Resistant Depression, TreatmentTRACE-RMDNCT05136027
TReAtment With CombinedExercise in Patients With Resistant Major Depression
A study testing Combined training in people with Resistant Depression, Treatment, run by University of the Basque Country (UPV/EHU) at 1 site in Spain.
Trial summary
Major depressive disorder is one of the most prevalent and disabling mental disorders worldwide. Forty percent of people with major depressive disorder are in moderate remission, with the remainder meeting the criteria for treatment-resistant depressive disorder (TRD), with an inadequate response to at least two… Read more about this study
- Who is it for?
- Ages 18 to 78 years
- Conditions the study is for
- Resistant Depression, Treatment
- What is being tested?
- Combined training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteSpain
- Study dates
- 30 Dec 2022to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 78 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Depression major disorder.
- 2 or more antdepressives resistant a treatment.
- Consent informed signed
Who cannot join
- Schizophrenia or other disorders.
- Suicide risk.
- Unstable medic illness or unsuitable controlled.
- Disorder for use of active substances.
- Comorbidity with other psychiatric pathologies.
- Montreal Cognitive Assessment <26/30, cognitive deterioration.
- Incapacity for realizing physical exercise because of osteoarticular, cardiovascular, or metabolic difficulty.
Trial locations and contacts
1 site in 1 country.
Spain1 site, 1 recruiting
- Recruiting
Basque Country University
Vitoria-Gasteiz
Sara Maldonado-Martín, 34945013534, sara.maldonado@ehu.eus
About this study
Official title: Exercise Program in Patients With Treatment-resistant Depressive Disorder Compared to Usual Practice
Major depressive disorder is one of the most prevalent and disabling mental disorders worldwide. Forty percent of people with major depressive disorder are in moderate remission, with the remainder meeting the criteria for treatment-resistant depressive disorder (TRD), with an inadequate response to at least two different antidepressants of adequate dose and duration. Dysfunctionality in these individuals is frequent and severe and its importance contrasts with the absence of drugs to alleviate these deficits. Exercise programs, which were initially developed as interventions aimed at improving physical health in early stages or in mild symptomatology, have shown that they can also improve the symptoms of this disease in more advanced stages There is evidence of new therapeutic interventions for TRD. New pharmacological targets that aim to improve the evolution of depression and its functional repercussions augur that, in the future, new drugs will have to be combined with other therapeutic strategies, including exercise. Therefore, the objectives of this clinical trial with a control group are: 1) to analyze the changes in depressive symptoms in people diagnosed with TRD included in the exercise program compared to a control group; 2) to evaluate the improvement in physical health through cardiovascular risk factors and life expectancy suffered by this sector of the population, and 3) to analyze changes in functional status and quality of life. This is a prospective longitudinal intervention design (three months) in which people with TRD are included in two groups: 1) intervention with exercise (two days/week) and 2) control care with usual treatment. The aim is to find an improvement in mood and functionality with the implementation of exercise, as well as changes in physical areas such as blood pressure or body mass index, which are considered predictive factors of cardiovascular disease.
Read the detailed description
The presence of major depressive disorder (MDD) in today's society is worryingly high. Specifically, the prevalence-year prevalence of MDD in Spain is 3.9% and lifetime prevalence is 10.5%. The lifetime prevalence for men is 6.29% and 14.47% for women in Spain according to the ESEMED-Spain study. Although there is no explicit international consensus, the medical literature and research define treatment-resistant depression (TRD) as any MDD that does not respond to two trials of treatment antidepressant treatment at adequate doses and for an adequate duration of time.
MDD is the leading cause of years lived with disability worldwide, accounting for 11.9%. It has been estimated that during the year 2020 it could be second only to ischemic heart disease in disability-adjusted life years lost. Given this bleak scenario, different non-pharmacological strategies have been considered as possible complementary treatments to pharmacological treatment to help improve the prognosis of MDD and remission rates, such as exercise and electroconvulsive therapy.
Sedentary lifestyles are a very common feature in the severely mentally disordered population. One of the causes for this to occur is that people with MDD have very little confidence in their ability to exercise and lack the necessary social support. This inactivity together with other modifiable risk factors such as tobacco use, high blood pressure, and overweight/obesity, in addition to the side effects of pharmacological treatments contributes to the appearance of different diseases, as well as decreased life expectancy and quality of life. TRD can act as a cause or as a repercussion of physical inactivity.
