Treatment Resistant DepressionReModulaNCT05798143
Translational Biomarkers in Accelerated Neuromodulation for Treatment-resistant Depression
A study testing Accelerated Repetitive Transcranial Magnetic Stimulation in people with Treatment Resistant Depression, run by ITAB - Institute for Advanced Biomedical Technologies at 1 site in Italy.
Trial summary
Background: 30-50% of patients with Major Depressive Disorder (MDD) do not respond adequately despite two or more antidepressant treatments with proper dosage and timing of administration, configuring a condition of Treatment-Resistant Depression (TRD). Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Accelerated Repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteItaly
- Study dates
- 28 Feb 2023to 31 Dec 2028
- Phase
- Interventional
- 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
- Current diagnosis of Major Depressive Disorder (MDD), based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);
- Subjects without clinical response to at least two antidepressant treatments administered at adequate dosage and duration during the current episode;
- Stable psychopharmacological treatment for at least one month.
Who cannot join
- Co-morbidity with organic diseases that could interfere with magnetic stimulation safety (epilepsy, brain lesions or diseases, previous neurosurgery, metal grafts, cardiac devices) based on applied procedure guidelines;
- Diagnosis of Substance or Alcohol Use Disorder (DSM-5) in the past 6 months;
- Substances of abuse or alcohol acute intoxication or abstinence;
- Co-morbidity with significant organic or neurological diseases;
- Personal or familiar (1st degree relatives) medical history of seizures;
- Significant eye diseases that could interfere with ERG execution;
- For female patients: Pregnancy/breastfeeding.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
ITAB
Chieti, 66100
Mauro Pettorruso, MD, PhD, +393391979487, mauro.pettorruso@unich.it
About this study
Official title: Developing Translational Biomarkers to Predict Clinical Response in Treatment-resistant Depression: Towards a Personalized, Plasticity-enhancing Accelerated Neuromodulation
Background: 30-50% of patients with Major Depressive Disorder (MDD) do not respond adequately despite two or more antidepressant treatments with proper dosage and timing of administration, configuring a condition of Treatment-Resistant Depression (TRD). Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulation technique that uses a magnetic field to stimulate focal cortical brain regions and it has been approved by the FDA for the treatment of TRD. Accelerated rTMS (arTMS) protocols involve multiple daily sessions of rTMS and they have been shown to be equally effective and safe compared to rTMS protocols, with reduced administration time and potentially faster antidepressant efficacy.
Objectives: The main aim of this study is to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of rTMS to better characterize the clinical correlates of response in patients with TRD.
Read more
Eligibility: Subjects between 18 and 65 years suffering from TRD in stable psychopharmacological treatment for at least one month.
Design: This clinical trial includes three phases: 1) a screening phase; a rTMS continued treatment phase; and a follow-up.
In order to be enrolled, participants will be screened with:
- Medical history to assess the existence of the inclusion criteria and exclude any medical conditions that could contraindicate treatment with arTMS
- Questionnaires
After being enrolled, baseline data will be collected. In particular, participants will be administered:
- Questionnaires
- Functional MRI
- Cognitive tasks
- Eye examination with Electroretinography (ERG)
- Blood sampling
- Salivary cortisol sampling
Repetitive TMS will be delivered during 5 outpatient treatment days (4 times/die).
After treatment patients will be contacted by telephone on a weekly basis for the first 3 weeks, to carry out an assessment of the clinical condition.
A follow-up visit, in the clinic, will be carried out after 21 days from the last stimulation (Friday), with the administration of psychometric scales.
Blood samples will be taken on the first day of stimulation and the day after the last stimulation.
Salivary cortisol sampling will be taken before the start of the stimulation protocol, after the first stimulation day and immediately after the last stimulation session foreseen by the protocol.
fMRI will be performed during baseline and at the end of treatment. ERG will be performed before the start of the stimulation protocol, after the first stimulation and immediately after the last stimulation session foreseen by the protocol. Patients will undergo ERG again during the follow-up visit at 21 days.
Treatment includes:
- rTMS: A brief electrical current passes through the coil placed on the head. At each day, participants will receive four rTMS sessions (36 min), with a 55 min interval between sessions.
