Dehydroepiandrosterone (DHEA) as augmentation of standard antidepressants in treatment-resistant depression: a randomized controlled trial (DARE-Trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2025-11-04

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

German Research Foundation (Deutsche Forschungsgemeinschaft - DFG)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Therapy, Safety

To determine whether add-on 100 mg/d DHEA to continued standard antidepressant medication improves depression to a greater extent than add-on placebo in subjects with treatment-resistant depression

Secondary objectives 1

1. To determine whether add-on 100 mg/d DHEA to continued standard antidepressant medication improves response rates, remission rates, patients’ impression of change, clinician’s impression of severity and change, quality of life, social functioning and self-report depression severity to a greater extent than adjunct placebo in subjects with treatment-resistant depression. Furthermore, changes in glucose, glycosylated hemoglobin (HbA1c), total, HDL- and LDL-cholesterol, C-reactive protein (CRP), and interleukin-6 levels from baseline to week 6 will be determined.

Conditions and MedDRA coding

Treatment Resistant Depression (TRD)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Patient provided written informed consent
2. The patient is capable of giving consent (has sufficient knowledge of German and clearly understands the nature, significance and scope, including risks, of the medical procedure)
3. The patients is aged between 18 and 75 years (≥ 18 and ≤ 75)
4. The patient has an episode of major depression according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edition)
5. The patient has treatment-resistant depression (TRD), defined as non-response to at least one 4-week antidepressant treatment trial (including the current treatment) in the index episode (corresponding to level 1 resistance to treatment failure according to the Maudsley staging method)
6. The patient has a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 20
7. The patient is receiving antidepressant medication (SSRI or SNRI or tricyclic antidepressant or mirtazapine or bupropion) for at least 4 weeks, the dosage is at least at the approved minimum therapeutic dosage and has been unchanged for at least 14 days prior to screening visit.
8. The patient had less than three (<3) treatment attempts with antidepressants in the current MDE (current treatment attempts not included).

Exclusion criteria 32

1. The patient has current clinically significant suicidal ideation with intent, corresponding to a score of 4 or 5 for ideation on the C-SSRS, or a suicidal attempt within the past 6 months, as indicated by the C-SSRS at screening visit
2. The patient has or has had sex hormone-dependent cancer (e.g. breast cancer, ovarian cancer, endometrial cancer, prostate cancer)
3. The patient is allergic or has contraindication to DHEA or lactulose and cellulose
4. The patient has previous diagnosis of chronic kidney disease stage G3b (or higher) or GFR < 30 ml/min.
5. The Patient is taking antidepressants other than those listed as inclusion criterion (SSRI, SNRI, tricyclic antidepressants, bupropion, mirtazapine)
6. The patient is taking psychotropic medication, e.g. antipsychotics, anticonvulsants, lithium or Johannis herbs. Allowed substances include benzodiazepines, non-benzodiazepines (Zopiclon, Zolpidem or Eszopiclon) and antidepressants listed under inclusion criteria.
7. The patient is using non-selective, irreversible MAO inhibitors (e.g. tranylcypromine) or selective, reversible MAO-A inhibitors (e.g. moclobemide) or the reversible non-selective MAO inhibitor linezolid
8. The patient has insulin-dependent diabetes mellitus
9. The patient has an untreated and unstable general medical condition (e.g. hypertension with end organ damage or hypertensive derailment)
10. The patient is pregnant or breastfeeding.
11. The patient of childbearing age shows an unwillingness to use an effective contraceptive method (defined as a Pearl Index < 1)
12. The patient fulfills the criteria for psychotic depression according to DSM-5
13. The patient currently has or has a history of venous thromboembolism (VTE) (deep vein thrombosis, pulmonary embolism)
14. The patient currently has or has a history of arterial thromboembolic disease (e.g. angina pectoris, myocardial infarction, stroke)
15. The patient has a thrombophilic disease (e.g. protein C, protein S or antithrombin deficiency)
16. The patient has porphyria
17. The patient has clinically significant untreated hypothyroidism
18. The patient has clinically significant abnormalities in the 12-lead ECG (e.g. prolongation of the QTc interval ≥ 500 ms) as performed during screening visit
19. The patient is a vulnerable person (defined as: persons deprived their liberty, confined to an institution by court or administrative order, persons that may have Insufficient power, intelligence, education, resources, strength, or other needed attributes to protect their own interests, or unable to explicitly give consent)
20. The patient might be dependent on representative of the sponsor, the investigator or the trial site
21. The patient is currently participating in another interventional clinical trial.
22. The patient's laboratory values show clinically significant abnormalities
23. The patient meets the criteria for schizophrenia, schizoaffective disorder or bipolar disorder in M.I.N.I according to DSM-5
24. The patient currently has liver disease with liver-specific levels outside the age- and gender-specific reference intervals [elevations of GOT or GPT above 3 times the upper normal value (ULN)]
25. The patient meets the criteria for a dependency disorder in the M.I.N.I. for DSM-5
26. The patient has dementia or moderate to severe cognitive impairment.
27. The Patient is currently taking DHEA or has taken it within the last 14 days prior to screening visit.
28. The patients is currently taking hormone replacement therapy with sex hormones (other than contraceptives)
29. The patient has undiagnosed genital bleeding
30. The patient has untreated endometrial hyperplasia
31. The patient has diagnosis of prostatic hyperplasia.
32. The patient has a medical history of liver failure and/or bilirubin above 3 times the normal range and reduced total protein.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change score from baseline to week 6 in Montgomery-Asberg-Depression Rating Scale (MADRS)

Secondary endpoints 4

1. Response, defined as 50% MADRS score reduction from baseline; Remission, defined as MADRS score <10
2. Changes in BDI-II from baseline to week 6, CGI-S, CGI-I, PGIC, and SOFAS will be determined, and EuroQol-5 with MCID as well as ASEX will also be collected
3. Change in glucose, glycosylated hemoglobin (HbA1c), total, HDL- and LDL-cholesterol, C-reactive protein (CRP), and interleukin-6 levels from baseline to week 6
4. Safety endpoints of AE, tolerability and acceptability

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Hindenburgdamm 30, Lichterfelde Lichterfelde

City

Berlin

Postcode

12203

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Christian Otte

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Carolin Lehn

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications