Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-resistant Depression

Treatment Resistant Depression Clinical Trial

— TREK  

Official title:

Comparative Effectiveness Study of Two Forms of Ketamine for Treatment-Resistant Depression: a Randomised, Rater-blinded Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06278779
• Other study ID #: X23-0311
• Status: Recruiting
• Phase: Phase 4
• Start date: June 3, 2024
• Est. completion date: April 2027

Study information

• Verified date: June 2024
• Source: The George Institute
• Contact: Simone Jacoby
• Phone: 80524300
• Email: sjacoby[@]georgeinstitute.org.au
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 162
• Est. completion date: April 2027
• Est. primary completion date: April 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Treatment Resistant Depression

Intervention

Drug:
• Esketamine group
The recommended dosing for Spravato is: Weeks 1-4: Starting Day 1 dose: < 65 years: 56 mg = 65 years: 28 mg Subsequent doses: 28 mg (= 65 years), 56 mg or 84 mg twice weekly Weeks 5-8: 28 mg (= 65 years), 56 mg or 84 mg once weekly From Week 9: 28 mg (= 65 years), 56 mg or 84 mg every 2 weeks or once weekly
• Racemic ketamine
Typically, dosing will begin at the standard dose of 0.5 mg/kg and adjusted as needed using an ascending dose titration schedule: 0.5 mg/kg 0.6 mg/kg 0.75 mg/kg 0.9 mg/kg Further increments by 0.1-0.2 mg/kg, up to max 1.5 mg/kg

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Ramsay Clinic Albert Road	Melbourne	Victoria
Australia	Black Dog Institute	Randwick	New South Wales
Australia	Gold Coast University Hospital	Southport	Queensland
Australia	Ramsay Clinic Northside	St Leonards	New South Wales
Australia	Ramsay Clinic Lakeside	Warners Bay	New South Wales

Sponsors (2)

Lead Sponsor	Collaborator
The George Institute	The University of New South Wales

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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 and month 6
Secondary	Response - Montgomery-Asberg Depression Rating Scale (MADRS)	Response (=50% improvement in MADRS)	Weeks 4, 8 and month 6
Secondary	Remission - Montgomery-Asberg Depression Rating Scale (MADRS)	Remission (MADRS score =10)	Weeks 4, 8 and month 6
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	Suicide attempts or gestures	Data collected as an Adverse Event of Special Interest	During 6-month study period
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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.
Secondary	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.
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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