Effects of Mineralocorticoid Receptor Stimulation on Cognitive Bias and Social Cognition in Patients With Major Depression and Healthy Controls: What's the Role of NMDA Receptors?

Mineralocorticoid Receptor, NMDA Receptor and Cognitive Function in Depression

Sponsors

Lead sponsor: Charite University, Berlin, Germany

Collaborator: NeuroCure Clinical Research Center, Charite, Berlin

Source Charite University, Berlin, Germany
Brief Summary

The steroid hormone cortisol is released in response to stress and acts in the central nervous system upon glucocorticoid (GR) and mineralocorticoid receptors (MR). GR are widely distributed across the brain while MR are predominantly expressed in the hippocampus and prefrontal cortex - two brain areas closely related to memory and executive function. Stimulation of MR leads to an increase of glutamate that act on glutamatergic NMDA receptors in the hippocampus and prefrontal cortex. In previous studies, the investigators have shown that fludrocortisone, a mineralocorticoid receptor (MR) agonist, improves memory and executive function in depressed patients and healthy controls. However, depressed patients not only exhibit cognitive deficits in traditional neuropsychological domains such as memory or executive function. In addition, there are depression-specific alterations such as cognitive bias and deficits in social cognition, two clinically highly relevant areas. Therefore, the specific aims of this renewal proposal are two-fold:

- To examine whether beneficial effects of fludrocortisone in depressed patients can be extended to depression-specific cognitive bias and to social cognition

- To determine whether beneficial effects of fludrocortisone depend on NMDA-receptor function and whether these beneficial effects can be enhanced by NMDA receptor stimulation.

The investigators hypothesize that fludrocortisone will improve cognitive bias and social cognition in depressed patients and that its beneficial effects depend on the NMDA receptor. Therefore, the investigators further hypothesize that the effects of fludrocortisone can be enhanced by co-administration of the partial NMDA receptor agonist D-cycloserine.

The study not only advances current knowledge by further examining the mechanism of action by which MR stimulation exerts beneficial effects on cognition but extends these effects to depression-specific cognitive bias and alterations in social cognition. Furthermore, a potential interaction between MR and NMDA receptors is highly clinically relevant given the promising results with NMDA receptor antagonists in the treatment of major depression.

Overall Status Completed
Start Date September 27, 2016
Completion Date February 11, 2019
Primary Completion Date February 11, 2019
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
Emotional dot probe 1 hour
Secondary Outcome
Measure Time Frame
Facial recognition task 1 hour
Multifaceted Empathy Test (MET) 1 hour
Virtual Water Maze 1 hour
Enrollment 232
Condition
Intervention

Intervention type: Drug

Intervention name: Placebo

Description: Placebo

Intervention type: Drug

Intervention name: Fludrocortisone

Description: Fludrocortisone

Intervention type: Drug

Intervention name: D-Cycloserine

Description: D-Cycloserine

Eligibility

Criteria:

Inclusion Criteria:

- Age 18-65 years

- Depressed male and female patients according to DSM-V & minimum of 17-items Hamilton Depression Score of 18

- healthy controls

- informed consent signed

Exclusion Criteria:

- Current use of antidepressants, antipsychotics, or mood stabilizer

- Relevant medical or neurological disorders

- Pregnancy or unsure contraception

- Relevant psychiatric comorbidity (bipolar or psychotic disorders)

- Active alcohol or other substance abuse/dependance

Gender: All

Minimum age: 18 Years

Maximum age: 65 Years

Healthy volunteers: Accepts Healthy Volunteers

Overall Official
Last Name Role Affiliation
Christian Otte, MD Principal Investigator Charité University Medical Center Berlin, Dept. of Psychiatry
Location
facility Charité Universitätsmedizin Berlin
Location Countries

Germany

Verification Date

June 2020

Responsible Party

Responsible party type: Principal Investigator

Investigator affiliation: Charite University, Berlin, Germany

Investigator full name: Prof. Dr. Christian Otte

Investigator title: Professor of Psychiatry

Has Expanded Access No
Condition Browse
Number Of Arms 4
Arm Group

Arm group label: Placebo+Placebo

Arm group type: Placebo Comparator

Description: Placebo: pill, 8mm, single dose, Lichtenstein, Winthrop Arzneimittel GmbH.

Arm group label: Fludrocortisone+Placebo

Arm group type: Active Comparator

Description: Fludrocortisone: pill, Astonin H 0,1gm, single dose, Merck Serono GmbH Placebo: pill, 8mm, single dose, Lichtenstein, Winthrop Arzneimittel GmbH.

Arm group label: Placebo+D-Cycloserine

Arm group type: Active Comparator

Description: Placebo: pill, 8mm, single dose, Lichtenstein, Winthrop Arzneimittel GmbH. D-Cycloserine: capsule, Cycloserine 250mg, single dose, King Pharmaceuticals Ltd

Arm group label: Fludrocortison+D-Cycloserine

Arm group type: Active Comparator

Description: Fludrocortisone: pill, Astonin H 0,1gm, single dose, Merck Serono GmbH D-Cycloserine: capsule, Cycloserine 250mg, single dose, King Pharmaceuticals Ltd

Acronym MISO
Patient Data No
Study Design Info

Allocation: Randomized

Intervention model: Parallel Assignment

Intervention model description: randomized double-blind placebo-controlled parallel group design

Primary purpose: Basic Science

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Source: ClinicalTrials.gov