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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-002020-37 | EudraCT Number |
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Inadequate recruitment
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Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam for depression relapse prevention in persons at high risk. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.
Participants will be recruited at admission to St Patrick's University Hospital for treatment of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV)-diagnosed recurrent unipolar depression and followed-up weekly to assess recovery according to standard criteria. Blood samples for epigenetic studies will be taken at baseline. Treatment-as-usual will continue throughout the entire trial. Participants who meet standardised response criteria will then be invited to be randomised to course of four two-weekly ketamine or midazolam (active comparator) infusions. Block randomisation will be independently performed. Physical, psychotomimetic and cognitive outcomes will be monitored before, during and after infusions. Blood samples will be taken at four time-points in the first infusion session and before the final infusion for neuroplasticity biomarker studies.Trial Interventions: participants will receive four two-weekly infusions of either ketamine at 0.05mg/kg or midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Repeated infusions of ketamine 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 200 minutes afterwards.
Participants will be followed up over six months to assess for relapse according to standardised criteria. This is the highest-risk period for relapse and investigators hypothesize that ketamine will provide additional neurotrophic support (assessed by the laboratory biomarker project) which will result in lower relapse rates when compared to midazolam.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ketamine | Experimental | Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. |
|
| Midazolam | Active Comparator | Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Completion Rate for Randomised Treatment Phase | The outcomes for this pilot trial are process outcomes, primarily rates of recruitment and retention. Thus, the completion rate for the randomised treatment phase is the primary outcome. The study is not designed to assess efficacy. | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Depression Relapse Rate During Treatment and Follow-up Phase | Clinical outcomes are secondary in this pilot trial. The 24-item Hamilton Rating Scale for Depression (HRSD-24) was used to assess for the main clinical outcome, the relapse rate over six months. Criteria for relapse are ≥10 point increase in HRSD-24 compared to baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later (if indicated, additional follow-ups will be arranged). Hospital admission, and deliberate self-harm/suicide also constitute relapse. Relapse may also occur during the eight-week treatment phase and is captured here. |
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Inclusion Criteria:
For the randomised pilot trial, RDD patients must have:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Declan McLoughlin | University of Dublin, Trinity College | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St Patrick's University Hospital | Dublin | 8 | Ireland |
None envisaged: data will be anonymised
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Participants were randomised from n=28 participants in an observational phase, all of whom were receiving inpatient treatment for recurrent depressive disorder. Participants were monitored weekly for response to treatment and those who responded were invited to be randomised.
Participants were inpatients at St Patrick's Mental Health Services admitted for treatment of an acute depressive episode with a previous history of depression
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine | Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart. |
| FG001 | Midazolam | Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | Ketamine | Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Completion Rate for Randomised Treatment Phase | The outcomes for this pilot trial are process outcomes, primarily rates of recruitment and retention. Thus, the completion rate for the randomised treatment phase is the primary outcome. The study is not designed to assess efficacy. | All randomised participants who received one infusion were analysed (intention to treat) | Posted | Count of Participants | Participants | 2 years |
|
Adverse event information was collected over the entire study time frame, 29 months, from December 2015 to May 2018. Individual participants were assessed over an approximately seven-month period including their inpatient admission, eight-week randomised treatment phase, and 26-week follow-up period.
Tolerability of the trial agents was assessed at multiple points before, during and after treatment sessions using a battery of assessments used in assessing for physical and psychotomimetic side effects of ketamine (CADSS, BPRS, PRISE and YMRS), standard in the field of ketamine clinical trials for depression, as well as assessment of physical health parameters before, during and after assessments.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ketamine | Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist. Ketamine: A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Delayed hypersensitivity reaction | Immune system disorders | MedDRA (10.0) | Systematic Assessment | Possible delayed hypersensitivity reaction a number of hours following a first ketamne infusion, consisting of rash and hypertension with no airway interference or swelling. Deemed more likely penicillin allergy. Resolved within hours, no treatment. |
Recruitment and randomisation rates in this pilot trial were low, leading to small participant numbers analysed. Due to the potential for breach of confidentiality, limited participant-level information has been reported.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr Martha Finnegan | Trinity College Dublin | 0863638264 | mfinneg@tcd.ie |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Sep 15, 2016 | Dec 18, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D012008 | Recurrence |
| D003866 | Depressive Disorder |
| D003865 | Depressive Disorder, Major |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D008874 | Midazolam |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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A randomised, double-blind, placebo-controlled study designed to assess feasibility of recruitment, randomisation and retention.
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Masking took place by sealed envelope random allocation and double blinding of participants and raters was assessed throughout. The anaesthesiologist administering infusions was aware of the allocation.
| Midazolam | Drug | A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart. |
|
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| 8 months |
| Midazolam |
Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart. |
|
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| Secondary | Depression Relapse Rate During Treatment and Follow-up Phase | Clinical outcomes are secondary in this pilot trial. The 24-item Hamilton Rating Scale for Depression (HRSD-24) was used to assess for the main clinical outcome, the relapse rate over six months. Criteria for relapse are ≥10 point increase in HRSD-24 compared to baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later (if indicated, additional follow-ups will be arranged). Hospital admission, and deliberate self-harm/suicide also constitute relapse. Relapse may also occur during the eight-week treatment phase and is captured here. | Posted | Count of Participants | Participants | 8 months |
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|
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| 0 |
| 5 |
| 0 |
| 5 |
| 1 |
| 5 |
| EG001 | Midazolam | Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist. Midazolam: A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart. | 0 | 4 | 0 | 4 | 1 | 4 |
|
| Urticaria | Immune system disorders | MedDRA (10.0) | Systematic Assessment | Pruritis and urticaria developing two days after the first midazolam infusion, other likely contributors identified (laundry detergent). Resolved with oral antihistamine. |
|
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |