DepressionPhase 1KINDREDNCT02661061
Ketamine for Relapse Prevention in Recurrent Depressive Disorder
A Phase 1 study testing Ketamine and Midazolam in people with Depression and Relapse, run by St Patrick's Hospital, Ireland at 1 site in Ireland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depression, Relapse, Recurrent Depressive Disorder
- 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
- 9 participants
- Where
- 1 siteIreland
- Study dates
- Dec 2015to 23 May 2018
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 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)
Show all 9Show fewer
- ≥60% decrease from baseline HRSD-24 score and score ≤16
- Standardised Mini-Mental State Examination (sMMSE) score of ≥24
- able to provide informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Ketamine for Relapse Prevention in Recurrent Depressive Disorder: a Randomised, Controlled, Pilot Trial: the KINDRED Trial
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.
Read the detailed description
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.
- Keywords
- ketamine, glutamate, relapse prevention
- Medical subject headings
- Depression, Recurrence, Depressive Disorder, Depressive Disorder, Major
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 four infusions, each two weeks apart.
MidazolamDrug
Also called Hypnovel
A sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Ketamine |
| 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. Receives: Drug: Midazolam |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Secondary outcomes (1)
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.
Measured: 8 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2016 (estimated)
- Study startDec 2015
- Primary completion23 May 2018
- Study completion23 May 2018
Why it stopped: Inadequate recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomised, double-blind, placebo-controlled study designed to assess feasibility of recruitment, randomisation and retention.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 9 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, Principal investigator, University of Dublin, Trinity College
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02661061
- Sponsor's protocol ID
- 20/15
- Other IDs
- 2015-002020-37, 2015
- Acronym
- KINDRED
- Status last verified
- Jan 2020
- First submitted
- 10 Dec 2015
- Last updated
- 13 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: None envisaged: data will be anonymised
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ketamine for Relapse Prevention in Recurrent Depressive Disorder: a Randomised, Controlled, Pilot Trial: the KINDRED Trial
- ClinicalTrials.gov ID
- NCT02661061
- Acronym / sponsor ID
- KINDRED / 20/15
- Keywords
- ketamine, glutamate, relapse prevention
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Inadequate recruitment
- Enrolment
- 9 participants (actual)
- Lead sponsor
- St Patrick's Hospital, IrelandUniversity, hospital or other
- Study start
- Dec 2015
- Primary completion
- 23 May 2018 (actual)
- Study completion
- 23 May 2018 (actual)
- First posted
- 22 Jan 2016 (estimated)
- Results
- Posted 13 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- A randomised, double-blind, placebo-controlled study designed to assess feasibility of recruitment, randomisation and retention.
| Arm | Type | Receives |
|---|---|---|
| Ketamine | Experimental | Drug: KetamineTrial 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 | Drug: MidazolamTrial Interventions: participants will receive four two-weekly infusions of midazolam at 0.045mg/kg. 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 (9 listed)
- ≥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
- received antidepressant treatment for the acute depressive episode(pharmacological, psychotherapeutic or multidisciplinary)
Key exclusion criteria (8 listed)
- Current involuntary admission
- Medical condition rendering unfit for ketamine/midazolam
- Active suicidal intention
- Dementia
- History of Axis 1 diagnosis other than RDD
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 four infusions, each two weeks apart. | Drug | Ketamine |
| MidazolamAlso: HypnovelA sub-anaesthetic dose of midazolam will be administered in four infusions, each two weeks apart. | Drug | Midazolam |
Primary outcome
Completion Rate for Randomised Treatment Phase
Time frame: 2 years
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.
1 secondary outcome
Depression Relapse Rate During Treatment and Follow-up Phase
Time frame: 8 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No. None envisaged: data will be anonymised
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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 principal investigator
University of Dublin, Trinity College
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 and Relapse, 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 9 inclusion and 8 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 13 Jan 2020. 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?
Yes. Results are posted in the registry (first posted 13 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Completion Rate for Randomised Treatment Phase (time frame: 2 years). 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 13 Jan 2020.