Enoxolone in Major Depression - Biomarker-outcome Relationship

NCT05570110 | Recruiting Phase 1

• 1 other identifier: MNS_02.1
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

Many different forms of depression exist. It is difficult to predict to what treatment a given patient with depression responds. Studies demonstrate that biomarkers can help to distinguish different forms of depression. Simple markers, like aldosterone/cortisol in body fluids, blood pressure and inflammation markers , have been identified as predictors of therapy resistance in depression. Enoxolone is a molecule derived from the licorice plant and has demonstrated an effect on these biomarkers, which may imply an improved response. The current randomized placebo controlled study is assessing whether the presence of markers of therapy resistance can predict a preferential effect of enoxolone vs. placebo on clinical outcome. Secondarily, it is tested whether these markers change differentially in the treatment groups. Finally, the relationship between the change of the markers and clinical change will be assessed.

Conditions

Unipolar Depression

Keywords

Atypical depression;

Outcome Measures

Primary Outcomes (4)

• Plasma and urine aldosterone/cortisol ratio

  ratio of plasma aldosterone/cortisol at awakening; ratio of nocturnal urine aldosterone concentration/urine cortisol concentration

  Baseline, as predictor for differentiation of treatment groups clinical response

• C-reactive protein

  C-reactive protein in plasma

  Baseline, as predictor for differentiation of treatment groups clinical response and change from baseline (4 weeks)

• Systolic blood pressure

  Systolic blood pressure at rest at baseline as a predictor for treatment differentiation

  Baseline, as predictor for differentiation of treatment groups clinical response

• Depression rating

  Hamilton depression rating scale (HAMD) - 17 items; higher is worse

  change from baseline to week 4, with systolic blood pressure as covariate

Secondary Outcomes (8)

• Urine aldosterone/cortisol ratio

  change from baseline to week 4

• Plasma ratio of sodium/potassium

  change from baseline to week 4

• Nocturnal heart rate variability

  change from baseline to week 4

• Nocturnal blood pressure dip (difference between pre-sleep and minimal nocturnal blood pressure

  change from baseline to week 4

• Depression self rating

  change from baseline to week 4

Other Outcomes (4)

• Lateral cerebral ventricular volume

  change from baseline to 4 weeks

• Corpus callosum volume

  change from baseline to 4 weeks

• Choroid Plexus Volume

  change from baseline to 4 weeks

Study Arms (2)

enoxolone

EXPERIMENTAL

100 mg enoxolone in a capsule

Drug: Enoxolone

placebo

PLACEBO COMPARATOR

Placebo in a capsule

Drug: Enoxolone

Interventions

Enoxolone DRUG

one capsule of active or placebo in the evening

Also known as: glycyrrhetinic acid

enoxolone; placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unipolar Depression
• in women: Contraceptive means

You may not qualify if:

• Schizophrenic and delusional disorders
• Neurological diseases in which central nervous system involvement is known, such as epilepsies, storage diseases; severe mental retardation
• Internistic diseases of moderate or higher severity, which may make participation in the study risky from a clinical point of view. In particular, multiple systolic blood pressure (measured after at least 5 min supine position) of \> 145 mm Hg as well as hypokalemia (\< 3.5 mmol/l) and clinically relevant ECG changes
• Poorly controlled diabetes mellitus (HbA1c \> 10)
• Pregnancy or active desire for pregnancy for the duration of the study
• Non-consent or inability to consent to the study
• Treatment with the following substances: spironolactone or eplerenone; systemic glucocorticoids
• Treatment with ketamine or electroconvulsive therapy in the last 3 months before randomization
• Acute suicidality
• Intolerance to licorice preparations or licorice contents.

Sponsors & Collaborators

• Philipps University Marburg: lead
• Slovak Academy of Sciences: collaborator

Study Sites (1)

Clinic for Psychiatry and Psychotherapy

Marburg, Hesse, 35039, Germany

RECRUITING

Related Publications (5)

• Murck H. Discovery of Personalized Treatment for Immuno-Metabolic Depression-Focus on 11beta Hydroxysteroid Dehydrogenase Type 2 (11betaHSD2) and Toll-like Receptor 4 (TLR4) Inhibition with Enoxolone. Pharmaceuticals (Basel). 2025 Oct 10;18(10):1517. doi: 10.3390/ph18101517.

  PMID: 41155634 BACKGROUND

• Murck H, Luerweg B, Hahn J, Braunisch M, Jezova D, Zavorotnyy M, Konrad C, Jansen A, Kircher T. Ventricular volume, white matter alterations and outcome of major depression and their relationship to endocrine parameters - A pilot study. World J Biol Psychiatry. 2021 Feb;22(2):104-118. doi: 10.1080/15622975.2020.1757754. Epub 2020 May 15.

  PMID: 32306867 BACKGROUND

• Murck H, Lehr L, Hahn J, Braunisch MC, Jezova D, Zavorotnyy M. Adjunct Therapy With Glycyrrhiza Glabra Rapidly Improves Outcome in Depression-A Pilot Study to Support 11-Beta-Hydroxysteroid Dehydrogenase Type 2 Inhibition as a New Target. Front Psychiatry. 2020 Dec 10;11:605949. doi: 10.3389/fpsyt.2020.605949. eCollection 2020.

  PMID: 33362613 BACKGROUND

• Engelmann J, Murck H, Wagner S, Zillich L, Streit F, Herzog DP, Braus DF, Tadic A, Lieb K, Muller MB. Routinely accessible parameters of mineralocorticoid receptor function, depression subtypes and response prediction: a post-hoc analysis from the early medication change trial in major depressive disorder. World J Biol Psychiatry. 2022 Oct;23(8):631-642. doi: 10.1080/15622975.2021.2020334. Epub 2022 Jan 25.

  PMID: 34985381 BACKGROUND

• Murck H, Braunisch MC, Konrad C, Jezova D, Kircher T. Markers of mineralocorticoid receptor function: changes over time and relationship to response in patients with major depression. Int Clin Psychopharmacol. 2019 Jan;34(1):18-26. doi: 10.1097/YIC.0000000000000239.

  PMID: 30300165 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder

Interventions

Glycyrrhetinic Acid

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pentacyclic Triterpenes; Triterpenes; Terpenes; Hydrocarbons; Organic Chemicals

Study Officials

• Harald Murck, MD PhD

  Philipps University Marburg

  STUDY DIRECTOR

Central Study Contacts

Ulrich Schu, MD

CONTACT

+49 6421 5865200; schu@uni-marburg.de

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Active and Placebo Capsules of the same shape and size are utilized
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Apl. Professor

Model Details: Randomized parallel group design, first two subjects open label.

Study Record Dates

• First Submitted: September 28, 2022
• First Posted: October 6, 2022
• Study Start: September 23, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: December 8, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: available after study completion
• Access Criteria: CDA or other agreements

Locations

DE (1)