INTERVENTION: Pharmaceutical Form: Capsule INN or Proposed INN: Esketamine CAS Number: 33795‐24‐3 Other descriptive name: ESKETAMINE HYDROCHLORIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ INN or Proposed INN: Esketamine CAS Number: 33795‐24‐3 Other descriptive name: ESKETAMINE HYDROCHLORIDE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 30‐ Pharmaceutical form of the placebo: Capsule Route of administration of the placebo: Oral use CONDITION: Therapeutic area: Psychiatry and Psychology [F] ‐ Mental Disorders [F03] Treatment resistant major depressive disorder PRIMARY OUTCOME: Main Objective: The proposed study aims to examine the antidepressant efficacy of oral S‐ketamine augmentation in patients with treatment resistant depression, treated with regular antidepressants in a double‐blind randomised controlled trial. Primary end point(s): The primary objective of this trial is to examine the antidepressant efficacy of oral S‐ketamine augmentation in patients with TRD. This will be measured by the following main study endpoints at the end of treatment: 1) change in symptom severity, expressed as a change in total score on the HDRS17; 2) response, defined as = 50% decrease in total score on the HDRS17; 3) partial response, defined as 25‐49% decrease in total score on the HDRS17. Secondary Objective: Secondary questions involve the effects of oral S‐ketamine on sleep, autobiographical memory, pain, anxiety, anhedonia, suicidal ideation, nicotine dependence, quality of life and consumption of medical care, as well as a detailed assessment of possible side effects caused by the ketamine treatment. Brain activation, brain blood flow and volume parameters, neuroplasticity, glutamate and glutamine concentrations in the brain, biomarkers, and the genotype of the CYP enzyme(s) involved in the metabolism of ketamine will be assessed, to develop a better understanding of the mechanisms of action and metabolism of S‐ketamine. Furthermore, the study will also investigate the duration of effects after discontinuation of S‐ketamine add‐on treatment. Timepoint(s) of evaluation of this end point: At the end of treatment (week 6) SECONDARY OUTCOME: Secondary end point(s): The secondary objectives of this trial will be measured by the following secondary study endpoints: ; ‐ HDRS17 changes in total sum score after the discontinuation of treatment; ; ‐ IDS‐SR changes in total sum score during and after the discontinuation of treatment;; ‐ HDRS17 changes and IDS‐SR changes in symptom dimension scores during and after the discontinuation of treatment; ; ‐ BSS changes in total sum score during and after the discontinuation of treatment; ; ‐ SHAPS changes in total sum score during and after the discontinuation of treatment;; ‐ fMRI reward task changes in total sum score during treatment; ; ‐ CGI severity changes and CGI improvement scores during and after the discontinuation of treatment;; ‐ BAI changes in total sum score during and after the discontinuation of treatment;; ‐ GCPS changes in item scores during and after the discontinuation of treatment;; ‐ FTND changes in total sum score during and after the discontinuation of treatment;; ‐ AMT changes in total specific sum score during and after the discontinuation of treatment;; ‐ EQ‐5D‐5L changes in total sum score calculated using the Dutch tariff and in VAS score, during and after the discontinuation of treatment;; ‐ Changes of brain activation in the prefrontal cortex, limbic structures, insula and default mode network during treatment; ; ‐ Changes of the prefrontal cortex and limbic structures volumes during treatment; ; ‐ Changes of glutamate and glutamine concentrations in the anterior cingulate cortex of the brain during treatment; ; ‐ Changes of blood flow in the brain during treatment; ; ‐ Changes of biomarker patterns in blood and urine during and after the discontinuation of treatment; ; ‐ Changes in gene expression patterns, measured by the use of RNA, during and after the discontinuation of treatment; ; ‐ SAFTEE changes in total sum score and item scores during and after the discontinuation of treatment; ; ‐ ISDI changes in symptom dimension scores during and after the discontinuation of treatment;; ‐ QPE changes in total sum score and symptom dimensions scores during and after the discontinuation of treatment;; ‐ DSS changes in total sum score during and after the discontinuation of treatment;; ‐ Body weight changes during and after the discontinuation of treatment;; ‐ Blood pressure changes during and after the discontinuation of treatment;; ‐ Liver enzyme level changes during treatment; ; ‐ Incremental costs per additional percentage point of patients recovered from depression, with recovery assessed by the means of the HDRS17, and defined as a more than 50% decrease in score from week 1 to week 6 and 10;; ‐ Incremental costs per QALY gained, with QALYs assessed by means of the EQ‐5D‐5L and calculated over the 10 week study period; ; ‐ Expected changes in the flows of expenditure in the Dutch health care system after the adoption of ketamine as a new intervention for treatment resistant depression; ; ‐ Report on new pharmacokinetics knowledge of S‐ketamine and norketamine after oral administration;; ‐ Report on associations between S‐ketamine and norketamine pharmacokinetics and changes on the HDRS17; ; ‐ Report on new genotype knowledge of the CYP enzyme(s) involved in the metabolism of S‐ketamine. ; Timepoint(s) of evaluation of this end point: There will be different timepoints for the secondary end points: ; ‐ During treatment (week 0 ‐ week 6);; ‐ At the end of treatment (week 6);; ‐ At follow‐up (week 7, 8 and 10); INCLUSION CRITERIA: In order to be eligible to participate in this study, a subject must meet all the following criteria: ‐ Male or female, age range: 18 to 80 years; ‐ Signed informed consent; ‐ Good understanding of spoken and written Dutch; ‐ DSM‐5 diagnosis of MDD, first or recurrent episode, ascertained by the Mini International Neuropsychiatry Interview (MINI‐plus); ‐ TRD, defined as nonresponse to at least 3 different classes of antidepressants during lifetime, all given in an adequate dose (i.e. defined daily dose) for at least 4 weeks; ‐ At least moderately severe depression, defined by a score higher than 18 on HDRS17; ‐ Current treatment with an officially approved antidepressant medicine. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 118 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Epistemonikos ID: 616454307f47bb0043700598310d143cca5c969c
First added on: Aug 24, 2024
