Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression
PHASE4RECRUITING
The goal of this study is to compare the effectiveness of two formulations of ketamine - Spravato® and racemic ketamine - in people with treatment-resistant depression (TRD). The main questions it aims to answer are: * How the two formulations compare in terms of their effectiveness in treating TRD. * How the two formulations compare in their acceptability to patients, safety, effects on patient quality of life and function, and cost effectiveness.
Participants will be randomised to receive either Spravato® or racemic ketamine treatment and asked to complete some questionnaires to assess the effects on mood, treatment acceptability, side effects, quality of life and function, and health economic outcomes.
Study details:
The TREK study is a randomized, prospective, rater blinded (primary outcome raters), parallel group, comparative effectiveness trial of racemic ketamine and Spravato®, comparing their effectiveness, acceptability, safety, effects on quality of life (QOL), function and cost effectiveness after 4 weeks - 6 months of treatment in people with TRD. Participants will be recruited from clinics/hospitals that are providing racemic ketamine and Spravato® treatment services for TRD. Participants will be referred, treated and followed up as per the clinic's normal clinical practice.
Participants who consent to participate in this research study will undergo other processes in addition to the standard treatment procedures provided by their clinic:. * Randomisation to receive racemic ketamine or Spravato®. * Completion of questionnaires to measure treatment effects on mood, acceptability, safety, quality of life and function and cost effectiveness.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
- Adult with treatment-resistant depression (TRD: not responded adequately to at least two different antidepressants of adequate dose and duration) who has a current depressive episode (DSM 5)
- Assessed and attested by clinic psychiatrist as appropriate to receive either racemic ketamine or Spravato® ketamine treatment for TRD
- Aged ≥18 years
- Written informed consent for research study obtained
Exclusion criteria
- Not able to give informed consent
- Any physical or mental condition which, in the opinion of the investigator, could interfere with study participation including outcome assessments
- Patients who require an interpreter/translator for the clinic consent process, due to the infeasibility of obtaining an interpreter for research assessments, including self-rated scales
Eligibility
Age eligible for study : NA
Healthy volunteers accepted : No
Gender eligible for study: ALL
Things to know
Study dates
Study start:
Primary completion:
Study completion finish:
Study type
TREATMENT
Phase
- PHASE4
Study ID
NCT06278779
Intervention or treatment
DRUG: Esketamine group
DRUG: Racemic ketamine
Conditions
- Treatment Resistant Depression
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Research sites nearby
Closest Location:
Royal Prince Alfred Hospital
Select from list below to view details:
Royal Prince Alfred Hospital
Camperdown, New South Wales, Australia
Black Dog Institute
Randwick, New South Wales, Australia
Ramsay Clinic Northside
St Leonards, New South Wales, Australia
Ramsay Clinic Lakeside
Warners Bay, New South Wales, Australia
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Who is running the clinical trial?
TGI
The George Institute
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
| Participant Group/Arm | Intervention/Treatment |
|---|---|
ACTIVE_COMPARATOR: Esketamine group
| Drug: Esketamine group |
ACTIVE_COMPARATOR: Racemic ketamine
| Drug: Racemic ketamine |
What is the study measuring?
