Treatment Resistant Depression (TRD)Phase 4NCT07080723
Algorithm Guided Treatment Versus Treatment as Usual (TAU) for Patients With Treatment Resistant Depression
A Phase 4 study testing Algorithm guided treatment (AGT) and Treatment as usual (TAU) in people with Treatment Resistant Depression (TRD), run by Aalborg University Hospital at 1 site in Denmark.
Trial summary
The trial utilizes a pragmatic, randomized, open label design with two parallel arms. Participants aged 18-65 with a diagnosis of unipolar depressive disorder and without stable remission in the past 12 months are randomized 1:1 to receive either algorithm guided treatment (AGT) or treatment as usual (TAU). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression (TRD)
- What is being tested?
- Algorithm guided treatment (AGT) and Treatment as usual (TAU)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteDenmark
- Study dates
- 13 Aug 2025to Jun 2027
- Phase
- Phase 4
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- A diagnosis of unipolar depressive disorder according to ICD-10 based on documented completion of the Mini International Neuropsychiatric Interview, version 7.0.2 (MINI 7.0.2) at Screening and confirmed by medical records or a healthcare professional.
- Have not achieved stable remission of depression in 12 months at investigator's clinical assessment.
- Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).
- Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.
- Signed document of informed consent.
- The participant is an outpatient.
- No significant change in medical treatment in the last 4 weeks before screening visit.
- The patient is pharmacologically treated for depression.
Who cannot join
- A diagnosis of dementia.
- Substance misuse influencing study participation as judged by the investigator.
- High risk of non-adherence at the investigator's discretion.
- Not understanding the Danish language as judged by the investigator.
- Suicidality according to C-SSRS with a positive response to question 4 or 5 within the last three months or upon investigator's discretion.
- Medical conditions such as cancer, kidney failure, epilepsy, deep brain stimulation device, or other medical conditions interfering with study the outcome and safety as judged by investigator's discretion.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Aalborg University Hospital
Aalborg, 9000
Deni Rkman, MD, +4593856194, deni.rkman@rn.dk
Simon Johansen, MsN, +4561395631, simon.johnsen@rn.dk
About this study
The trial utilizes a pragmatic, randomized, open label design with two parallel arms. Participants aged 18-65 with a diagnosis of unipolar depressive disorder and without stable remission in the past 12 months are randomized 1:1 to receive either algorithm guided treatment (AGT) or treatment as usual (TAU). The AGT approach incorporates pre-defined treatment steps, critical decision points, and "if-then" rules based on symptom response. It leverages prior treatment history, current symptomatology, and tolerability profiles to personalize the therapeutic sequence and reduce treatment inertia. In contrast, TAU reflects standard clinical practice, where treatment decisions are left to clinician discretion without algorithmic structure. The primary objective of the study is to determine whether AGT leads to a greater reduction in depressive symptoms over a 12-week treatment period, as measured by the 6-item Hamilton Depression Rating Scale (HAMD-6). Secondary objectives include evaluating cognitive and psychosocial functioning, suicide risk, treatment adherence, tolerability, number of medication changes, and long-term outcomes at a 24-week follow-up, providing insights into the longer-term trajectory of TRD management.
Read the detailed description
The study period consists of 12 weeks in the randomized phase and 12-week extended follow up period during which all participants are monitored and treated at the clinician's discretion. After baseline, study visits are planned at 4, 8, 12 and 24 weeks.
- Conditions
- Treatment Resistant Depression (TRD)
- Being tested
- Algorithm guided treatment (AGT), Treatment as usual (TAU)
- Keywords
- Algorithm guided treatment, AGT, ALGO, Treatment as usual, TAU, Treatment resistant depression, TRD, Depression
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Algorithm guided treatment (AGT)Other
AGTs consist of strategies (which treatments to use), tactics (how to implement each treatment) and treatment steps (in what order to implement the different treatments). Furthermore, AGTs also define critical decision points during the treatment at which the effects of a certain treatment are assessed and based on this assessment recommend specific treatment revisions according to preset "if-then rules." This is most often done by implementing measurement-based care.