It has been recognized for several years that the performance of regular exercise is cardioprotective, decreasing the incidence of cardiovascular diseases such as arterial hypertension, coronary artery disease, type 2 diabetes, and atherosclerosis. In addition to being cardioprotective, exercise has shown a positive association with psychological well-being and therapeutic benefits in older people with depressive disorder, depressive symptoms in patients with Alzheimer's disease and MDD.
Although there is still some controversy about the intensity and frequency of exercise, and the duration of the exercise program, the recommendations were the adoption of a moderate-intensity exercise program of at least 30 minutes on most days of the week, for 10-12 weeks. In the latest World Health Organization guidelines on physical activity (PA) and sedentary habits, for the improvement of quality of life in adults with TMD the general recommendations do not differ from the general population, i.e., people should accumulate throughout the week a minimum of 150-300 minutes of moderate aerobic PA or a minimum of 75-150 minutes of vigorous PA, or an equivalent combination of both in order to obtain notable health benefits. Also, in order to achieve additional health benefits, the participants should perform two days a week of moderate or higher intensity muscle-strengthening activities.
- Conditions
- Resistant Depression, Treatment
- Being tested
- Combined training
- Keywords
- Depression, Exercise, Low-intensity Interval Training, Resistance Training
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depression, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Combined trainingOther
Low-intensity interval training and resistance exercise
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Intervention group: In the exercise session will carry out a combined training in four parts, low- intensity interval training in a bicycle, resistance circuit training, low- intensity interval training in a bicycle, and CORE exercises. Receives: Other: Combined training |
| Attention Control | No intervention | Regular in-hospital treatment with occupational activity sessions with the same frequency and duration as the intervention group. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depressión Rating Scale (MADRS)
Ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.
Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60.
Usual cutoff points are:
0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression
Measured: 12 weeks
Cardiorespiratory fitness
Cardiorespiratory fitness evaluation measured by cardiopulmonary exercise test. Maximu oxygen uptake measured in mL/kg/min or L/min is the gold standard variable.
Measured: 12 weeks
Secondary outcomes (3)
Clinical Global Impression Scale (CGI)
The Clinical Global Impression (CGI) rating scales are measures of symptom severity, treatment response and the efficacy of treatments in treatment studies of patients with mental disorders. Its 3 items assess, 1) Severity of Illness (CGI-S), 2) Global Improvement (CGI-I), and 3) Efficacy Index (CGI-E, which is a measure of treatment effect and side effects specific to drugs that were administered).
Measured: 12 weeks
Sheehan Disability Scale (SDS)
five-item, self-rated questionnaire designed to measure the extent to which a patient's disability due to an illness or health problem interferes with work/school, social life/leisure activities, and family life/home responsibilities.
Total score 0-30 (0 unimpaired, 30 highly impaired) Work/school (0-10) Social life (0-10) Family life/home responsibilities (0-10 Scores of ≥5 on any of the 3 scales; high scores are associated with significant functional impairment.
Measured: 12 weeks
Treatment Satisfaction Questionnaire for Medication - 9 items (TSQM-9)
To measure patients' satisfaction with medication
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2021
- Study start30 Dec 2022
- Primary completion30 Nov 2024 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Resistant Depression, TreatmentStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Exercise group Atenttion Control
- Masking
- Single blind
- Who is masked
- Care provider
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of the Basque Country (UPV/EHU)
- Sponsor type
- University, hospital or other
- Collaborators
- Red Salud Mental Araba
- Responsible party
- Principal investigator, SARA MALDONADO-MARTIN, University of the Basque Country (UPV/EHU)
- Investigators
- NAGORE IRIARTE-YOLLER, MD, Principal investigator, PSYCHIATRIC HOSPITAL OF ÁLAVA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05136027
- Sponsor's protocol ID
- TRACE-RMD study
- Acronym
- TRACE-RMD
- Status last verified
- Dec 2023
- First submitted
- 1 Nov 2021
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: A protocol paper will be written once the clinical trials identification number will be defined
Publications
Tous-Espelosin M, Pavon-Navajas C, Etxaniz-Oses J, Canas-Garcia MT, Maldonado-Martin S, Orruno-Vivar J, Corres P, Iriarte-Yoller N. Effects of combined exercise training for adults with resistant major depression: a pilot study from the TRACE-RMD project. PeerJ. 2025 Nov 17;13:e20356. doi: 10.7717/peerj.20356. eCollection 2025.
