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Major Depressive EpisodePhase 1KARMA-depNCT03256162

Ketamine as an Adjunctive Therapy for Major Depression

A Phase 1 study testing Ketamine and Midazolam in people with Major Depressive Episode and Unipolar Depression, run by St Patrick's Hospital, Ireland at 1 site in Ireland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an adjunctive therapy for depression. 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
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
25 participants
Where
1 siteIreland
Study dates
7 Sep 2017to 21 Sep 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 version (HRSD-24) score of ≥21
  • Voluntary admission for treatment of an acute depressive episode
  • Meet Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition (DSM-V) criteria for a major depressive disorder (MDD) and bipolar affective disorder (current episode depression)

Who cannot join

  • Current involuntary admission
  • Medical condition rendering unfit for ketamine/midazolam
  • Active suicidal intention
  • Dementia
  • History of Axis 1 diagnosis other than major depression
  • Electroconvulsive Therapy (ECT) administered within the last two months
Show all 9Show fewer
  • Alcohol/substance dependence in previous six-months
  • Pregnancy or inability to confirm use of adequate contraception during the trial
  • Breastfeeding women

Trial locations and contacts

1 site in 1 country.

Ireland1 site

  • St Patrick's University Hospital

    Dublin, D8

Other trials in Ireland

About this study

Official title: Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial

Randomised, controlled, parallel-group, pilot clinical trial of ketamine vs. midazolam as an adjunctive therapy for depression. The main purpose of the pilot study is to assess trial processes to help inform a future definitive trial.

Read the detailed description

Pragmatic, randomised, controlled, parallel-group, pilot trial. Trial participants will be patients admitted to St Patrick's University Hospital for treatment of a depressive episode. The investigators aim to recruit up to 20 participants who will be eligible for this study and randomly allocate 10 patients to each group. The participants will undergo usual inpatient care as prescribed by their treating team for the index acute depressive episode. Both participants and assessors will be blind to treatment allocation. Consented participants will be randomly allocated in a 1:1 ratio to a four week course of either once-weekly ketamine or midazolam 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. Both groups will continue treatment as usual. Participates will also be followed up over a three month period.

Being tested
Ketamine, Midazolam
Keywords
ketamine, glutamate
Medical subject headings
Depressive Disorder, Bipolar Disorder

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 one week apart.

  • MidazolamDrug

    Also called Hypnovel

    A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.

Study groups in NCT03256162
Study groupRoleWhat they receive
KetamineExperimentalParticipants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
Receives: Drug: Ketamine
MidazolamActive comparatorParticipants will receive four once-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.

  1. The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24)

    The HRSD assesses severity of depressive symptoms and is commonly used to measure depression severity. It was initially a 17-item format with the optional addition of 4 items making up the 21-item version. In addition to the original 21 items, the 24-item HRSD includes items on helplessness, hopelessness and worthlessness; its score range is 0-77, with higher scores reflecting greater burden of depressive symptoms.

    Response to antidepressant treatment is defined as achieving ≥60% decrease from baseline HRSD-24 and score ≤16. Remission criteria are ≥60% decrease in HRSD from baseline and score ≤10. Criteria for relapse are ≥10 point increase in HRSD-24 compared to responder baseline score plus HRSD ≥16; in addition, increase in the HRSD should be maintained one week later.

    Participants will have a baseline (T0) HRSD-24 score. This will be repeated 1 week after each of 4 once-weekly infusions (T1-4) and follow-up measures after another 5 (T9) and 11 (T15) weeks, week 15 is reported.

    Measured: 15 weeks

Secondary outcomes (6)

  1. 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.

    Participants will have a baseline (T0) QIDS-SR16 score. This will be repeated one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks. Week 15 scores are reported.

    Measured: 15 weeks

  2. 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 of the four once-weekly infusions.

    Measured: 4 weeks

  3. 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 of the four once-weekly infusions.

    Measured: 4 weeks

  4. 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 of the four once-weekly infusions.

    Measured: 4 weeks

  5. 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 of the side effects in the following symptom domains; Gastrointestinal, Heart, Skin, Nervous System, Eyes/Ears, Genital/Urinary, Sleep, Sexual Functioning, and Other. Each domain has multiple symptoms which can be endorsed. For each domain the patient rates whether or not the symptoms are tolerable or distressing. Data below represent the number of participants from which there was an endorsement of each listed event.

    Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.

    Measured: 4 weeks

  6. 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 infusions 1 and 4 and 12 weeks after the final infusion.

    Measured: 15 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Aug 2017
  2. Study start7 Sep 2017
  3. Primary completion21 Sep 2018
  4. Study completion21 Sep 2018

Resources

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
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03256162
Sponsor's protocol ID
01/17
Other IDs
2016-004764-18, 2016
Acronym
KARMA-dep
Status last verified
Jan 2020
First submitted
2 Aug 2017
Last updated
18 Jan 2020
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Vekhova KA, Namiot ED, Jonsson J, Schioth HB. Ketamine and Esketamine in Clinical Trials: FDA-Approved and Emerging Indications, Trial Trends With Putative Mechanistic Explanations. Clin Pharmacol Ther. 2025 Feb;117(2):374-386. doi: 10.1002/cpt.3478. Epub 2024 Oct 20.

    PubMed 39428602

  • Gallagher B, Foley M, Slattery CM, Gusciute G, Shanahan E, McLoughlin DM. Ketamine as an adjunctive therapy for major depression - a randomised controlled pragmatic pilot trial (Karma-Dep Trial). HRB Open Res. 2022 Jan 27;3:90. doi: 10.12688/hrbopenres.13182.2. eCollection 2020.

    PubMed 35036831

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ketamine and Midazolam in people with Major Depressive Episode and Unipolar 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 4 inclusion and 9 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: finished, as of the sponsor's last update on 18 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 18 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?

The Hamilton Rating Scale for Depression-24 Item Version (HRSD-24) (time frame: 15 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03256162, which also lists 2 linked publications.

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 18 Jan 2020.

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