Ketamine Clinical Trials
Orale ketamine als aanvullende behandeling bij patiënten met een therapieresistente depressie
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Organisation Name: UMCG
Overal Status: Planned
Start Date: 2016-10-01
Lead Sponsor: UMCG
Brief Summary: Rationale: Major depressive disorder (MDD) is a common mental disorder with an impressive disease burden, for which currently available treatments (medication, psychotherapy and electroconvulsive therapy - ECT) unfortunately may be in-effective. Around 30% of patients have therapy-resistant depression (TRD), defined as having no or only a partial response to a range of treatments. These patients often spend years in chronic depression, and there is a strong need to develop additional options to relieve this suffering.
A novel intervention that has shown rapid antidepressant effects is intravenous (IV) ketamine infusion. Ketamine currently is a well-known anaesthetic. Intravenous ketamine however has strong psychomimetic effects and is often given only once, leading to rapid relapse of depression. Oral ketamine administration is less invasive, may be provided for longer periods of time and current evidence shows a more benign side effect profile. Despite these potential benefits, the efficacy and tolerability of oral ketamine for TRD have not been sufficiently investigated.
Objective: The proposed study aims to examine the antidepressant efficacy of oral S-ketamine augmentation in patients with TRD treated with regular antidepressants in a double-blind randomised controlled trial. 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.
Study design: A randomised controlled add-on trial with two arms of treatment, oral S-ketamine vs. placebo, administered for 6 weeks under double-blind conditions. Clinical interviews and self-report questionnaires are performed before treatment, repeatedly during treatment, shortly before the end of treatment and at follow-up. Neuroimaging is performed before and at the end of treatment. Collection of blood and urine takes place before and during treatment and at follow-up. During the trial, all participants continue the antidepressant medication they had before study start.
Study population: Subjects are 128 inpatients and outpatients diagnosed with at least a moderately severe MDD (Hamilton Depression Rating Scale 17 items (HDRS17) - score higher than 18), aged between 18 and 80 years, and not having responded to at least 3 different antidepressant medications.
Intervention: One group of participants receives oral S-ketamine 3 times per day with a tapered start and finish. The other group of participants receives placebo. Participants in both groups will continue their ongoing antidepressant medication.
Main study parameters/endpoints: The primary outcomes are: 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
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