PubMed 41282982Iriarte-Yoller N, Etxaniz-Oses J, Pavon-Navajas C, Tous-Espelosin M, Sanchez-Gomez PM, Maldonado-Martin S, Yoller-Elburgo AB, Elizagarate-Zabala E. Treatment with combined exercise in patients with resistant major depression (TRACE-RMD): study protocol for a randomised controlled trial. Trials. 2024 Dec 18;25(1):827. doi: 10.1186/s13063-024-08685-7.
PubMed 39696604
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exercise Program in Patients With Treatment-resistant Depressive Disorder Compared to Usual Practice
- ClinicalTrials.gov ID
- NCT05136027
- Acronym / sponsor ID
- TRACE-RMD / TRACE-RMD study
- Conditions
- Resistant Depression, Treatment
- Keywords
- Depression, Exercise, Low-intensity Interval Training, Resistance Training
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 70 participants (estimated)
- Lead sponsor
- University of the Basque Country (UPV/EHU)University, hospital or other
- Collaborators
- Red Salud Mental Araba
- Study start
- 30 Dec 2022 (actual)
- Primary completion
- 30 Nov 2024 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 26 Nov 2021 (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.
Major depressive disorder is one of the most prevalent and disabling mental disorders worldwide. Forty percent of people with major depressive disorder are in moderate remission, with the remainder meeting the criteria for treatment-resistant depressive disorder (TRD), with an inadequate response to at least two different antidepressants of adequate dose and duration. Dysfunctionality in these individuals is frequent and severe and its importance contrasts with the absence of drugs to alleviate these deficits. Exercise programs, which were initially developed as interventions aimed at improving physical health in early stages or in mild symptomatology, have shown that they can also improve the symptoms of this disease in more advanced stages There is evidence of new therapeutic interventions for TRD. New pharmacological targets that aim to improve the evolution of depression and its functional repercussions augur that, in the future, new drugs will have to be combined with other therapeutic strategies, including exercise. Therefore, the objectives of this clinical trial with a control group are: 1) to analyze the changes in depressive symptoms in people diagnosed with TRD included in the exercise program compared to a control group; 2) to evaluate the improvement in physical health through cardiovascular risk factors and life expectancy suffered by this sector of the population, and 3) to analyze changes in functional status and quality of life. This is a prospective longitudinal intervention design (three months) in which people with TRD are included in two groups: 1) intervention with exercise (two days/week) and 2) control care with usual treatment. The aim is to find an improvement in mood and functionality with the implementation of exercise, as well as changes in physical areas such as blood pressure or body mass index, which are considered predictive factors of cardiovascular disease.
Detailed description
The presence of major depressive disorder (MDD) in today's society is worryingly high. Specifically, the prevalence-year prevalence of MDD in Spain is 3.9% and lifetime prevalence is 10.5%. The lifetime prevalence for men is 6.29% and 14.47% for women in Spain according to the ESEMED-Spain study. Although there is no explicit international consensus, the medical literature and research define treatment-resistant depression (TRD) as any MDD that does not respond to two trials of treatment antidepressant treatment at adequate doses and for an adequate duration of time.
MDD is the leading cause of years lived with disability worldwide, accounting for 11.9%. It has been estimated that during the year 2020 it could be second only to ischemic heart disease in disability-adjusted life years lost. Given this bleak scenario, different non-pharmacological strategies have been considered as possible complementary treatments to pharmacological treatment to help improve the prognosis of MDD and remission rates, such as exercise and electroconvulsive therapy.
Sedentary lifestyles are a very common feature in the severely mentally disordered population. One of the causes for this to occur is that people with MDD have very little confidence in their ability to exercise and lack the necessary social support. This inactivity together with other modifiable risk factors such as tobacco use, high blood pressure, and overweight/obesity, in addition to the side effects of pharmacological treatments contributes to the appearance of different diseases, as well as decreased life expectancy and quality of life. TRD can act as a cause or as a repercussion of physical inactivity.
