Depressive Disorder, MajorPhase 1NCT03854578

A Study in People With Depression to Test the Effects of BI 1358894 on Parts of the Brain That Are Involved in Emotions

A Phase 1 study testing BI 1358894 and Citalopram in people with Depressive Disorder, Major, run by Boehringer Ingelheim 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

To assess the effect of a single dose of BI 1358894 compared to placebo on BOLD responses in modulating brain processing of emotional and cognitive stimuli on the amygdala and related brain structure using fMRI in in unmedicated patients with depression. Read more about this study

Who is it for?: Ages 18 to 45 years
Conditions the study is for: Depressive Disorder, Major
What is being tested?: BI 1358894 and Citalopram
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 73 participants
Where: 1 siteGermany
Study dates: 12 Mar 2019to 23 Sep 2019
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 45 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Patients having a diagnosis of a MDD according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) (single episode or recurrent) with a MADRS total score between ≥ 7 and < 26 at screening.
Male or female aged 18 to 45 years, inclusive at screening.
Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control.
Patients must be, in the opinion of the Investigator, capable of and eligible for completing the fMRI and tasks.
Patients must be right-handed.
Patients must have acceptable weight as defined by BMI (weight [kg]/height [m]²) range of 18 to 30 kg/m², inclusive at Visit 1.

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Patients must be a non-smoker or light smoker (≤ 5 cigarettes per day).
Patients must have signed the informed consent form prior to the first study-related procedure indicating they understand the purpose of and procedures required for the study and are willing to participate in the study.
Further inclusion criteria apply

Who cannot join

Meeting any diagnostic criteria for a major psychiatric disorder (other than MDD), as determined by DSM-V at screening.
Has received a prescribed medication (including antidepressants) within 28 days prior to Visit 1 (apart from the contraceptive pill) or having received over the counter medication (including pain killers) within 10 days prior to screening. Participants who have taken prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety.
Patients where it is foreseen (per investigator judgement) that a delay of initiation of standard of care therapy for the depressive disorder to 14 days after day 1 of Visit 2 is medically not justifiable.
A history of alcohol or substance dependence or abuse within the last 12 months from Visit 1.
Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 or 5 for ideation on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening or treatment visit.
Has a history of, or presents (in the opinion of the Investigator) with, significant neurological or psychiatric conditions (such as stroke, traumatic brain injury, seizures, space occupying lesions, multiple sclerosis, Parkinson's disease, vascular dementia, transient ischemic attack, schizophrenia, blackouts requiring hospitalisation).
A planned medical treatment within the study period that might interfere with the study procedures.
Further exclusion criteria apply

Trial locations and contacts

1 site in 1 country.

Germany1 site

Charité - Universitätsmedizin Berlin
Berlin, 10117

Other trials in Germany

About this study

Official title: A Single Dose, Randomized, Placebo Controlled Phase I Study on the Effects of BI 1358894 on Functional MRI Measurements in an Emotional Processing Paradigm in Patients With Major Depressive Disorder

Conditions: Depressive Disorder, Major
Being tested: BI 1358894, Placebo matching BI 1358894, Citalopram
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.

BI 1358894Drug
Film-coated tablet
Placebo matching BI 1358894Drug
Film-coated tablet
CitalopramDrug
Film-coated tablet

Study groups in NCT03854578
Study group	Role	What they receive
BI 1358894	Experimental	Not described Receives: Drug: BI 1358894
Citalopram	Experimental	Not described Receives: Drug: Citalopram
Placebo matching BI 1358894	Experimental	Not described Receives: Drug: Placebo matching BI 1358894

What is being measured

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

Mean Blood Oxygenation Level Depend (BOLD) Signal % Change in an Emotional Paradigm, Based on the Emotional Faces From the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP)
The primary endpoint was the mean BOLD signal % change in an emotional paradigm, based on the emotional faces from the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP) in the corticolimbic system comprising the following eight brain regions of interest:
- Amygdala left
- Amygdala right
- Dorsolateral prefrontal cortex left
- Dorsolateral prefrontal cortex right
- Insula left
- Insula right
- Anterior cingulate cortex left
- Anterior cingulate cortex right
Measured: A 50 min scan, 6 hours following drug intake.

Secondary outcomes (1)

Mean BOLD Signal % Change in an Emotional Paradigm in the Corticolimbic System Using the Affective Pictures of the Open Affective Standardised Image Set (OASIS).
The secondary endpoint was the mean BOLD signal % change in an emotional paradigm (affective picture set - OASIS task) in the corticolimbic system, consisting of eight brain regions:
- Amygdala left
- Amygdala right
- Dorsolateral prefrontal cortex left
- Dorsolateral prefrontal cortex right
- Insula left
- Insula right
- Anterior cingulate cortex left
- Anterior cingulate cortex right
Measured: A 50 min scan, 6 hours following drug intake.

Timeline

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

12 Mar 201923 Sep 2019

First posted26 Feb 2019
Study start12 Mar 2019
Primary completion27 Aug 2019
Study completion23 Sep 2019

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
More trials run by Boehringer IngelheimThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 73 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03854578
Sponsor's protocol ID: 1402-0003
Other IDs: 2017-004763-12, 2017
Status last verified: Feb 2025
First submitted: 25 Feb 2019
Last updated: 25 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

Publications

Grimm S, Keicher C, Paret C, Niedtfeld I, Beckmann C, Mennes M, Just S, Sharma V, Fuertig R, Herich L, Mack S, Thamer C, Schultheis C, Weigand A, Schmahl C, Wunder A. The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder. Eur Neuropsychopharmacol. 2022 Dec;65:44-51. doi: 10.1016/j.euroneuro.2022.10.009. Epub 2022 Nov 4.
PubMed 36343427

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 25 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Single Dose, Randomized, Placebo Controlled Phase I Study on the Effects of BI 1358894 on Functional MRI Measurements in an Emotional Processing Paradigm in Patients With Major Depressive Disorder
ClinicalTrials.gov ID: NCT03854578
Acronym / sponsor ID: 1402-0003
Conditions: Depressive Disorder, Major
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 73 participants (actual)
Lead sponsor: Boehringer IngelheimIndustry (pharma, biotech, devices)
Study start: 12 Mar 2019 (actual)
Primary completion: 27 Aug 2019 (actual)
Study completion: 23 Sep 2019 (actual)
First posted: 26 Feb 2019 (actual)
Results: Posted 25 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
BI 1358894	Experimental	Drug: BI 1358894
Citalopram	Experimental	Drug: Citalopram
Placebo matching BI 1358894	Experimental	Drug: Placebo matching BI 1358894

Who may qualify

Ages: 18 to 45 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (9 listed)

Patients having a diagnosis of a MDD according to Diagnostic and Statistical Manual of Mental Disorders-V (DSM-V) (single episode or recurrent) with a MADRS total score between ≥ 7 and < 26 at screening.
Male or female aged 18 to 45 years, inclusive at screening.
Male or female patients. Women of childbearing potential (WOCBP) and men able to father a child must be ready and able to use highly effective methods of birth control.
Patients must be, in the opinion of the Investigator, capable of and eligible for completing the fMRI and tasks.
Patients must be right-handed.

Key exclusion criteria (8 listed)

Meeting any diagnostic criteria for a major psychiatric disorder (other than MDD), as determined by DSM-V at screening.
Has received a prescribed medication (including antidepressants) within 28 days prior to Visit 1 (apart from the contraceptive pill) or having received over the counter medication (including pain killers) within 10 days prior to screening. Participants who have taken prescription medication may still be entered into the study, if, in the opinion of the Investigator, the medication received will not interfere with the study procedures or compromise safety.
Patients where it is foreseen (per investigator judgement) that a delay of initiation of standard of care therapy for the depressive disorder to 14 days after day 1 of Visit 2 is medically not justifiable.
A history of alcohol or substance dependence or abuse within the last 12 months from Visit 1.
Has a current or recent history of clinically significant suicidal ideation within the past 6 months, corresponding to a score of 4 or 5 for ideation on the C-SSRS, or a history of suicidal behavior within the past year, as validated by the C-SSRS at screening or treatment visit.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
BI 1358894Film-coated tablet	Drug	BI 1358894
Placebo matching BI 1358894Film-coated tablet	Drug	Placebo matching BI 1358894
CitalopramFilm-coated tablet	Drug	Citalopram

Primary outcome

Mean Blood Oxygenation Level Depend (BOLD) Signal % Change in an Emotional Paradigm, Based on the Emotional Faces From the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP)
Time frame: A 50 min scan, 6 hours following drug intake.
The primary endpoint was the mean BOLD signal % change in an emotional paradigm, based on the emotional faces from the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP) in the corticolimbic system comprising the following eight brain regions of interest: * Amygdala left * Amygdala right * Dorsolateral prefrontal cortex left * Dorsolateral prefrontal cortex right * Insula left * Insula right * Anterior cingulate cortex left * Anterior cingulate cortex right

1 secondary outcome

Mean BOLD Signal % Change in an Emotional Paradigm in the Corticolimbic System Using the Affective Pictures of the Open Affective Standardised Image Set (OASIS).
Time frame: A 50 min scan, 6 hours following drug intake.

Results and safety

Results posted to the registry on 25 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Matching to BI 1358894	24	24
Citalopram	24	24
BI 1358894	25	25

Primary outcome: Mean Blood Oxygenation Level Depend (BOLD) Signal % Change in an Emotional Paradigm, Based on the Emotional Faces From the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP)

Time frame: A 50 min scan, 6 hours following drug intake.. Mean (Standard Deviation). Unit: Percent change

Measure	Placebo Matching to BI 1358894 n = 24	Citalopram n = 23	BI 1358894 n = 22
Amygdala left	0.305 (0.119)	0.290 (0.134)	0.223 (0.093)
Amygdala right	0.364 (0.136)	0.291 (0.146)	0.282 (0.071)
Dorsolateral prefrontal cortex left	0.065 (0.146)	0.044 (0.111)	0.049 (0.109)
Dorsolateral prefrontal cortex right	0.131 (0.202)	0.117 (0.183)	0.125 (0.105)
Insula left	0.162 (0.146)	0.110 (0.107)	0.075 (0.126)
Insula right	0.157 (0.133)	0.137 (0.107)	0.1205 (0.125)
Anterior cingulate cortex left	0.003 (0.121)	-0.027 (0.074)	-0.024 (0.085)
Anterior cingulate cortex right	-0.008 (0.131)	-0.026 (0.087)	-0.018 (0.101)

Placebo Matching to BI 1358894 vs BI 1358894: Mean change: -0.08 (90% CI -0.14 to -0.03), p = 0.0105, ANOVA
Placebo Matching to BI 1358894 vs BI 1358894: Mean change: -0.08 (90% CI -0.14 to -0.03), p = 0.0134, ANOVA
Placebo Matching to BI 1358894 vs BI 1358894: Mean change: -0.03 (90% CI -0.08 to 0.02), p = 0.3495, ANOVA

Population analysed: Evaluable set (ES): This patient set included all randomised patients who performed the functional Magnetic Resonance Imaging (fMRI) measurements and did not experience severe headaches directly before or during the fMRI measurements. In particular, patients who had to be replaced due to severe headaches were excluded from the ES.

1 secondary outcome is reported in the full results.

Adverse events

Time frame: From the time of administration of BI 1358894 or BI-matching placebo (in the placebo and Citalopram arm) until time of administration of BI 1358894 or BI-matching placebo + Residual effect period(14*24 h) or 0:00 AM on day after subject's trial termination date, whatever occurs earlier. Up to 14 days.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Placebo Matching to BI 1358894	0 of 25 (0%)	13 of 25 (52%)	0 of 25
Citalopram	0 of 23 (0%)	13 of 23 (56.5%)	0 of 23
BI 1358894	0 of 23 (0%)	21 of 23 (91.3%)	0 of 23
BI 1358894 +Citalopram	0 of 2 (0%)	2 of 2 (100%)	0 of 2

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36343427Grimm S, Keicher C, Paret C, Niedtfeld I, Beckmann C, Mennes M, Just S, Sharma V, Fuertig R, Herich L, Mack S, Thamer C, Schultheis C, Weigand A, Schmahl C, Wunder A. The effects of transient receptor potential cation channel inhibition by BI 1358894 on cortico-limbic brain reactivity to negative emotional stimuli in major depressive disorder. Eur Neuropsychopharmacol. 2022 Dec;65:44-51. doi: 10.1016/j.euroneuro.2022.10.009. Epub 2022 Nov 4.
Individual participant dataSharing planned: No. Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: https://www.mystudywindow.com/msw/datasharing

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BI 1358894 and Citalopram in people with Depressive Disorder, Major, run by Boehringer Ingelheim 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 9 inclusion and 8 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 25 Feb 2025. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Mean Blood Oxygenation Level Depend (BOLD) Signal % Change in an Emotional Paradigm, Based on the Emotional Faces From the Warsaw Set of Emotional Facial Expression Pictures (WSEFEP) (time frame: A 50 min scan, 6 hours following drug intake.). 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 NCT03854578, which also lists 1 linked publication.

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 25 Feb 2025.