TAU includes the standard clinical care for patients with TRD as determined by a senior consultant.
| Study group | Role | What they receive |
|---|---|---|
| Algorithm guided treatment (AGT) | Experimental | Treatment choice is defined in the AGT group by predetermined steps and critical decision points. The critical decision point moment is predetermined and marks the patient's outpatient visit. At these timepoint, HAMD score is determined and change from last visit is calculated, and based on this evaluation, specific treatment revisions are made following established "if-then" decision rules. This implies that the subsequent step is determined by the outcome of the assessment. If the patient's condition is assessed satisfactory, one step is selected and if the desired outcome is not achieved, an alternative step is pursued. Treatment choice for each step is based on patients medical history, previous therapy effect, adverse events, evidence based medicine and is selected a priori when patients are randomized by discussion with a senior consultant. AGT consists of which treatments to use at each step, how to implement each treatment and in what order to implement different treatments. Receives: Other: Algorithm guided treatment (AGT) |
| Treatment as usual (TAU) | Active comparator | TAU group treatment is defined and supervised by senior consultants with an experience in a treatment of patients with treatment resistant depression. Receives: Other: Treatment as usual (TAU) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hamilton Depression Scale, 6 item version (HAMD-6)
The primary outcome measure is the Hamilton Depression Scale, 6 item version (HAMD-6), used as a continuous variable. The primary outcome is the difference in differences (DID) between patients randomized to receive algorithm-guided treatment as compared to treatment as usual, as measured by HAMD-6, based on the mITT population.
The 6-item version of the Hamilton Depression Rating Scale ranges from 0 to 22, with higher scores indicating a worse outcome.
Measured: From baseline to end of study (12 weeks)
Secondary outcomes (17)
HAMD-17
All secondary outcomes are based on the mITT population unless otherwise specified. A Per Protocol (PP) analysis at 12 weeks and at the end of follow-up is performed for all continuous secondary outcomes.
Difference-in-difference in HAMD-17. The 17-item version of the Hamilton Depression Rating Scale ranges from 0 to 52, with higher scores indicating a worse outcome.
Measured: Up to 24 weeks
HAMD-6
Difference-in-difference in HAMD-6 for the PP12 and the PP24 population. The 6-item version of the Hamilton Depression Rating Scale ranges from 0 to 22, with higher scores indicating a worse outcome.
Measured: Up to 24 weeks
UKU
Difference in difference in UKU adverse events scale
Measured: Up to 24 weeks
SCIP
Difference-in-difference in Screen for Cognitive Impairment in Psychiatry (SCIP).
Values range from 0 to 64+, higher scores indicating a better outcome.
Measured: Up to 12 weeks
FAST
Difference-in-difference in the Functioning Assessment Short Test (FAST). Values range from 0 to 72, higher scores indicating a worse outcome).
Measured: Up to 12 weeks
COBRA
Difference in difference in Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA). Values range from 0 to 48, higher scores indicating a worse outcome.
Measured: Up to 12 weeks
CGI
Difference in difference in the Clinical Global Impression Scale (CGI). Values range from 1 to 7, higher scores indicating a worse outcome.
Measured: Up to 12 weeks
C-SSRS
Difference in difference in the Columbia-Suicide Severity Rating Scale (C-SSRS).
Values range from 1 to 5, higher scores indicating a worse outcome.
Measured: Up to 12 weeks
Between-groups difference in proportion of responders and remitters in HAMD-6 score
Responders are defined as subjects with a reduction of at least 50 % in their HAMD-6 scores between baseline and the endpoint of interest. Remitters are defined as subjects with HAMD-6 score below 5 at the endpoint of interest. Both are measured at 8 weeks or at a premature endpoint before last-observation-carried-forward (LOCF) and at 12 weeks or at a premature endpoint before LOCF.
