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.
Ketamine for Relapse Prevention in Recurrent Depressive Disorder
Brief Summary
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.
Intervention / Treatment
A randomised, double-blind, placebo-controlled study designed to assess feasibility of recruitment, randomisation and retention.
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Ketamine (DRUG)A sub-anaesthetic dose of ketamine will be administered in four infusions, each two weeks apart.
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Midazolam (DRUG)A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart.
Condition or Disease
- Depression
- Relapse
- Recurrent Depressive Disorder
- Major Depressive Disorder
Phase
Study Design
| Study type: | INTERVENTIONAL |
|---|---|
| Status: | Terminated |
| Study results: | No Results Available |
| Age: | 18 Years and older (Adult, Older Adult) |
| Enrollment: | 9 (ACTUAL) |
| Funded by: | Other |
| Allocation: | Randomized |
| Primary Purpose: | Other |
MaskingMasking 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. QUADRUPLE:
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Clinical Trial Dates
| Start date: | Dec 01, 2015 | |
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| Primary Completion: | May 23, 2018 | ACTUAL |
| Completion Date: | May 23, 2018 | ACTUAL |
| Study First Posted: | Jan 22, 2016 | ESTIMATED |
| Results First Posted: | Jan 13, 2020 | ACTUAL |
| Last Updated: | Jan 07, 2020 |
Sponsors / Collaborators
Lead Sponsor:
St Patrick's Hospital, Ireland
Responsible Party:
N/A
Location
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.
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.
Participant Groups
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Trial Interventions: participants will receive four two-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
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Trial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
Eligibility Criteria
| Sex: | All |
|---|---|
| Minimum Age: | 18 |
| Age Groups: | Adult / Older Adult |
| Healthy Volunteers: | Yes |
Inclusion Criteria:
* ≥18 years old
* Hamilton Rating Scale for Depression, 24-item (HRSD-24) score of ≥21
* Voluntary admission for treatment of acute depressive episode
* Meet DSM-IV criteria for recurrent depressive disorder (RDD): ≥2 previous depressive episodes with at least 2-months(consecutive) subthreshold or no symptoms in between PLUS(to enrich the sample for those at high risk for relapse) must also have experienced ≥3 major depressive episodes(including index episode) within the previous 2 years
For the randomised pilot trial, RDD patients must have:
* received antidepressant treatment for the acute depressive episode(pharmacological, psychotherapeutic or multidisciplinary)
* ≥60% decrease from baseline HRSD-24 score and score ≤16
* Standardised Mini-Mental State Examination (sMMSE) score of ≥24
* able to provide informed consent
Exclusion Criteria:
* Current involuntary admission
* Medical condition rendering unfit for ketamine/midazolam
* Active suicidal intention
* Dementia
* History of Axis 1 diagnosis other than RDD
* Electroconvulsive therapy (ECT) for treatment of current depressive episode
* Alcohol/substance abuse in previous six months
* Pregnancy or inability to confirm use of adequate contraception during the trial
* ≥18 years old
* Hamilton Rating Scale for Depression, 24-item (HRSD-24) score of ≥21
* Voluntary admission for treatment of acute depressive episode
* Meet DSM-IV criteria for recurrent depressive disorder (RDD): ≥2 previous depressive episodes with at least 2-months(consecutive) subthreshold or no symptoms in between PLUS(to enrich the sample for those at high risk for relapse) must also have experienced ≥3 major depressive episodes(including index episode) within the previous 2 years
For the randomised pilot trial, RDD patients must have:
* received antidepressant treatment for the acute depressive episode(pharmacological, psychotherapeutic or multidisciplinary)
* ≥60% decrease from baseline HRSD-24 score and score ≤16
* Standardised Mini-Mental State Examination (sMMSE) score of ≥24
* able to provide informed consent
Exclusion Criteria:
* Current involuntary admission
* Medical condition rendering unfit for ketamine/midazolam
* Active suicidal intention
* Dementia
* History of Axis 1 diagnosis other than RDD
* Electroconvulsive therapy (ECT) for treatment of current depressive episode
* Alcohol/substance abuse in previous six months
* Pregnancy or inability to confirm use of adequate contraception during the trial
Primary Outcomes
Secondary Outcomes
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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.
More Details
| NCT Number: | NCT02661061 |
|---|---|
| Acronym: | KINDRED |
| Other IDs: | 20/15 |
| Study URL: | https://clinicaltrials.gov/study/NCT02661061 |
Last updated: Sep 29, 2023