- MRIs: Patients will undergo two MRI sessions lasting 45 min. Blood pressure and respiratory rate will be recorded before the examination. During fMRI, patients will be asked to perform tasks.
- Eye examination with Electroretinography (ERG)
- Blood and salivary sampling.
- Screening tests and questionnaires.
Read the detailed description
The main aim of the study is to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of rTMS to consolidate the use of a cost-effective protocol and to better characterize the clinical correlates of response in patients with TRD. In addition, the present study proposes the following secondary objectives: A) identification of applicable and reliable peripheral biomarkers related to endophenotypes/biotypes, exportable in clinical practice to predict response to treatment; B) evaluation of potential synergistic, additive or antagonistic effects of MDD pharmacotherapies when used in combination with neuromodulation interventions.The study includes 3 psychiatric assessments with psychometric testing: T0 (enrollment), T1 (day 6), T2 (week 3, follow-up). At T0 (enrollment) the Researcher will fully inform the patient about the study, obtaining the patient's informed consent to participate in the study, and will determine the patient's eligibility. Patients will also undergo a battery of cognitive tasks aimed at measuring any changes caused by the neuromodulatory action of arTMS. During T1 (day 6), and T2 (3 weeks) the patient will again undergo the tests and neurocognitive evaluations. arTMS protocol involves 20 rTMS sessions (4/daily for 5 consecutive days, each session lasts 35 min with an interval of 55 min). Coil is placed on the left dorsolateral prefrontal cortex (LDLPFC), trains have a frequency of 10 Hz and a intensity of 120% of the individual resting motor threshold.
To investigate the possible effects of arTMS on brain connectivity, patients will undergo a functional neuroimaging study based on fMRI on T0 and T1. MDD biomarkers measurable by ERG could represent a valid aid in the personalization of treatments. ERG will be performed before the start of the stimulation protocol (T0), after the first stimulation and immediately after the last stimulation session foreseen by the protocol. Patients will undergo ERG again during the follow-up visit at 21 days (T2). Blood samples will be taken on the first day of stimulation (T0) and the day after the last stimulation to identify reliable peripheral biomarkers related to endophenotypes/biotypes, exportable in clinical practice to predict response to treatment. Salivary cortisol sampling will be taken before the start of the stimulation protocol (T0), after the first stimulation day and immediately after the last stimulation session foreseen by the protocol. Some variations in neuroendocrine biomarkers such as cortisol seem to be predictive of response to arTMS treatment. The analysis of the neuroimaging, ERG and peripheral data will lead to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of arTMS.
- Conditions
- Treatment Resistant Depression
- Being tested
- Accelerated Repetitive Transcranial Magnetic Stimulation
- Keywords
- Treatment resistant depression, accelerated repetitive transcranial magnetic stimulation, arTMS, TRD, biomarkers, neuroplasticity
- 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.
Accelerated Repetitive Transcranial Magnetic StimulationDevice
Also called arTMS
rTMS is a non-invasive brain stimulation technique. It will be used a MagPro R30 with the Cool-B-70 figure-of-eight coil (MagVenture, Falun, Denmark).
| Study group | Role | What they receive |
|---|---|---|
| Active arTMS treatment | Experimental | rTMS is a non-invasive brain stimulation technique. It will be used a MagPro R30 with the Cool-B-70 figure-of-eight coil (MagVenture, Falun, Denmark). Receives: Device: Accelerated Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in psychometric test indicator of depression - MADRS
Montgomery Asberg Depression rating scale (MADRS - 10 items - score 0-60) to measure relevance of mood, concentration, physical and sleep symptoms
Measured: Baseline; each 1 day of treatment ; at 1, 2, 3 and 4 weeks.
Changes in psychometric test indicator of depression - HAM-D 21
Hamilton Depression Scale (HAM-D - 21 items - score 0-69) to assess relevance and pervasiveness of depressive symptoms
Measured: Baseline; 1 week; 4 weeks
Changes in neuroplasticity - structural RM and fMRI (physiological parameter)
Functional MRI (which requires a preliminary structural MRI) produces images of the brain both in a "resting state" and when it is engaged in producing movements, sensations or when concentrated in activities involving emotional and cognitive responses. It is based on the ability to capture the signals emitted by hydrogen atoms when they are subjected to a magnetic field.