Measured: Week 8 and 12
Between-group differences in reason for all cause treatment discontinuation
Between-group differences in reason for all cause treatment discontinuation (lack of effect, lack of tolerability, lost to follow-up, or other cause)
Measured: Up to 24 weeks
Between-group differences in time to all cause treatment discontinuation
Between-group differences in time to all cause treatment discontinuation
Measured: Up to 24 weeks
Between-group differences in number of changes in treatment strategies
Between-group differences in number of changes in treatment strategies
Measured: Up to 12 weeks
Between-group differences in number of changes in the number of different prescribed medications over the treatment period
Between-group differences in number of changes in the number of different prescribed medications over the treatment period
Measured: Up to 12 weeks
Between-group difference for the ITT population in reasons for premature discontinuation
Between-group difference for the ITT population in reasons for premature discontinuation
Measured: Up to 24 weeks
Between-group difference for the ITT population in reasons for time to all cause discontinuation
Between-group difference for the ITT population in reasons for time to all cause discontinuation
Measured: Up to 24 weeks
Between-group difference for the ITT population in adverse events and serious adverse events
Between-group difference for the ITT population in adverse events and serious adverse events
Measured: Up to 12 weeks
Between-groups difference from original randomization in proportion of responders and remitters at end of follow-up
Between-groups difference from original randomization in proportion of responders and remitters at end of follow-up
Measured: Up to 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jul 2025
- Study start13 Aug 2025
- Primary completionJun 2027 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant Depression (TRD)Studies of the same condition, open and under way.
- More trials run by Aalborg University HospitalThe 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Aalborg University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, René Ernst Nielsen, Aalborg University Hospital
- Investigators
- René Ernst Nielsen, Prof., MD, PhD, Principal investigator, Aalborg University Hospital, Psychiatry, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07080723
- Sponsor's protocol ID
- N-20250007
- Status last verified
- Jun 2025
- First submitted
- 7 Jul 2025
- Last updated
- 27 Apr 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Algorithm Guided Treatment Versus Treatment as Usual (TAU) for Patients With Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT07080723
- Acronym / sponsor ID
- N-20250007
- Conditions
- Treatment Resistant Depression (TRD)
- Keywords
- Algorithm guided treatment, AGT, ALGO, Treatment as usual, TAU, Treatment resistant depression, TRD, Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Aalborg University HospitalUniversity, hospital or other
- Study start
- 13 Aug 2025 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 23 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The trial utilizes a pragmatic, randomized, open label design with two parallel arms. Participants aged 18-65 with a diagnosis of unipolar depressive disorder and without stable remission in the past 12 months are randomized 1:1 to receive either algorithm guided treatment (AGT) or treatment as usual (TAU). The AGT approach incorporates pre-defined treatment steps, critical decision points, and "if-then" rules based on symptom response. It leverages prior treatment history, current symptomatology, and tolerability profiles to personalize the therapeutic sequence and reduce treatment inertia. In contrast, TAU reflects standard clinical practice, where treatment decisions are left to clinician discretion without algorithmic structure. The primary objective of the study is to determine whether AGT leads to a greater reduction in depressive symptoms over a 12-week treatment period, as measured by the 6-item Hamilton Depression Rating Scale (HAMD-6). Secondary objectives include evaluating cognitive and psychosocial functioning, suicide risk, treatment adherence, tolerability, number of medication changes, and long-term outcomes at a 24-week follow-up, providing insights into the longer-term trajectory of TRD management.
Detailed description
The study period consists of 12 weeks in the randomized phase and 12-week extended follow up period during which all participants are monitored and treated at the clinician's discretion. After baseline, study visits are planned at 4, 8, 12 and 24 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Algorithm guided treatment (AGT) | Experimental | Other: Algorithm guided treatment (AGT)Treatment choice is defined in the AGT group by predetermined steps and critical decision points. The critical decision point moment is predetermined and marks the patient's outpatient visit. At these timepoint, HAMD score is determined and change from last visit is calculated, and based on this evaluation, specific treatment revisions are made following established "if-then" decision rules. This implies that the subsequent step is determined by the outcome of the assessment. If the patient's condition is assessed satisfactory, one step is selected and if the desired outcome is not achieved, an alternative step is pursued. Treatment choice for each step is based on patients medical history, previous therapy effect, adverse events, evidence based medicine and is selected a priori when patients are randomized by discussion with a senior consultant. AGT consists of which treatments to use at each step, how to implement each treatment and in what order to implement different treatments. |
| Treatment as usual (TAU) | Active comparator | Other: Treatment as usual (TAU)TAU group treatment is defined and supervised by senior consultants with an experience in a treatment of patients with treatment resistant depression. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- A diagnosis of unipolar depressive disorder according to ICD-10 based on documented completion of the Mini International Neuropsychiatric Interview, version 7.0.2 (MINI 7.0.2) at Screening and confirmed by medical records or a healthcare professional.
