RESET-TRD; a Randomised trial on oral ESketamine compared to Electroconvulsive Therapy for patients with Treatment Resistant Depressio

Phase 3

Recruiting

• Conditions: sadness; Treatment-resistant depression; 10027946

• Registration Number: NL-OMON56600
• Lead Sponsor: niversitair Medisch Centrum Groningen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 24 June 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 172

Inclusion Criteria

- 18 years or older of age at screening;
- Sufficiënt level of spoken and written Dutch;
- Ability to freely provide written informed consent prior to study
participation;
- Current DSM-5 diagnosis of MDD without psychotic symptoms, ascertained by the
Mini International Neuropsychiatry Interview (MINI-plus);
- At least moderate to severe depression, defined by a MADRS total score >= 20;
- Indication for ECT treatment for the treatment of the current depressive
episode.
- Treatment Resistant Depression, defined as non-response to (or established
non-tolerability of) treatment with at least two different antidepressants plus
an augmentation step such as lithium, mirtazapine or quetiapine during
lifetime, all prescribed in an adequate dose (i.e. defined daily dose) for at
least four weeks;
- Patients agree with initial clinical admission and subsequent
daycare/outpatient treatment.

Exclusion Criteria

• Prior or current bipolar disorder, schizophrenia spectrum, other psychotic
disorders, current MDD with psychotic features (previous MDD with psychotic
features is allowed if the current episode is non-psychotic). All diagnoses
according to DSM-5, assessed with MINI-plus interview at screening;
• The presence of current moderate or severe dependence of alcohol or drugs 6
months within screening according to the DSM-5, not including tobacco-related
and caffeine-related disorders, ascertained by the MINI-plus interview at
screening;
• Current use of a MAOI in excess of a daily dose of 60 mg;
• Recent (within the last four weeks of screening) or current use of cannabis
or any other non-prescribed psychoactive compounds, including Saint John*s
wort, assessed at screening;
• Relevant neurological disorders, such as dementia or epilepsy;
• Recent (within the last four weeks of screening) change of treatment with
antidepressants;
• Planned changes in antidepressant treatment during phase 1 of the study, not
being part of the standard practice of ECT treatment like change in lithium or
anti-epileptics;
• Active suicidal plans, defined by a score higher than 5 (explicit plans for
suicide when there is an opportunity or active preparations for suicide) on the
MADRS*s item for suicidal ideation;
• (Suspected) pregnancy, lactation, or insufficient contraception. In fertile
women, a urine pregnancy test will be performed prior to Phase 1 (screening)
and prior to Phase 2 (month 1) of the study. Current use of benzodiazepine and
benzodiazepine-like agents (zolpidem, zopiclone) in excess of 3 mg lorazepam or
an equivalent per day;
• Recent (within the last four weeks of screening) start or change in the use
of somatic medication that commonly affects mood, like corticosteroids;
• Previous treatment with ECT or esketamine during the current depressive
episode;
• Presence of any absolute contra-indication for esketamine use (according to
the Summaries of Product Characteristics) or ECT (according to Dutch ECT
guidelines, Appendix A), namely pheochromocytoma, increased intracranial
pressure, intracranial surgery (< 6 months), a recent cerebrovascular accident
/ cerebral trauma, glaucoma, recent myocardial infarction (<6 months), unstable
angina pectoris or myocardial disease (New York Heart Association (NYHA) class
IV), aneurysmal vascular disease, severe hypertension, severe hyperthyroidism,
severe liver problems (Child-Pugh class C), severe kidney problems, acute
intermittent porphyria, severe upper airway infection, the use of medication
that esketamine interacts with on a major level, such as xanthine derivates
(aminophylline, theophylline) or previous hypersensitivity to esketamine or its
components;
• Presence of any of the following relative contra-indications for esketamine
use (according to the Summaries of Product Characteristics) or ECT (according
to Dutch ECT guidelines, Appendix A), namely stable angina pectoris,
hypertension, myocardial infarction (> 6 months ago), intracranial process,
unstable cervical spine, carcinoid, severe COPD, severe obesity,
pseudocholinesterase deficiency, malignant hyperthermia and congenital muscle
diseases. Cardiovascular relative contra-indications will lead to consultation
with a colleague from the cardiology department. Thi

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Phase 1<br /><br>The primary objective in phase 1 is to investigate whether oral esketamine<br /><br>treatment is non-inferior to ECT in terms of response rates. The main study<br /><br>parameter comprises the percentage of patients with a treatment response,<br /><br>defined as a >=30% reduction (i.e., MICD) on the MADRS, in the esketamine<br /><br>relative to the ECT condition after eight weeks of treatment.<br /><br><br /><br>Phase 2<br /><br>The primary objective in phase 2 is to compare the efficacy of maintenance<br /><br>treatment with either oral esketamine or ECT in preventing relapse (i.e., loss<br /><br>of response) in patients who responded to the acute treatment (phase 1). The<br /><br>main study parameter comprises the percentage of patients with a depression<br /><br>relapse (i.e., loss of response), defined as a <30% reduction on the MADRS, in<br /><br>the esketamine relative to the ECT condition after 12 months of maintenance<br /><br>treatment.</p><br>