Measured: Baseline; day 6
Changes in neuroplasticity - DTI (physiological parameter)
Diffusion Tensor Imaging (DTI) techniques to assess the integrity of white matter tracts between brain regions. DTI data, accompanied by fMRI studies, in subjects with MDD are indicative of reduced functional connectivity between cortical and subcortical structures.
It is based on the principle of Brownian motion of water molecules, the signal is directly proportional to the integrity of the myelin sheath.
Measured: Baseline; day 6
Changes in responsivity of nervous tissue (physiological parameter)
ERG will be performed to gain an easy access to structural and functional nervous tissue alterations, usually observed in MDD patients and partially reversible with antidepressant treatment. The ERGs records the electrical activity following single light stimuli (flash), able to provide an indication of the activity of the external (cones, rods) and intermediate (amacrine, bipolar cells) layers of the retina
Measured: Baseline; 4 weeks
Rate of genetic polymorphism predictor of treatment response
Genetic tests investigating polymorphism (5-HT2A, 5-HT1A and BDNF receptors), possible predictors of antidepressant treatment response
Measured: Baseline; day 6
Change in BDNF level (physiological parameter)
BDNF levels will be evaluated by collecting a venous blood sample. BDNF is a member of the nerve growth factor (NGF) family of neurotrophic growth factors. Low levels of peripheral BDNF and NGF have been reported in mood disorders and other psychopathological conditions with normalization after antidepressant treatment or mood stabilization. The increase in serum levels of BDNF seems to reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by the suspension of alcohol intake and suggests that the synthesis of BDNF may have a role in the long-term maintenance of alcohol abstention. BDNF measurements will be calculated in pg/ml
Measured: Baseline; day 6
Change in pro-BDNF (physiological parameter)
Pro-BDNF is the precursor of BDNF and it acts as a repository of mature BDNF and acts itself by inducing neuronal thinning. Pro-BDNF levels will be evaluated by collecting a venous blood sample. Pro-BDNF measurements will be calculated in ng/ml.
Measured: Baseline; day 6
Changes in peripheral biomarkers - HPA axis (blood)
Hypothalamic-Pituitary-Adrenal axis will be evaluated assessing blood cortisol (mcg/dL) and ACTH (mcg/dL) levels
Measured: Baseline; day 6
Changes in peripheral biomarkers - HPT axis (FT3/FT4)
Hypothalamic-Pituitary-Thyroid aill be evaluated assessing, FT3 (pmol/L) and FT4 ( pmol/L) levels
Measured: Baseline; day 6
Changes in peripheral biomarkers - HPT axis (TSH)
Hypothalamic-Pituitary-Thyroid aill be evaluated assessing TSH (μIU/mL)
Measured: Baseline; day 6
Changes in peripheral biomarkers - HPA axis (saliva)
Hypothalamic-Pituitary-Adrenal axis will be evaluated assessing salivary (µL) levels of cortisol
Measured: Baseline; day 6
Changes in peripheral biomarkers - C reactive protein (physiological parameter)
C reactive protein, that indicates the inflammation degree, in mesured in mg/L.
