range is 0-48, with higher scores reflecting greater burden of depressive symptoms.
During the infusion sessions in the pilot trial QIDS scores will be obtained immediately pre-infusion and at +60 and +120 minutes afterwards. For longer-term follow-up, depression measures will be repeated at weeks 6 and three-month follow-up.
A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks (12 weeks + 6 weeks).
Measured: 18 weeks
The Clinician-Administered Dissociative States Scale (CADSS)
The CADSS measures dissociative symptoms. It will be administered before, during and after infusions in order to capture the range of possible subjective side effects of either agent. This consists of 23 questions and scores for each question range from 0-4. The maximum score is 92 with higher scores indicating more dissociative symptoms.
Participants will have the CADSS performed before, during (+30mins) and after (+60mins) each infusions.
A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks.
Measured: 6 weeks
The Brief Psychiatric Rating Scale (BPRS)
The BPRS measures psychotomimetic effects. The investigators will use the positive symptoms subscale of the Brief Psychiatric Rating Scale. The 4-item positive symptoms subscale measures suspiciousness, hallucinations, unusual thought content, and conceptual disorganisation. Each question is scored between 0-7. The maximum score in this 4-item questionnaire is 28. Higher scores indicate more severe psychotic symptoms.
Participants will have the BPRS performed before, during (+30mins) and after (+60mins) each infusion.
A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks
Measured: 6 weeks
Young Mania Rating Scale (YMRS; mood item)
Investigators will use the mood item of them YMRS to assess for psychotomimetic effects. This item is rated 0-4. The higher scores reflect elevated mood.
Participants will have the YMRS performed before, during (+30mins) and after (+60mins) each infusion.
A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks
Measured: 6 weeks
The Patient-Rated Inventory of Side Effects (PRISE)
The PRISE will be used to document other general adverse events by patients before, during and after infusions. This is a patient self-report used to qualify side effects by identifying and evaluating the tolerability of each symptom. It is a 9 item assessment.
Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each infusion.
A course of ECT can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. The above measures will be repeated for the duration of the trial i.e. for up to 6 weeks
Measured: 6 weeks
The Montreal Cognitive Assessment (MoCA)
The MOCA was designed as a rapid screening instrument for mild cognitive dysfunction. It assesses different cognitive domains: attention and concentration, executive functions, memory, language, conceptual thinking, calculations, and orientation. It is scored out of a maximum of 30. The higher scores indicate better cognition.
The MOCA will be performed at baseline, one day after the first and final infusions and at 12 weeks after the final infusion.
A course of Electroconvulsive Therapy (ECT) can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks (12 weeks + 6 weeks).
Measured: 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Sep 2019
- Study start6 Jan 2020
- Primary completion3 Jun 2020
- Study completion3 Jun 2020
Why it stopped: Inadequate recruitment due to COVID-19
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Pragmatic, randomised, controlled, parallel group, pilot clinical trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- St Patrick's Hospital, Ireland
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof Declan McLoughlin, St Patrick's Hospital, Ireland
- Investigators
- Declan McLoughlin, PhD, Principal investigator, St Patrick's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04082858
- Sponsor's protocol ID
- 11/18
- Status last verified
- Sep 2021
- First submitted
- 19 Aug 2019
- Last updated
- 9 Sep 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Sep 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine Interleaved With Electroconvulsive Therapy for Depression, A Pragmatic Randomised Controlled Pilot Trial
- ClinicalTrials.gov ID
- NCT04082858
- Acronym / sponsor ID
- 11/18
- Conditions
- Depression
- Keywords
- Ketamine, Electroconvulsive Therapy, Depression, ECT
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate recruitment due to COVID-19
- Enrolment
- 3 participants (actual)
- Lead sponsor
- St Patrick's Hospital, IrelandUniversity, hospital or other
- Study start
- 6 Jan 2020 (actual)
- Primary completion
- 3 Jun 2020 (actual)
- Study completion
- 3 Jun 2020 (actual)
- First posted
- 9 Sep 2019 (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.
