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Treatment Resistant Depression (TRD)Phase 3DARENCT07843927

Dehydroepiandrosterone (DHEA) as Augmentation of Standard Antidepressants in Treatment-resistant Depression.

A Phase 3 study testing Dehydroepiandrosterone (DHEA) in people with Treatment Resistant Depression (TRD), run by Charite University, Berlin, Germany at 9 sites in Germany.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Major depressive disorder (MDD) is a major contributor to impaired health worldwide. Initial antidepressant treatment of MDD does not lead to response in up to 50 % of patients. TRD (Treatment Resistant Depression) is associated with increased rates of recurrence, mortality as well as increased treating costs compared… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Treatment Resistant Depression (TRD)
What is being tested?
Dehydroepiandrosterone (DHEA)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
320 participants
Where
9 sitesGermany
Study dates
22 Jun 2026to 30 Sep 2028
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient provided written informed consent
  • -,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)
  • The patients is aged between 18 and 75 years (≥ 18 and ≤ 75)
  • The patient has an episode of major depression according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edi-tion)
  • 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 (correspond-ing to level 1 resistance to treatment failure according to the Maudsley staging method)
  • The patient has a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 20
  • 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 thera-peutic dosage and has been unchanged for at least 14 days prior to screening visit.
  • The patient had less than three (<3) treatment attempts with anti-depressants in the current MDE (current treatment attempts not in-cluded).

Who cannot join

  • 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
  • The patient fulfills the criteria for psychotic depression according to DSM-5
  • The patient meets the criteria for schizophrenia, schizoaffective disorder or bipolar disorder in M.I.N.I according to DSM-5
  • The patient meets the criteria for a dependency disorder in the M.I.N.I. for DSM-5
  • The patient has dementia or moderate to severe cognitive impair-ment. Exclusion Criteria Related to IMP
  • The Patient is currently taking DHEA or has taken it within the last 14 days prior to screening visit.
Show all 31Show fewer
  • The patients is currently taking hormone replacement therapy with sex hormones (other than contraceptives)
  • The patient has undiagnosed genital bleeding
  • The patient has untreated endometrial hyperplasia The patient has or has had sex hormone-dependent cancer (e.g. breast cancer, ovarian cancer, endometrial cancer, prostate can-cer)
  • The patient is allergic or has contraindication to DHEA or lactulose and cellulose
  • The patient has previous diagnosis of chronic kidney disease stage G3b (or higher) or GFR < 30 ml/min.
  • The patient has diagnosis of prostatic hyperplasia. Exclusion Criteria Related to standard antidepressant medication (AxMP)
  • The Patient is taking antidepressants other than those listed as in-clusion criterion (SSRI, SNRI, tricyclic antidepressants, bupropion, mirtazapine)
  • The patient is taking psychotropic medication, e.g. antipsychotics, anticonvulsants, lithium or Johannis herbs. Allowed substances in-clude benzodiazepines, non-benzodiazepines (Zopiclon, Zolpidem or Eszopiclon) and antidepressants listed under inclusion criteria.
  • 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 line-zolid
  • The patient has insulin-dependent diabetes mellitus General Safety Exclusion Criteria
  • The patient has an untreated and unstable general medical condi-tion (e.g. hypertension with end organ damage or hypertensive de-railment)
  • The patient has a medical history of liver failure and/or bilirubin above 3 times the normal range and reduced total protein
  • The patient is pregnant or breastfeeding.
  • The patient of childbearing age shows an unwillingness to use an effective contraceptive method (defined as a Pearl Index < 1)
  • The patient currently has or has a history of venous thromboembo-lism (VTE) (deep vein thrombosis, pulmonary embolism)
  • The patient currently has or has a history of arterial thromboem-bolic disease (e.g. angina pectoris, myocardial infarction, stroke)
  • The patient has a thrombophilic disease (e.g. protein C, protein S or antithrombin deficiency)
  • The patient has porphyria
  • The patient has clinically significant untreated hypothyroidism
  • 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
  • The patient is a vulnerable person (defined as: persons deprived their liberty, confined to an institution by court or administrative or-der, persons that may have Insufficient power, intelligence, educa-tion, resources, strength, or other needed attributes to protect their own interests, or unable to explicitly give consent)
  • The patient might be dependent on representative of the sponsor, the investigator or the trial site The patient is currently participating in another interventional clini-cal trial.
  • Laboratory Exclusion Criteria
  • The patient's laboratory values show clinically significant abnor-malities
  • The patient currently has liver disease with liver-specific levels out-side the age- and gender-specific reference intervals [elevations of GOT or GPT above 3 times the upper normal value (ULN)]

Trial locations and contacts

9 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Christian Otte, MD contact

0049 30 450 617615

christian.otte@charite.de

Deniz Yildirim Dogan, MD contact

Deniz-Yildirim.Dogan@charite.de

9 sites in 1 country

Germany9 sites, 9 recruiting

  • Klinik für Psychiatrie, Psychotherapie und Psychosomatik der Universität Augsburg