Measured: Baseline; day 6
Secondary outcomes (18)
Cognitive Performance Using the THINC-it Tool
THINC-it (an acronym), include nclude the Spotter task (Choice Reaction Time), Symbol Check task(1-back test),Trails task(Trails Making Test B), and Codebreaker task (Digit Symbol Substitution Test).Z-value indicates the performance result (higher z higher performance)
Measured: Baseline, 4 weeks
Trait scales - TEMPS-A-brief Italian Version
Temperament Evaluation of Memphis, Pisa and San Diego Autoquestionnaire brief version (TEMPS-A-brief Italian Version - subscales' score: cyclothymic 0-12; depressive 0-8; irritable 0-8; hyperthymic: 0-8; anxious 0-3): a 39 items scale to investigate temperamental traits
Measured: Baseline
Trait scales - BIS-11
Barratt Impulsiveness Scale, Version 11 (BIS-11, 30 item - score 30-120) to evaluate temperamental impulsive traits. BIS-11 consists in 3 subscale: "Attentional Impulsivity", "Motor Impulsivity" and "Nonplanning Impulsivity"
Measured: Baseline
Trait scales - CTQ-28 items
Childhood Trauma Questionnaire (CTQ-28 items - score 0-112) to evaluate childhood and adolescence abuses and trauma
Measured: Baseline
Trait scales - TAS-20
Toronto Alexithymia Scale (TAS-20 - 20 items - score 20-100) to assess emotional self-awareness
Measured: Baseline
Trait scales - BFQ-R
Big Five Questionnaire (BFQ-R 60 items - score 60-300) to assess the big five personality traits (extraversion, agreeableness, conscientiousness, neuroticism, and openness)
Measured: Baseline
State scales - ASMR
Altman Self-Rating Mania Scale (ASRM - 5 item - score 0-20) to evaluate presence and relevance of manic symptoms
Measured: Day 1,2,3,4,5
State scales - TMS collateral effect scale
TMS collateral effect scale, to evaluate possible collaterality due to magnetic stimulation
Measured: After each TMS session
State scales - YMRS
Young Mania Rating Scale (YMRS - 11 item - score 0-44) investigating symptoms of mania
Measured: Baseline; 1 week; 4 weeks
State scales - BPRS
Brief Psychiatric Rating Scale (BPRS - 24 items - score 24-168) for a global psychopathological assessment
Measured: Baseline; 1 week; 4 weeks
State scales - SHAPS
Snaith-Hamilton Pleasure Scale (SHAPS - 14 items - score 0-42) to estimate hedonic tone
Measured: Baseline; 1 week; 4 weeks
State scales - BHS
Beck Hopelessness Scale (BHS- 20 items - score 0-20) to evaluate negative attitudes towards the future and pessimism
Measured: Baseline; 1 week; 4 weeks
State scales - ISI
Insomnia Severity Index (ISI - 5 items - score 0-28) to assess quality of sleep
Measured: Baseline; 1 week; 4 weeks
State scales - SDS
Sheehan Disability Scale (SDS 5 items - score 0-30) to measure disability perceived by patient
Measured: Baseline; 1 week; 4 weeks
State scales - CGI-S
Clinical Global Impression - Severity scale (CGI-S - score 1-7) to estimate clinical disease entity
Measured: Baseline; 1 week; 4 weeks
State scales - LAPS
Leuven affect and pleasure scale (LAPS 16 items - score 0-160) to assess positive and negative affective and hedonic tone
Measured: Baseline; 1 week; 4 weeks
State scales - SF
Health Questionnaire (SF-12 items - score 12-47) to evaluate quality of life
Measured: Baseline; 1 week; 4 weeks
Changes in psychometric test indicator of depression - HAM-A 21
Hamilton Anxiety Scale (HAM-A - 21 items) to assess anxiety relevance
Measured: Baseline; 1 week; 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2023
- Study start28 Feb 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ITAB - Institute for Advanced Biomedical Technologies
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mauro Pettorruso, ITAB - Institute for Advanced Biomedical Technologies
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05798143
- Sponsor's protocol ID
- remodula
- Acronym
- ReModula
- Status last verified
- Mar 2023
- First submitted
- 3 Mar 2023
- Last updated
- 4 Apr 2023
- 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 4 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing Translational Biomarkers to Predict Clinical Response in Treatment-resistant Depression: Towards a Personalized, Plasticity-enhancing Accelerated Neuromodulation
- ClinicalTrials.gov ID
- NCT05798143
- Acronym / sponsor ID
- ReModula / remodula
- Conditions
- Treatment Resistant Depression
- Keywords
- Treatment resistant depression, accelerated repetitive transcranial magnetic stimulation, arTMS, TRD, biomarkers, neuroplasticity
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- ITAB - Institute for Advanced Biomedical TechnologiesUniversity, hospital or other
- Study start
- 28 Feb 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 4 Apr 2023 (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.
Background: 30-50% of patients with Major Depressive Disorder (MDD) do not respond adequately despite two or more antidepressant treatments with proper dosage and timing of administration, configuring a condition of Treatment-Resistant Depression (TRD). Repetitive Transcranial Magnetic Stimulation (rTMS) is a neuromodulation technique that uses a magnetic field to stimulate focal cortical brain regions and it has been approved by the FDA for the treatment of TRD. Accelerated rTMS (arTMS) protocols involve multiple daily sessions of rTMS and they have been shown to be equally effective and safe compared to rTMS protocols, with reduced administration time and potentially faster antidepressant efficacy.