- Have not achieved stable remission of depression in 12 months at investigator's clinical assessment.
- Severity of depression: A score of at least 21 on the self-reported Major Depression Inventory (MDI).
- Age criteria: Subjects must be at least 18 years old and below 65 at the time of randomization.
- Signed document of informed consent.
Key exclusion criteria (6 listed)
- A diagnosis of dementia.
- Substance misuse influencing study participation as judged by the investigator.
- High risk of non-adherence at the investigator's discretion.
- Not understanding the Danish language as judged by the investigator.
- Suicidality according to C-SSRS with a positive response to question 4 or 5 within the last three months or upon investigator's discretion.
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 |
|---|---|---|
| Algorithm guided treatment (AGT)AGTs consist of strategies (which treatments to use), tactics (how to implement each treatment) and treatment steps (in what order to implement the different treatments). Furthermore, AGTs also define critical decision points during the treatment at which the effects of a certain treatment are assessed and based on this assessment recommend specific treatment revisions according to preset "if-then rules." This is most often done by implementing measurement-based care. | Other | Algorithm guided treatment (AGT) |
| Treatment as usual (TAU)TAU includes the standard clinical care for patients with TRD as determined by a senior consultant. | Other | Treatment as usual (TAU) |
Primary outcome
Hamilton Depression Scale, 6 item version (HAMD-6)
Time frame: From baseline to end of study (12 weeks)
The primary outcome measure is the Hamilton Depression Scale, 6 item version (HAMD-6), used as a continuous variable. The primary outcome is the difference in differences (DID) between patients randomized to receive algorithm-guided treatment as compared to treatment as usual, as measured by HAMD-6, based on the mITT population. The 6-item version of the Hamilton Depression Rating Scale ranges from 0 to 22, with higher scores indicating a worse outcome.
17 secondary outcomes
HAMD-17
Time frame: Up to 24 weeks
HAMD-6
Time frame: Up to 24 weeks
UKU
Time frame: Up to 24 weeks
SCIP
Time frame: Up to 12 weeks
FAST
Time frame: Up to 12 weeks
COBRA
Time frame: Up to 12 weeks
CGI
Time frame: Up to 12 weeks
C-SSRS
Time frame: Up to 12 weeks
Between-groups difference in proportion of responders and remitters in HAMD-6 score
Time frame: Week 8 and 12
Between-group differences in reason for all cause treatment discontinuation
Time frame: Up to 24 weeks
Between-group differences in time to all cause treatment discontinuation
Time frame: Up to 24 weeks
Between-group differences in number of changes in treatment strategies
Time frame: Up to 12 weeks
Between-group differences in number of changes in the number of different prescribed medications over the treatment period
Time frame: Up to 12 weeks
Between-group difference for the ITT population in reasons for premature discontinuation
Time frame: Up to 24 weeks
Between-group difference for the ITT population in reasons for time to all cause discontinuation
Time frame: Up to 24 weeks
Between-group difference for the ITT population in adverse events and serious adverse events
Time frame: Up to 12 weeks
Between-groups difference from original randomization in proportion of responders and remitters at end of follow-up
Time frame: Up to 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2026.
- Individual participant dataSharing planned: No
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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.
René Ernst Nielsen, Prof., MD, PhD principal investigator
Aalborg University Hospital, Psychiatry, Denmark
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Algorithm guided treatment (AGT) and Treatment as usual (TAU) in people with Treatment Resistant Depression (TRD), run by Aalborg University Hospital at 1 site in Denmark.
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 6 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 27 Apr 2026. 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 Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 Deni Rkman, MD (+4593856194, deni.rkman@rn.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hamilton Depression Scale, 6 item version (HAMD-6) (time frame: From baseline to end of study (12 weeks)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 27 Apr 2026.