Primary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | Change in score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. MADRS includes questions on ten symptoms, each of which yields a score of 0 to 6. The total score ranges from 0 to 60. The higher the MADRS score the more severe the depression. Cutoff points are for levels of depression are: 0 to 6: normal /symptom absent 7 to 19: mild depression 20 to 34: moderate depression 35 to 60: severe depression. | From week 0 to week 4. |
Secondary Outcome
| Measure | Description | Time Frame |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) score | Score on the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is sensitive to change, and is commonly used for treatment trials in depression. See outcome 1 for minimum and maximum values, and whether higher scores indicate a better or worse outcome. | At week 8, month 4 and month 6 |
| Response - Montgomery-Asberg Depression Rating Scale (MADRS) | Response (≥50% improvement in MADRS) | Weeks 4, 8 and months 4 and 6 |
| Remission - Montgomery-Asberg Depression Rating Scale (MADRS) | Remission (MADRS score ≤10) | Weeks 4, 8 and months 4 and 6 |
| DASS-21 | Depression, Anxiety and Stress Scale (DASS-21) - will be used to measure psychological distress. It consists of three 7-item subscales, with items scored on a 4-point Likert scale (0-3) and summed to obtain subscale scores. | Performed weekly from baseline to week 8 inclusive and at 6 month visit. |
| Clinical Global Impression-Improvement (CGI-I) | The Clinical Global Impression - Improvement scale (CGI-I) is used to assess depressive symptom improvement from study baseline. The minimum value is -6 (maximum deterioration) and the maximum value is 6 (ideal improvement). | Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits. |
| Clinical Global Impression-Severity (CGI-S) | The Clinical Global Impression - Severity scale (CGI-S) is used to assess depressive symptom severity. The minimum value is 1 (normal) and the maximum value is 7 (among the most extremely ill patients). | Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits. |
| Columbia Suicide Severity Rating Scale (C-SSRS) | Columbia Suicide Severity Rating Scale (C-SSRS) - short questionnaire that will be used by the clinic teams as a clinical tool to assess suicidality. | Performed weekly from baseline to week 4 inclusive, then at week 8 and at 6 month visits. |
| Speed of response - Clinical Global Impression-Improvement (CGI-I) | Speed of response, assessed by number of treatments required to attain CGI-I score of ≥ 3. | Performed weekly from week 1 to week 4 inclusive, then at week 8 and at 6 month visits. |
| Psychotomimetic symptoms | Assessed via the Ketamine Side Effect Tool (KSET), designed to monitor the acute, cumulative and longer-term safety of ketamine treatment. | Through study completion at each treatment visit, up to 6 months |
| Suicide attempts or gestures | Data collected as an Adverse Event of Special Interest | During 6-month study period |
| Number of Participants with urinary symptoms, as assessed using the Bladder Pain/ Interstitial Cystitis Symptom Score (BPIC-SS) | Bladder Pain-Interstitial Cystitis Symptom Score (BPIC-SS) - a self-report symptom-based instrument that identifies moderate to severe bladder pain syndrome. Side effects of racemic ketamine/Spravato® include inflammation of the bladder endothelium. From 8 questions about bladder/urination pain, patients can score a minimum of 0 (asymptomatic) and a maximum of 38 (severe symptoms). | Performed at baseline, week 4, week 8 and at 6 month visit. |
| Cognitive Failure Questionnaire scores (CFQ) | Cognitive Failures Questionnaire (CFQ) is a self-rated tool to assess subjective impression of cognitive functioning. From 25 questions, patients can score a minimum of 0 (best) and a maximum of 100 (worst). | Performed at baseline, week 4, week 8 and at 6 month visit. |
| Ketamine liking/craving score | Ketamine liking/craving score will be used as a measure of ketamine craving/abuse. A visual analogue scale is used, where patients can score a minimum of 0 (strong dislike/no craving) and a maximum of 30 (very strong liking/constant craving). | Performed at baseline, week 4, week 8 and at 6 month visit. |
| Number of Participants with urinary symptoms, as assessed using the Ketamine Side Effect Tool (KSET) | Assessed via the Ketamine Side Effect Tool (KSET), designed to monitor the acute, cumulative and longer-term safety of ketamine treatment. | Through study completion at each treatment visit, up to 6 months |
| Acceptability Questionnaire | An 8-item self-rated instrument to assess the acceptability of healthcare interventions. This evaluates the constructs of affective attitude, effort burden, ethicality, perceived effectiveness, intervention coherence, self-efficacy, opportunity costs and general acceptability. Patients can score a minimum of 8 (very unacceptable) and a maximum of 40(very acceptable). "If reporting a score on a scale, please include the minimum and maximum values, and whether higher scores mean a better or worse outcome." Appears that not all high scores are positive so makes it hard to address this issue. | Performed at week 4, week 8 and at 6 month visit. |