Objectives: The main aim of this study is to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of rTMS to better characterize the clinical correlates of response in patients with TRD.
Eligibility: Subjects between 18 and 65 years suffering from TRD in stable psychopharmacological treatment for at least one month.
Design: This clinical trial includes three phases: 1) a screening phase; a rTMS continued treatment phase; and a follow-up.
In order to be enrolled, participants will be screened with:
- Medical history to assess the existence of the inclusion criteria and exclude any medical conditions that could contraindicate treatment with arTMS
- Questionnaires
After being enrolled, baseline data will be collected. In particular, participants will be administered:
- Questionnaires
- Functional MRI
- Cognitive tasks
- Eye examination with Electroretinography (ERG)
- Blood sampling
- Salivary cortisol sampling
Repetitive TMS will be delivered during 5 outpatient treatment days (4 times/die).
After treatment patients will be contacted by telephone on a weekly basis for the first 3 weeks, to carry out an assessment of the clinical condition.
A follow-up visit, in the clinic, will be carried out after 21 days from the last stimulation (Friday), with the administration of psychometric scales.
Blood samples will be taken on the first day of stimulation and the day after the last stimulation.
Salivary cortisol sampling will be taken before the start of the stimulation protocol, after the first stimulation day and immediately after the last stimulation session foreseen by the protocol.
fMRI will be performed during baseline and at the end of treatment. ERG will be performed before the start of the stimulation protocol, after the first stimulation and immediately after the last stimulation session foreseen by the protocol. Patients will undergo ERG again during the follow-up visit at 21 days.
Treatment includes:
- rTMS: A brief electrical current passes through the coil placed on the head. At each day, participants will receive four rTMS sessions (36 min), with a 55 min interval between sessions.
- MRIs: Patients will undergo two MRI sessions lasting 45 min. Blood pressure and respiratory rate will be recorded before the examination. During fMRI, patients will be asked to perform tasks.
- Eye examination with Electroretinography (ERG)
- Blood and salivary sampling.
- Screening tests and questionnaires.
Detailed description
The main aim of the study is to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of rTMS to consolidate the use of a cost-effective protocol and to better characterize the clinical correlates of response in patients with TRD. In addition, the present study proposes the following secondary objectives: A) identification of applicable and reliable peripheral biomarkers related to endophenotypes/biotypes, exportable in clinical practice to predict response to treatment; B) evaluation of potential synergistic, additive or antagonistic effects of MDD pharmacotherapies when used in combination with neuromodulation interventions.The study includes 3 psychiatric assessments with psychometric testing: T0 (enrollment), T1 (day 6), T2 (week 3, follow-up). At T0 (enrollment) the Researcher will fully inform the patient about the study, obtaining the patient's informed consent to participate in the study, and will determine the patient's eligibility. Patients will also undergo a battery of cognitive tasks aimed at measuring any changes caused by the neuromodulatory action of arTMS. During T1 (day 6), and T2 (3 weeks) the patient will again undergo the tests and neurocognitive evaluations. arTMS protocol involves 20 rTMS sessions (4/daily for 5 consecutive days, each session lasts 35 min with an interval of 55 min). Coil is placed on the left dorsolateral prefrontal cortex (LDLPFC), trains have a frequency of 10 Hz and a intensity of 120% of the individual resting motor threshold.