Pragmatic, randomised, controlled, parallel group, pilot clinical trial of ketamine vs. midazolam interleaved with electroconvulsive therapy (ECT) as an adjunctive treatment for a major depressive episode. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
Detailed description
Patients referred for treatment with ECT at St Patrick's Mental Health Services for treatment of a depressive episode will be eligible for recruitment to the clinical trial. Participants will be invited to be randomised to a course of twice-weekly ketamine or midazolam infusions for the duration of ECT. Participants will receive the first allocated infusion following the first or second treatment with ECT. Block randomisation will be independently performed. Infusions will be delivered on separate days to ECT. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions.Treatment-as-usual will continue throughout the entire trial.
Trial Interventions: participants will receive twice-weekly infusions of either ketamine at 0.5mg/Kg or midazolam at 0.045mg/Kg. All infusions will be administered by a Consultant Anaesthetist. Repeated infusions of allocated drug have been shown to be safe and well tolerated by patients with mental illness. Minor haemodynamic changes and psychotomimetic side effects can occur and will be assessed regularly during infusions and for 120 minutes afterwards. Participants will be followed-up at six weeks and three months after the final infusion to assess for relapse according to standardised criteria.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Pragmatic, randomised, controlled, parallel group, pilot clinical trial
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineParticipants will receive twice-weekly infusions of ketamine at 0.05mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist. |
| Midazolam | Active comparator | Drug: MidazolamParticipants will receive twice-weekly infusions of midazolam at 0.045mg/kg for the duration of treatment with ECT. All infusions will be administered by a Consultant Anaesthetist. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- ≥18 years old
- Able to provide informed consent
- Voluntary admission for treatment of an acute depressive episode
- Meet DSM-V criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)
- Montgomery Asberg Depression Rating Scale 10 item version (MADRS) score of ≥20
Key exclusion criteria (11 listed)
- Inability to provide informed consent
- Current involuntary admission
- History of Axis 1 diagnosis other than major depression
- Medical condition rendering unfit for ECT
- Active suicidal intention
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: KetalarA sub-anaesthetic dose of ketamine will be administered in twice-weekly infusions | Drug | Ketamine |
| MidazolamAlso: HyponovelA sub-anaesthetic dose of midazolam will be administered in twice-weekly infusions | Drug | Midazolam |
Primary outcome
Montgomery Asberg Depression Rating Scale (MADRS)
Time frame: 18 weeks
A validated, 10-item, depression rating scale to measure depressive symptomatology and response to treatment. During the infusion sessions MADRS scores will be obtained immediately pre-infusion and at +60 and +120 minutes afterwards. Depression measures will be repeated at week 6 and at three-months post infusion. This outcome measure assesses the change in MADRS scores during the pilot trial. A course of ECT can be prescribed for a maximum to 6 weeks (12 sessions in total, twice weekly for 6 weeks). Trial infusions will be administered twice weekly on separate days to ECT, for the duration of treatment with ECT. Therefore, trial infusions may be administered for up to 6 weeks. Participants will be followed up for three months (12 weeks) after their final infusion. In total, participants outcome measures will be repeated for up to 18 weeks.
6 secondary outcomes
The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR16)
Time frame: 18 weeks
The Clinician-Administered Dissociative States Scale (CADSS)
Time frame: 6 weeks
The Brief Psychiatric Rating Scale (BPRS)
Time frame: 6 weeks
Young Mania Rating Scale (YMRS; mood item)
Time frame: 6 weeks
The Patient-Rated Inventory of Side Effects (PRISE)
Time frame: 6 weeks
The Montreal Cognitive Assessment (MoCA)
Time frame: 18 weeks
Results and safety
The study was stopped early (reason given: Inadequate recruitment due to COVID-19). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Sep 2021.
- 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.
Declan McLoughlin, PhD principal investigator
St Patrick's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketamine and Midazolam in people with Depression, run by St Patrick's Hospital, Ireland at 1 site in Ireland.
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 11 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 9 Sep 2021. 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 Ireland. 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.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Inadequate recruitment due to COVID-19). Results are not available in the source record.
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?
Montgomery Asberg Depression Rating Scale (MADRS) (time frame: 18 weeks). 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 9 Sep 2021.