It has been recognized for several years that the performance of regular exercise is cardioprotective, decreasing the incidence of cardiovascular diseases such as arterial hypertension, coronary artery disease, type 2 diabetes, and atherosclerosis. In addition to being cardioprotective, exercise has shown a positive association with psychological well-being and therapeutic benefits in older people with depressive disorder, depressive symptoms in patients with Alzheimer's disease and MDD.
Although there is still some controversy about the intensity and frequency of exercise, and the duration of the exercise program, the recommendations were the adoption of a moderate-intensity exercise program of at least 30 minutes on most days of the week, for 10-12 weeks. In the latest World Health Organization guidelines on physical activity (PA) and sedentary habits, for the improvement of quality of life in adults with TMD the general recommendations do not differ from the general population, i.e., people should accumulate throughout the week a minimum of 150-300 minutes of moderate aerobic PA or a minimum of 75-150 minutes of vigorous PA, or an equivalent combination of both in order to obtain notable health benefits. Also, in order to achieve additional health benefits, the participants should perform two days a week of moderate or higher intensity muscle-strengthening activities.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (care provider)
- Number of arms
- 2
- Model description
- Exercise group Atenttion Control
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Other: Combined trainingIntervention group: In the exercise session will carry out a combined training in four parts, low- intensity interval training in a bicycle, resistance circuit training, low- intensity interval training in a bicycle, and CORE exercises. |
| Attention Control | No intervention | –Regular in-hospital treatment with occupational activity sessions with the same frequency and duration as the intervention group. |
Who may qualify
- Ages
- 18 to 78 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Depression major disorder.
- 2 or more antdepressives resistant a treatment.
- Consent informed signed
Key exclusion criteria (7 listed)
- Schizophrenia or other disorders.
- Suicide risk.
- Unstable medic illness or unsuitable controlled.
- Disorder for use of active substances.
- Comorbidity with other psychiatric pathologies.
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 |
|---|---|---|
| Combined trainingLow-intensity interval training and resistance exercise | Other | Intervention group |
Primary outcome
Montgomery-Asberg Depressión Rating Scale (MADRS)
Time frame: 12 weeks
Ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders. Higher MADRS score indicates more severe depression, and each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Usual cutoff points are: 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression
Cardiorespiratory fitness
Time frame: 12 weeks
Cardiorespiratory fitness evaluation measured by cardiopulmonary exercise test. Maximu oxygen uptake measured in mL/kg/min or L/min is the gold standard variable.
3 secondary outcomes
Clinical Global Impression Scale (CGI)
Time frame: 12 weeks
Sheehan Disability Scale (SDS)
Time frame: 12 weeks
Treatment Satisfaction Questionnaire for Medication - 9 items (TSQM-9)
Time frame: 12 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
- Derived from this study: PubMed 41282982Tous-Espelosin M, Pavon-Navajas C, Etxaniz-Oses J, Canas-Garcia MT, Maldonado-Martin S, Orruno-Vivar J, Corres P, Iriarte-Yoller N. Effects of combined exercise training for adults with resistant major depression: a pilot study from the TRACE-RMD project. PeerJ. 2025 Nov 17;13:e20356. doi: 10.7717/peerj.20356. eCollection 2025.
- Derived from this study: PubMed 39696604Iriarte-Yoller N, Etxaniz-Oses J, Pavon-Navajas C, Tous-Espelosin M, Sanchez-Gomez PM, Maldonado-Martin S, Yoller-Elburgo AB, Elizagarate-Zabala E. Treatment with combined exercise in patients with resistant major depression (TRACE-RMD): study protocol for a randomised controlled trial. Trials. 2024 Dec 18;25(1):827. doi: 10.1186/s13063-024-08685-7.
- Individual participant dataSharing planned: Yes. A protocol paper will be written once the clinical trials identification number will be defined
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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.
NAGORE IRIARTE-YOLLER, MD principal investigator
PSYCHIATRIC HOSPITAL OF ÁLAVA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Combined training in people with Resistant Depression, Treatment, run by University of the Basque Country (UPV/EHU) at 1 site in Spain.
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 3 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 19 Dec 2023. 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 Spain. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sara Maldonado-Martin, PhD (34945013534, sara.maldonado@ehu.eus), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depressión Rating Scale (MADRS) (time frame: 12 weeks). The study lists 2 primary outcomes in all. 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 NCT05136027, which also lists 2 linked publications.
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 19 Dec 2023.