To unravel the neural correlates of the interaction between positive expectation (high/low) and single dose antidepressant treatment (verum/placebo) with esketamine in patients with major depressive disorder MedDRA version: 20.0 Level: SOC Classification code 10037175 Term: Psychiatric disorders System Organ Class: 10037175 - Psychiatric disorders MedDRA version: 21.1 Level: LLT Classification code 10081270 Term: Major depressive disorder System Organ Class: 10037175 - Psychiatric disorders M
Conditions
Interventions
Trade Name: Ketanest S
Product Name: Ketanest S
Pharmaceutical Form: Solution for injection
INN or Proposed INN: Esketamin-Hydrochlorid
CAS Number: 6740-88-1
Concentration unit: mg/ml milligram(s)/mil
Sponsors
Philipps-Universität Marburg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. a current depressive episode lasting at least four weeks 2. an initial score of at least 7 (corresponding to a mild degree of depression) on the Montgomery A°sberg Depression Rating Scale (MADRS) 3. Negative serum pregnancy test in women of childbearing potential. 4. Patients with reproductive potential must agree to maintain highly effective methods of contraception by practicing abstinence or by using at least two methods of birth control from the date of consent through the end of the study. If abstinence could not be practiced, a combination of hormonal contraceptive (oral, injectable, or implants) and a barrier method (condom, diaphragm with a vaginal spermicidal agent) has to be used. 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 176 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. psychotic symptoms (ascertained using SCID-5 Interview measured by module A-E) 2. acute suicidality (clinical assessment by study physician) 3. hypertension > 180/100 mmHg (according to resting blood pressure, as assessed by study physician using blood pressure measurement) 4. hyperthyroidism that has not been sufficiently treated (clinical history by study physician and current thyroid parameters will have to be within the following ranges: TSH 0,34-5,6 mU/l, fT3 3,2-6,9 pmol/l, fT4 7,5-21 pmol/l) 5. severe hepatic impairment (clinical history by study physician and current liver parameters will have to be within the following ranges: serum albumin 3,0mg/dl, prothrombin time 2,3) 6. hypersensitivity to the active substance of esketamine or to any of the excipients listed in section 6.1 of the SmPC (clinical history by study physician) 7. unstable angina or myocardial infarction in the last 6 months (clinical history by study physician) 8. Myocardial failure (clinical history and physical examination by study physician) 9. Glaucoma or perforating eye injuries (clinical history by study physician) 10. patients will be excluded if they have any drug or alcohol dependency/abuse within the previous three months or if they are under acute influence of alcohol (clinical assessment by study physician and alcohol breath test) 11. any contraindications for MRI, i.e. non-removable medical devices (such as pacemakers, insulin pumps, implantable drug infusion pumps etc) or metal devices /foreign bodies (such as aneurysm clips, metal splinters in the eye , intrauterine devices etc) and pregnancy (clinical assessment by study physician and serum pregnancy test) 12. medical conditions likely to affect brain anatomy or physiology (clinical assessment by study physician) 13. age 65 years 14. inability to provide written informed consent 15. Breastfeeding (clinical history by study physician) 16. simultaneous participation in other clinical trials if not permitted by the Principal Investigator 17. Patients for whom an elevated blood pressure or an increased intracranial pressure represents a serious risk will be excluded (clinical history and blood pressure measurement by study physician) 18. Patients with manifest ischemic heart diseases will be excluded (clinical history by study physician) 19. Increased intracranial pressure (clinical history by study physician) 20. Severe psychological disorders other than depression (Structured Clinical Interview for DSM-5 (SCID-5) measured by module A-E) 21. Concomitant therapy with Xanthin-derivates and ergometrin (clinical history by study physician) 22. Treatment with strong inhibitors or inducers of CYP3A4 (for example, but not exclusively, HIV protease inhibitors, Macrolide antibiotics, Azole antifungals, Carbamazepine, Phenobarbital; clinical history by study physician) 23. Diazepam treatment (clinical history by study physician)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Major depressive disorder (MDD) is highly prevalent (8-15%), severely disabling and associated with enormous socioeconomic impact. Antidepressant medication for the treatment of MDD has proven effective in randomized controlled trials (RCTs), however, placebo response is substantial and has been increasing over the last 3 decades. In this double-blind, randomized, controlled parallel-group, 4-arm, monocenter trial project we will employ the factors ‘treatment’ (intravenous esketamine / placebo, single application) and verbally induced ‘expectation’ (high / low) combined with functional magnetic resonance imaging (fMRI, resting state, emotion and reward processing paradigms, on the same day as the esketamine/placebo treatment) to investigate the psychological and neural mechanisms underlying the antidepressant effects of expectation, and how these interact with the pharmacological effects of esketamine.;Secondary Objective: Not appicable See secondery endpoints below;Primary end point(s): Brain activation in networks implicated in (i) reward and (ii) emotion processing, (iii) placebo and (iv) antidepressant treatment response in MDD and (v) the pathophysiology of MDD (in particular the ventromedial prefrontal cortex [VMPFC], rostral anterior cingulate cortex (rACC), amygdala and hippocampus). ;Timepoint(s) of evaluation of this end point: The evaluation will performed during one single day (visit 1) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Behavioural reaction times and hit rates in the Monetary Incentive Delay task. •Changes in depressive symptoms (self-rating beck depression inventory [BDI-II], expert rating Montgomery A°sberg Depression Rating Scale [MADRS]) in response to high vs. low expectation and placebo vs. esketamine. ;Timepoint(s) of evaluation of this end point: The evaluation will performed 4 hours, 2, 3 and 6 days after visit 1 | — |
Countries
Germany
Contacts
Public ContactKKS Marburg
Koordinierungszentrum für Klinische Studien (KKS)
Outcome results
None listed