A Phase 1 interventional study of Ketamine and Midazolam in Depression, Relapse and Recurrent Depressive Disorder, sponsored by St Patrick's Hospital, Ireland. Terminated at 1 site in Ireland. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2020-01-13.
Sponsored by St Patrick's Hospital, Ireland · Phase 1, Interventional, and Other
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.
8,577 studies on the registry are indexed under Depression; 1,720 are open to participants now.
This study's enrollment of 9 is below the median of 81 across 7,063 interventional studies indexed under Depression.
Browse Depression studies →St Patrick's Hospital, Ireland is the lead sponsor of 7 studies on the registry; none are open to participants now.
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Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
For the randomised pilot trial, RDD patients must have:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
DSM diagnostic criteria
The American Psychiatric Association’s manual of mental health diagnoses. DSM-5 (2013, revised as DSM-5-TR in 2022) replaced DSM-IV, and some studies still name the older edition. “Meets DSM criteria for …” means diagnosed by that edition’s diagnostic criteria, usually by a clinician in an interview.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
MMSE and MoCA
Short tests of memory and thinking, each scored out of 30. Lower scores suggest more difficulty; criteria give a range, either to include people with memory problems or to leave them out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
Drug: Ketamine
Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
Drug: Midazolam
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.
Time frame: 2 years
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.
Time frame: 8 months
Participants were inpatients at St Patrick's Mental Health Services admitted for treatment of an acute depressive episode with a previous history of depression
| Milestone | Ketamine | Midazolam |
|---|---|---|
| Started | 5 | 4 |
| Completed | 3 | 2 |
| Not completed | 2 | 2 |
| Withdrew: Lack of efficacy | 1 | 1 |
| Withdrew: Withdrawal by subject | 1 | 1 |
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.
| Participants | Ketamine | Midazolam |
|---|---|---|
| Completion Rate for Randomised Treatment Phase | 3 | 2 |
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.
| Participants | Ketamine | Midazolam |
|---|---|---|
| Depression Relapse Rate During Treatment and Follow-up Phase | 2 | 3 |
Collected over 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.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Ketamine | 0/5 (0%) | 0/5 (0%) | 1/5 (20%) |
| Midazolam | 0/4 (0%) | 0/4 (0%) | 1/4 (25%) |
| Event | Ketamine | Midazolam |
|---|---|---|
| UrticariaImmune system disorders | 0/5 | 1/4 |
| Delayed hypersensitivity reactionImmune system disorders | 1/5 | 0/4 |
| Age, Categorical(Participants) | Ketamine | Midazolam | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 4 | 4 | 8 |
| >=65 years | 1 | 0 | 1 |
| Sex: Female, Male(Participants) | Ketamine | Midazolam | Total |
|---|---|---|---|
| Female | 2 | 3 | 5 |
| Male | 3 | 1 | 4 |
| Race (NIH/OMB)(Participants) | Ketamine | Midazolam | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 |
| White | 5 | 4 | 9 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Region of Enrollment(participants) | Ketamine | Midazolam | Total |
|---|---|---|---|
| Ireland | 5 | 4 | 9 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — None envisaged: data will be anonymised
The record gives a start of Dec 2015, a primary completion of May 2018 and a completion of May 2018. It does not say whether these dates are actual or estimated.
Results were first posted in Jan 2020, 1 year 7 months after primary completion.
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This study is terminated, as verified in Jan 2020. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Ketamine
St Patrick's Hospital, Ireland