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Major DepressionMISONCT03062150

Mineralocorticoid Receptor, NMDA Receptor and Cognitive Function in Depression

A study testing Fludrocortisone and D-Cycloserine in people with Major Depression, run by Charite University, Berlin, Germany at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for
Major Depression
What is being tested?
Fludrocortisone and D-Cycloserine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
232 participants
Where
1 siteGermany
Study dates
27 Sep 2016to 11 Feb 2019
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • Healthy volunteers accepted
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Charité Universitätsmedizin Berlin

    Berlin, 12203

Other trials in Germany

About this study

Official title: 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?

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.
Read more

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.

Being tested
Placebo, Fludrocortisone, D-Cycloserine
Medical subject headings
Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PlaceboDrug

    Placebo

  • FludrocortisoneDrug

    Fludrocortisone

  • D-CycloserineDrug

    D-Cycloserine

Study groups in NCT03062150
Study groupRoleWhat they receive
Placebo+PlaceboPlacebo comparatorPlacebo: pill, 8mm, single dose, Lichtenstein, Winthrop Arzneimittel GmbH.
Receives: Drug: Placebo
Fludrocortisone+PlaceboActive comparatorFludrocortisone: pill, Astonin H 0,1gm, single dose, Merck Serono GmbH Placebo: pill, 8mm, single dose, Lichtenstein, Winthrop Arzneimittel GmbH.
Receives: Drug: Placebo; Drug: Fludrocortisone
Placebo+D-CycloserineActive comparatorPlacebo: pill, 8mm, single dose, Lichtenstein, Winthrop Arzneimittel GmbH. D-Cycloserine: capsule, Cycloserine 250mg, single dose, King Pharmaceuticals Ltd
Receives: Drug: Placebo; Drug: D-Cycloserine
Fludrocortison+D-CycloserineActive comparatorFludrocortisone: pill, Astonin H 0,1gm, single dose, Merck Serono GmbH D-Cycloserine: capsule, Cycloserine 250mg, single dose, King Pharmaceuticals Ltd
Receives: Drug: Fludrocortisone; Drug: D-Cycloserine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Emotional dot probe

    In this task, two stimuli (each a photography of a face) are presented quickly on a computer screen (500 ms), and one face stimulus is replaced by a probe (1100 ms). Face pictures can show a sad, happy or neutral expression and are paired as neutralneutral, neutral-sad, or neutral-happy. Participants respond as fast as possible by pressing a key to correspond to the location of the probe.

    Attentional bias can be derived by the average reaction time when the probe replaces negative stimuli (sad faces), the average reaction time when the probe replaces neutral stimuli (neutral faces), and the average reaction time of positive (happy faces) and neutral stimuli (neutral faces).

    Measured: 1 hour

Secondary outcomes (3)

  1. Facial recognition task

    This emotion recognition task features two basic emotions - sadness and anger - and a number of control trials containing neutral face expressions. Overall, 6 male and 6 female faces were taken from the NIMSTIM scale (Tottenham et al. (2009); http://www.macbrain.org/resources.htm).

    Two graduations from the full emotion (100%) were created (40% and 80%) and are presented in 24 trials per percentile rank in shades of grey. In addition, 24 control Trials are presented with 0% (neutral) emotion. Overall, the task contains 120 trials in randomized order. Each face is shown for 1 second and is replaced by a grey screen, which requests an answer by showing the three possible answers (sadness, anger, neutral). This screen is presented for 4 seconds and participants make their Responses by pressing one of three keys on the keyboard (arrow keys). Reaction time and correct responses are measured.

    Measured: 1 hour

  2. Multifaceted Empathy Test (MET)

    To assess cognitive and emotional empathy, the MET will be used (Dziobek et al , 2008) in a modified version (Hurlemann et al , 2007; Dziobek et al , 2011; Ritter et al , 2011). The MET is a PC-assisted test consisting of photographs that show 30 picture Stimuli with people in emotionally charged situations. To assess cognitive empathy, participants will be required to infer the mental state of the subject in the photo and will be asked to indicate the correct one from a list of four. To assess emotional empathy, participants will be asked to rate the degree of empathic concern they feel for the person in the Picture (Likert scale, 1 = not at all, 9 = very much).

    Measured: 1 hour

  3. Virtual Water Maze

    Participants are placed in a virtual reality, presented on a computer screen, consisting of a room with a pool in the center. In the pool, there is an invisible platform, that participants have to reach as fast as possible. Participants can move in an ego-perspective with a joystick. In several trials, participants learn to reach the platform. The better participants learn, the faster they reach the platform and the shorter is the path they used.

    In the last trial, participants do not get to know whether they reached the platform. The time (sec) spent in the right quadrant, is the outcome measurement, used to determine visuospatial memory.

    Measured: 1 hour

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2017
  2. Study start27 Sep 2016
  3. Primary completion11 Feb 2019
  4. Study completion11 Feb 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Randomised
Intervention model
Parallel groups
Model description
randomized double-blind placebo-controlled parallel group design
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
232 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03062150
Sponsor's protocol ID
OT 209/7-1
Other IDs
2014-005239-15, 2014
Acronym
MISO
Status last verified
Jun 2020
First submitted
15 Feb 2017
Last updated
23 Jun 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Otte C, Wingenfeld K, Kuehl LK, Kaczmarczyk M, Richter S, Quante A, Regen F, Bajbouj M, Zimmermann-Viehoff F, Wiedemann K, Hinkelmann K. Mineralocorticoid receptor stimulation improves cognitive function and decreases cortisol secretion in depressed patients and healthy individuals. Neuropsychopharmacology. 2015 Jan;40(2):386-93. doi: 10.1038/npp.2014.181. Epub 2014 Jul 18.

    PubMed 25035081

  • Hinkelmann K, Wingenfeld K, Kuehl LK, Fleischer J, Heuser I, Wiedemann K, Otte C. Stimulation of the mineralocorticoid receptor improves memory in young and elderly healthy individuals. Neurobiol Aging. 2015 Feb;36(2):919-24. doi: 10.1016/j.neurobiolaging.2014.09.008. Epub 2014 Sep 16.

    PubMed 25442112

  • Otte C, Wingenfeld K, Kuehl LK, Richter S, Regen F, Piber D, Hinkelmann K. Cognitive function in older adults with major depression: Effects of mineralocorticoid receptor stimulation. J Psychiatr Res. 2015 Oct;69:120-5. doi: 10.1016/j.jpsychires.2015.08.001. Epub 2015 Aug 4.

    PubMed 26343603

  • Nowacki J, Wingenfeld K, Kaczmarczyk M, Chae WR, Abu-Tir I, Deuter CE, Piber D, Hellmann-Regen J, Otte C. Cognitive and emotional empathy after stimulation of brain mineralocorticoid and NMDA receptors in patients with major depression and healthy controls. Neuropsychopharmacology. 2020 Dec;45(13):2155-2161. doi: 10.1038/s41386-020-0777-x. Epub 2020 Jul 28.

    PubMed 32722659

Questions about this trial

What is this clinical trial studying?

A study testing Fludrocortisone and D-Cycloserine in people with Major Depression, run by Charite University, Berlin, Germany at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Emotional dot probe (time frame: 1 hour). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03062150, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2020.

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