    Augsburg

    Alkomiet Hasan, MD

    Recruiting

  • Charité - Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie

    Berlin, State of Berlin, 12203

    Recruiting

  • Alexianer St. Hedwig Krankenhaus, Berlin

    Berlin, 10115

    Nicola Schoofs, MD

    Recruiting

  • Universitätsklinikum Frankfurt, Klinik für Psychiatrie, Psychosomatik und Psychotherapie,

    Frankfurt

    Andreas Reif, MD

    Recruiting

  • Klinik für Psychiatrie und Psychotherapie am Universitätsklinikum Freiburg

    Freiburg im Breisgau

    Katharina Domschke, MD

    Recruiting

  • Universitätsklinikum Hamburg-Eppendorf, Klinik und Poliklinik für Psychiatrie und Psychotherapie

    Hamburg

    Gregor Leicht, MD

    Recruiting

  • Universitätsklinikum Leipzig, Klinik und Poliklinik für Psychiatrie und Psychotherapie

    Leipzig

    Maria Strauß, MD

    Recruiting

  • Klinik für Psychiatrie und Psychotherapie am LMU Klinikum

    München

    Conelius Schüle, MD

    Recruiting

  • Helios Hanseklinikum Stralsund Klinik und Poliklinik für Psychiatrie

    Stralsund

    Deborah Janowitz

    Recruiting

Other trials in Germany

About this study

Official title: Dehydroepiandrosterone (DHEA) as Augmentation of Standard An-tidepressants in Treatment-resistant Depression: a Randomized Controlled Trial (DARE-Trial) - A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With Group Sequential Design

Major depressive disorder (MDD) is a major contributor to impaired health worldwide. Initial antidepressant treatment of MDD does not lead to response in up to 50 % of patients. TRD (Treatment Resistant Depression) is associated with increased rates of recurrence, mortality as well as increased treating costs compared to MDD. Treatment op-tions for TRD remain limited with lithium, quetiapine and esketamine being the only recommended and approved augmentation strategies in the EU. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, is a promising, safe and tolerable adjunctive treatment op-tion. DHEA has been meta-analytically shown to elicit antidepressant effects and to be safe both in MDD and for depressive symptoms in other medical diseases. However, previous RCTs (Randomized con-trolled trial) were small and no study has yet tested the antidepressant potential of adjunct treatment with DHEA in patients with TRD.

Primary objective 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 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 se-verity to a greater extent than adjunct placebo in subjects with TRD. Furthermore, changes in glucose, glycosylated hemoglobin (HbA1c), total, HDL- and LDL-cholesterol, C-reactive protein (CRP), and inter-leukin-6 levels from baseline to week 6 will be determined.

Being tested
Dehydroepiandrosterone (DHEA), Placebo
Keywords
TRD, DHEA, MDD
Medical subject headings
Depressive Disorder, Treatment-Resistant

What participants receive

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

  • Dehydroepiandrosterone (DHEA)Drug

    Dehydroepiandrosterone (DHEA) will be administered orally at a fixed dose of 100 mg/day for 6 weeks as add-on treatment to continued standard antidepressant monotherapy. Standard antidepressant medication will be continued at an unchanged dose throughout the treatment period.

  • PlaceboDrug

    Matching placebo capsules, indistinguishable from the investigational product, will be administered orally for 6 weeks as add-on treatment to continued standard antidepressant monotherapy.

Study groups in NCT07843927
Study groupRoleWhat they receive
DHEAExperimental100 mg/d DHEA to continued standard antidepressant medication
Receives: Drug: Dehydroepiandrosterone (DHEA)
PlaceboPlacebo comparatorPlacebo to continued standard antidepressant medication
Receives: Drug: Placebo

What is being measured

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

  1. Change score in MADRS (Montgomery-Asberg-Depression Rating Scale)

    The MADRS is a rating scale to measure depression severity. Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where higher MADRS scores indicate higher levels of depressive symptoms.

    Measured: 6 weeks

Secondary outcomes (2)

  1. MADRS response and remission

    MADRS response (defined as 50 % MADRS score reduction)

    MADRS remission (defined as MADRS score < 10)

    Measured: 6 weeks

  2. Adverse event-related treatment discontinuation

    Number and proportion of participants who discontinue study treatment due to an adverse event. Unit of Measure: Number and percentage of participants

    Measured: 6 weeks

Timeline

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

  1. First posted28 Sep 2026
  2. Study start22 Jun 2026
  3. Primary completion30 Sep 2028 (estimated)
  4. Study completion30 Sep 2028 (estimated)

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
320 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07843927
Sponsor's protocol ID
DARE-Trial - OT 209/19-1
Other IDs
2024-517963-21-00
Acronym
DARE
Status last verified
Sep 2026
First submitted
8 Sep 2026
Last updated
28 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Dehydroepiandrosterone (DHEA) in people with Treatment Resistant Depression (TRD), run by Charite University, Berlin, Germany at 9 sites 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 8 inclusion and 31 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: looking for participants now, as of the sponsor's last update on 28 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

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

Contact Christian Otte, MD (0049 30 450 617615, christian.otte@charite.de), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change score in MADRS (Montgomery-Asberg-Depression Rating Scale) (time frame: 6 weeks). 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 NCT07843927.

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 28 Sep 2026.

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