To investigate the possible effects of arTMS on brain connectivity, patients will undergo a functional neuroimaging study based on fMRI on T0 and T1. MDD biomarkers measurable by ERG could represent a valid aid in the personalization of treatments. ERG will be performed before the start of the stimulation protocol (T0), after the first stimulation and immediately after the last stimulation session foreseen by the protocol. Patients will undergo ERG again during the follow-up visit at 21 days (T2). Blood samples will be taken on the first day of stimulation (T0) and the day after the last stimulation to identify reliable peripheral biomarkers related to endophenotypes/biotypes, exportable in clinical practice to predict response to treatment. Salivary cortisol sampling will be taken before the start of the stimulation protocol (T0), after the first stimulation day and immediately after the last stimulation session foreseen by the protocol. Some variations in neuroendocrine biomarkers such as cortisol seem to be predictive of response to arTMS treatment. The analysis of the neuroimaging, ERG and peripheral data will lead to identify MDD endophenotypes/biotypes predictive of response to accelerated treatment of arTMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Active arTMS treatment | Experimental | Device: Accelerated Repetitive Transcranial Magnetic StimulationrTMS is a non-invasive brain stimulation technique. It will be used a MagPro R30 with the Cool-B-70 figure-of-eight coil (MagVenture, Falun, Denmark). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Current diagnosis of Major Depressive Disorder (MDD), based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);
- Subjects without clinical response to at least two antidepressant treatments administered at adequate dosage and duration during the current episode;
- Stable psychopharmacological treatment for at least one month.
Key exclusion criteria (7 listed)
- Co-morbidity with organic diseases that could interfere with magnetic stimulation safety (epilepsy, brain lesions or diseases, previous neurosurgery, metal grafts, cardiac devices) based on applied procedure guidelines;
- Diagnosis of Substance or Alcohol Use Disorder (DSM-5) in the past 6 months;
- Substances of abuse or alcohol acute intoxication or abstinence;
- Co-morbidity with significant organic or neurological diseases;
- Personal or familiar (1st degree relatives) medical history of seizures;
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 |
|---|---|---|
| Accelerated Repetitive Transcranial Magnetic StimulationAlso: arTMSrTMS is a non-invasive brain stimulation technique. It will be used a MagPro R30 with the Cool-B-70 figure-of-eight coil (MagVenture, Falun, Denmark). | Device | Active arTMS treatment |
Primary outcome
Changes in psychometric test indicator of depression - MADRS
Time frame: Baseline; each 1 day of treatment ; at 1, 2, 3 and 4 weeks.
Montgomery Asberg Depression rating scale (MADRS - 10 items - score 0-60) to measure relevance of mood, concentration, physical and sleep symptoms
Changes in psychometric test indicator of depression - HAM-D 21
Time frame: Baseline; 1 week; 4 weeks
Hamilton Depression Scale (HAM-D - 21 items - score 0-69) to assess relevance and pervasiveness of depressive symptoms
Changes in neuroplasticity - structural RM and fMRI (physiological parameter)
Time frame: Baseline; day 6
Functional MRI (which requires a preliminary structural MRI) produces images of the brain both in a "resting state" and when it is engaged in producing movements, sensations or when concentrated in activities involving emotional and cognitive responses. It is based on the ability to capture the signals emitted by hydrogen atoms when they are subjected to a magnetic field.
Changes in neuroplasticity - DTI (physiological parameter)
Time frame: Baseline; day 6
Diffusion Tensor Imaging (DTI) techniques to assess the integrity of white matter tracts between brain regions. DTI data, accompanied by fMRI studies, in subjects with MDD are indicative of reduced functional connectivity between cortical and subcortical structures. It is based on the principle of Brownian motion of water molecules, the signal is directly proportional to the integrity of the myelin sheath.
Changes in responsivity of nervous tissue (physiological parameter)
Time frame: Baseline; 4 weeks
ERG will be performed to gain an easy access to structural and functional nervous tissue alterations, usually observed in MDD patients and partially reversible with antidepressant treatment. The ERGs records the electrical activity following single light stimuli (flash), able to provide an indication of the activity of the external (cones, rods) and intermediate (amacrine, bipolar cells) layers of the retina
Rate of genetic polymorphism predictor of treatment response
Time frame: Baseline; day 6
Genetic tests investigating polymorphism (5-HT2A, 5-HT1A and BDNF receptors), possible predictors of antidepressant treatment response
Change in BDNF level (physiological parameter)
Time frame: Baseline; day 6
BDNF levels will be evaluated by collecting a venous blood sample. BDNF is a member of the nerve growth factor (NGF) family of neurotrophic growth factors. Low levels of peripheral BDNF and NGF have been reported in mood disorders and other psychopathological conditions with normalization after antidepressant treatment or mood stabilization. The increase in serum levels of BDNF seems to reflect the concomitant activation of BDNF synthesis that accompanies the neuronal remodeling triggered by the suspension of alcohol intake and suggests that the synthesis of BDNF may have a role in the long-term maintenance of alcohol abstention. BDNF measurements will be calculated in pg/ml
Change in pro-BDNF (physiological parameter)
Time frame: Baseline; day 6
Pro-BDNF is the precursor of BDNF and it acts as a repository of mature BDNF and acts itself by inducing neuronal thinning. Pro-BDNF levels will be evaluated by collecting a venous blood sample. Pro-BDNF measurements will be calculated in ng/ml.
