AIDA-DEP - Accelerated Intermittent theta-burst stimulation with D-cycloserine Augmentation for DEPression - a multicenter, randomized, placebo-controlled, double-blind clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Uppsala

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

8 Jan 2026 → ongoing

Decision date (initial)

2025-09-15

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of this trial is to evaluate the efficacy of adding a daily oral dose of 100 mg D-cycloserine for major depressive disorder (MDD) compared to placebo during a nine weekday long treatment course of aiTBS assessed as the difference between groups in changes in depressive symptoms in the following PICO Population: >18 years old, with a current depressive episode (Montgomery-Asberg Depression Rating Scale [MADRS]-score >19).

Secondary objectives 1

1. The secondary objectives of this trial are to evaluate the efficacy of adding a daily oral dose of 100 mg D-cycloserine for major depressive disorder (MDD) compared to placebo during a nine weekday long treatment course of aiTBS in the PICO population defined above on other associated psychiatric symptoms, function, health perception, cognitive function (THINC-it) and neurophysiological brain-functioning as measured with resting state Electroencephalography (EEG) and with frontal functional near-infrared spectroscopy (fNIRS).

Conditions and MedDRA coding

Major Depression

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. The subject has given their written consent to participate in the trial.
2. Are at least 18 years old at the time of written informed consent
3. Are able to read, speak, and understand Swedish
4. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations
5. Are able to swallow capsules
6. Meet ICD-10 criteria for a diagnosis of a major depressive disorder and are currently experiencing a major depressive episode of at least a 30-day duration at the time of the screening
7. Have sustained moderate-severe depression symptoms at screening, as defined by a screening MADRS total score ≥ 20.
8. Failure to achieve clinical response with at least one adequate trial of a first line antidepressant medication or psychotherapy.
9. Unchanged antidepressant medications for 4 weeks prior to enrollment and the patient have no intention of changing medications during the first 28 days of the study.
10. For female subjects of fertile age, adequate contraception should be used.
11. Signed informed consent

Exclusion criteria 16

1. Have intracardial lines (pacemaker or ICD) intracranial metallic implant
2. Have an unstable medical condition
3. Have epilepsy
4. Have renal failure
5. Have porphyria
6. Use bensodiazepines
7. Use dextrometorphan
8. Use memantine
9. Use ketamine
10. Current pregnancy, or intend to become pregnant during the study or who are currently nursing.
11. Currently receive electroconvulsive therapy (ECT)
12. Meet ICD-10 criteria for schizophrenia spectrum or other psychotic disorders, including MDD with psychotic features (except substance/medication-induced or due to another medical condition), or Bipolar I Disorder, Bipolar II Disorder and bipolar disorder NOS, or a lifetime diagnosis of schizophrenia spectrum or other psychotic disorders
13. Meet ICD-10 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine & nicotine). Participants with a diagnosis of alcohol or drug use disorder within the past 3 months will be excluded
14. Have presence of any psychiatric condition or symptom judged by the PI (or designee) to be a more significant clinical problem than MDD for the participant
15. Have any physical or psychological symptom, medication or other relevant finding at Screening or Baseline, based on the clinical judgment of clinical/medical study personnel, that would make a participant unsuitable for the study
16. Have an allergy or intolerance to any of the materials contained in either drug product

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Between-group difference in change of blinded rater MADRS total score from baseline to Day 28 (21-35) after first treatment day (interview by blinded external rater via video consultation documented on item level in eCRF).

Secondary endpoints 5

1. Change in observer rated depressive symptoms (MADRS) to treatment day 12 and 180 and Clinical Global Impression (CGI) at day 12, 28, and 180
2. Response and remission rates at all time points on observer (MADRS) and self-rated depressive symptoms Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR)
3. Survival time to initiation of new antidepressant treatment, hospitalization or death during the whole study period (until day 180)
4. Change in score from baseline to Day 5, 12, 42, and 180 (end of study) self-rated depressive symptoms (QIDS-SR); Intensity in Suicidal Ideation from Columbia Suicide Severity Rating Scale (ISI-CSSR); anxiety symptoms, General Anxiety Disorder 7 (GAD-7); functioning, Sheehan Disability Scale (SDS); general health perception, EQ-5D-5L
5. Change in cognitive functioning (THINC-it); pre-attentive stimuli detection, Mismatch Negativity (MMN); frontal oxygenation (fNIRS); resting EEG measures including frequency spectra, microstates, and aperiodic activity.

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Uppsala

Sponsor organisation

Region Uppsala

Address

Storgatan 27, Uppsala Domkyrkofors Uppsala Domkyrkofors

City

Uppsala

Postcode

753 31

Country

Sweden

Scientific contact point

Organisation

Region Uppsala

Contact name

Robert Bodén

Public contact point

Organisation

Region Uppsala

Contact name

Robert Bodén

Locations

1 EU/EEA country · 6 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

Results and documents

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

Documents 21 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