NCT03062150: MISO

Mineralocorticoid Receptor, NMDA Receptor and Cognitive Function in Depression

Completed NA Last updated 23 June 2020

What this trial tests

NA trial testing Placebo in Major Depression in 232 participants. Completed in 11 February 2019.

Timeline

27 September 2016

Primary endpoint
11 February 2019

11 February 2019

Quick facts

Lead sponsor	Charite University, Berlin, Germany
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	quadruple
Primary purpose	basic science
Enrollment	232
Start date	27 September 2016
Primary completion	11 February 2019
Estimated completion	11 February 2019
Sites	1 location across Germany

Drugs / interventions tested

• Placebo
• Fludrocortisone (fludrocortisone) — full drug profile →
• D-Cycloserine — full drug profile →

Conditions studied

• Major Depression — all drugs for Major Depression →

Sponsor

Charite University, Berlin, Germany

Who can join

Adults 18 to 65, any sex, with Major Depression. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cognitive and emotional empathy after stimulation of brain mineralocorticoid and NMDA receptors in patients with major depression and healthy controls.
   Nowacki J, Wingenfeld K, Kaczmarczyk M, Chae WR, et al · · 2020 · cited 14× · PMID 32722659 · DOI 10.1038/s41386-020-0777-x
2. Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.
   Loeffler DA. · · 2024 · cited 2× · PMID 38872626 · DOI 10.3389/fnagi.2024.1368200