Changes in peripheral biomarkers - HPA axis (blood)
Time frame: Baseline; day 6
Hypothalamic-Pituitary-Adrenal axis will be evaluated assessing blood cortisol (mcg/dL) and ACTH (mcg/dL) levels
Changes in peripheral biomarkers - HPT axis (FT3/FT4)
Time frame: Baseline; day 6
Hypothalamic-Pituitary-Thyroid aill be evaluated assessing, FT3 (pmol/L) and FT4 ( pmol/L) levels
Changes in peripheral biomarkers - HPT axis (TSH)
Time frame: Baseline; day 6
Hypothalamic-Pituitary-Thyroid aill be evaluated assessing TSH (μIU/mL)
Changes in peripheral biomarkers - HPA axis (saliva)
Time frame: Baseline; day 6
Hypothalamic-Pituitary-Adrenal axis will be evaluated assessing salivary (µL) levels of cortisol
Changes in peripheral biomarkers - C reactive protein (physiological parameter)
Time frame: Baseline; day 6
C reactive protein, that indicates the inflammation degree, in mesured in mg/L.
18 secondary outcomes
Cognitive Performance Using the THINC-it Tool
Time frame: Baseline, 4 weeks
Trait scales - TEMPS-A-brief Italian Version
Time frame: Baseline
Trait scales - BIS-11
Time frame: Baseline
Trait scales - CTQ-28 items
Time frame: Baseline
Trait scales - TAS-20
Time frame: Baseline
Trait scales - BFQ-R
Time frame: Baseline
State scales - ASMR
Time frame: Day 1,2,3,4,5
State scales - TMS collateral effect scale
Time frame: After each TMS session
State scales - YMRS
Time frame: Baseline; 1 week; 4 weeks
State scales - BPRS
Time frame: Baseline; 1 week; 4 weeks
State scales - SHAPS
Time frame: Baseline; 1 week; 4 weeks
State scales - BHS
Time frame: Baseline; 1 week; 4 weeks
State scales - ISI
Time frame: Baseline; 1 week; 4 weeks
State scales - SDS
Time frame: Baseline; 1 week; 4 weeks
State scales - CGI-S
Time frame: Baseline; 1 week; 4 weeks
State scales - LAPS
Time frame: Baseline; 1 week; 4 weeks
State scales - SF
Time frame: Baseline; 1 week; 4 weeks
Changes in psychometric test indicator of depression - HAM-A 21
Time frame: Baseline; 1 week; 4 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 4 Apr 2023.
- Individual participant dataSharing planned: No
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ALTO-207 in Adults With Treatment-resistant Depression (TRD)
Treatment-resistant Depression (TRD)
RecruitingPhase 3
Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression
Major Depression
RecruitingPhase 3
InTRavenous kEtAmine and immerSive virtUal Reality to Treat dEpression
Treatment Resistant Depression
Recruiting
Effects of Transcranial Direct Current Stimulation (tDCS) in the Management of Suicidal Ideation
Depression and Suicide
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Accelerated Repetitive Transcranial Magnetic Stimulation in people with Treatment Resistant Depression, run by ITAB - Institute for Advanced Biomedical Technologies at 1 site in Italy.
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: looking for participants now, as of the sponsor's last update on 4 Apr 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 Italy. 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?
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 Mauro Pettorruso, MD, PhD (+393391979487, mauro.pettorruso@unich.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in psychometric test indicator of depression - MADRS (time frame: Baseline; each 1 day of treatment ; at 1, 2, 3 and 4 weeks.). The study lists 13 primary outcomes in all. 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 4 Apr 2023.