Ketamine as an Adjunctive Therapy for Major Depression (KARMA-dep)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03256162|
Recruitment Status : Completed
First Posted : August 21, 2017
Last Update Posted : November 27, 2018
|Condition or disease||Intervention/treatment||Phase|
|Major Depressive Episode Unipolar Depression Bipolar Depression||Drug: Ketamine Drug: Midazolam||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||25 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Ketamine as an Adjunctive Therapy for Major Depression - a Randomised Controlled Pilot Trial: The KARMA-Dep Trial|
|Actual Study Start Date :||September 7, 2017|
|Actual Primary Completion Date :||September 21, 2018|
|Actual Study Completion Date :||September 21, 2018|
Participants will receive four once-weekly infusions of ketamine at 0.05mg/kg. All infusions will be administered by a consultant anaesthetist.
A sub-anaesthetic dose of ketamine will be administered in four infusions, each one week apart.
Other Name: Ketalar
Active Comparator: Midazolam
Participants will receive four once-weekly infusions of midazolam at 0.045mg/kg. All infusions will be administered by a consultant anaesthetist.
A sub-anaesthetic dose of midazolam will be administered in four infusions, each one week apart.
Other Name: Hypnovel
- The Hamilton Rating Scale for Depression-24 item version (HRSD-24) [ Time Frame: 15 weeks ]
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 one week after each of four once-weekly infusions (T1-4) and follow-up measures after another five (T9) and 11 (T15) weeks.
- The Quick Inventory of Depressive Symptoms, self-report version (QIDS-SR16) [ Time Frame: 15 weeks ]
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.
- The Clinician-Administered Dissociative States Scale (CADSS) [ Time Frame: 4 weeks ]
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.
- The Brief Psychiatric Rating Scale (BPRS) [ Time Frame: 4 weeks ]
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.
- Young Mania Rating Scale (YMRS; mood item) [ Time Frame: 4 weeks ]
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.
- The Patient-Rated Inventory of Side Effects (PRISE) [ Time Frame: 4 weeks ]
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.
Participants will have the PRISE performed before, during (+30mins) and after (+60mins) each of the four once-weekly infusions.
- The Montreal Cognitive Assessment (MoCA) [ Time Frame: 15 weeks ]
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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03256162
|St Patrick's University Hospital|
|Dublin, Ireland, D8|
|Principal Investigator:||Declan M McLoughlin, PhD||St Patrick's Mental Health Services and Trinity College Dublin|