| End of Treatment questionnaire | Collected via case report form. Captures reason for ceasing, switching or re-starting study medication. | Used at end of the treatment period(s) over the course of the study. |
| Recovering Quality of Life Questionnaire (REQOL-10) | Recovering Quality of Life, 10-item (REQOL-10) is used to assess the quality of life for people with different mental health conditions. Patients can score a minimum of 0 (poorest quality of life) and a maximum of 40 (highest quality of life). | Over 6 month study period |
| WHO Disability Assessment Scale (WHODAS-12) | 12-item WHO Disability Assessment Scale (WHODAS-12) is a 12-item self-rated assessment of health and disability. It will be used to assess functionality. Patients can score a minimum of 0 (no disability) and a maximum of 48 (complete disability). | Over 6 month study period |
| Patient Health Questionnaire-9 (PHQ-9) | Patient Health Questionnaire-9 (PHQ-9) is a self-report screening tool designed to assess the severity of depressive symptoms in individuals and monitors symptom changes and treatment effects over time. Patients can score a minimum of 0 (no depression) and a maximum of 27 (severe depression). | Over 6 month study period |
| Assessment of Quality of Life Questionnaire (AQoL-8D) | Assessment of Quality of Life Questionnaire (AQoL-8D) consists of 35 items covering 8 dimensions: Independent Living, Pain, Senses, Mental Health, Happiness, Coping, Relationships, and Self-worth. It will be used to assess quality of life outcomes and to facilitate the health economics analysis. There is a max patient score of 1 (perfect health) and a minimum score of 0 (deceased) based on weighted utility scores | Over 6 month study period |
| Resource Use Questionnaire (RUQ) | The resource use questionnaire (RUQ) collects information regarding the type and number of contacts with the health system including hospitalisations, consultations and medications. The information is then 'scored' by multiplying indicative unit costs by the number of contacts for each service used. The costs per service are summed to calculate a total health sector cost. The resource use questionnaire also collects information regarding time missed (absenteeism) and time working at reduced capacity (presenteeism) for paid work and time missed from unpaid work. The number of hours missed and working at reduced capacity from paid work will be valued using an average wage rate. The hours missed from unpaid work will be valued using a shadow cost for the value of leisure time. These costs are summed and combined with health sector costs to calculate societal costs. | Over 6 month study period |
| Treatment Preference | The Treatment Preferences questionnaire is a simple 3 item self-report questionnaire which asks participants to indicate their treatment preference for one of the 2 interventions, if any; their strength of preference (slight, moderate or strong); their reason for preference (Prefer this method of receiving the medication; Had this treatment before and benefitted; Past negative experience with the other treatment; Impression from reports, other people or media; Other (please specify)) | Assessed once, prior to randomization |
| Stanford Expectations of Treatment Scale (SETS) | The SETS is a self-report questionnaire that assesses positive and negative treatment expectations with 6 items rated on a 7-point Likert scale from 0 'not agree at all' to 6 'fully agree'; additional questions ask the responder to confirm the treatment they will receive and whether they have received it before as well as whether any specific benefits or harms/negative side effects are expected | Assessed once, after randomization and before first treatment |
| Difficulties in Emotion Regulation Scale-16 (DERS-16) | The DERS-16 is a self-report measure with established internal consistency, reliability and validity that assesses an individual's typical levels of difficulties in emotion regulation. The DERS-16 assesses five aspects of difficulties in emotion regulation: nonacceptance of emotional responses, difficulty engaging in goal-directed behaviour, impulse control difficulties, limited access to emotion regulation strategies, and lack of emotional clarity. | Performed at baseline and week 4 |
| Level of Personality Functioning Scale-Brief Form (LPFS-BF) | The LPFS-BF is a 12-item self-report questionnaire that provides a first impression of impairments in personality functioning. The LPFS-BF consists of 12 items, clustered into two higher order domains: self-functioning and interpersonal functioning. Validity and sensitivity have been established in a range of samples and languages | Performed at baseline and week 4 |
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References
Clinical Trials Gov: Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant DepressionOther trials to consider
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