Ignite Creation Date:
2024-05-06 @ 2:10 PM
Last Modification Date:
2024-10-26 @ 1:26 PM
Study NCT ID:
NCT04239651
Status:
COMPLETED
Last Update Posted:
2022-08-02
First Post:
2019-12-05
Brief Title:
rTMS With and Without iCBT For the Treatment of Resistant Depression TRD
Sponsor:
University of Alberta
Organization:
University of Alberta
Study Overview
Official Title:
Repetitive Transcranial Magnetic Stimulation rTMS With and Without Internet-Delivered Cognitive Behavior Therapy iCBT For the Treatment of Resistant Depression TRD Protocol for Patient - Centered Randomized Controlled Pilot Trial
Status:
COMPLETED
Status Verified Date:
2022-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This is a prospective two-arm randomized controlled trial 100 patients diagnosed with resistant depression in psychiatric care clinic in Edmonton Alberta Canada will be randomized to one of two conditions 1 enrolment in rTMS sessions alone 2 enrolment in the rTMS sessions plus iCBT Patients in each group will complete evaluation measures eg recovery general symptomatology and functional outcomes at baseline 1 month 3 months and 6 months The primary outcome measure would be changes to scores on the Hamilton Depression Rating Scale Patient service utilization data and clinician-rated measures will also be used to gauge patient progress Patient data will be analyzed with descriptive statistics repeated measures and correlational analyses
Detailed Description:
BACKGROUND AND RATIONALE
Major depression is a severe disabling and potentially lethal clinical disorder While there are a wide variety of pharmaceutical agents available as treatments for major depression only about half of patients respond to an initial course of antidepressant pharmacotherapy It has been conservatively estimated that at least 15 of all patients with major depressive disorder remain refractory to any treatment intervention While a complex relationship exists between disease chronicity and ineffective treatment clinical evidence suggests that the greater the number of treatment failures the less likelihood of a good treatment response to subsequent interventions The reported results of the STARD study are the most vivid example of this clinical phenomenon In that work there was a progressive likelihood of poorer response with each successive treatment failure For example after the first treatment attempt about 30 of patients remitted By the time that a patient had experienced definitive treatment failures the likelihood of achieving remission with the fourth treatment option offered fell below 10 Taken together these facts underline the clinical urgency for physicians to identify treatment resistant patients as early as possible so that alternative treatments with proven efficacies may be offered sooner In turn this will result in superior treatment outcomes for these treatment resistant patients
Technology and the Internet have dramatically changed medicine According to Statistics Canada 83 of Canadians had Internet access in 2012 and more than 70 use the Internet daily 62 were smartphone users E-Mental health refers to the use of computers Internet and mobile devices for mental health information and care E-Mental health applications are now widely available for information screening assessment and monitoring interactive self-management psychotherapy and social support Clinicians should be aware that there are benefits and potential harms to using and recommending e-Mental health applications and that few have good-quality evidence to support effectiveness Meta-analyses and reviews of computer-based psychological treatment for the treatment of MDD whether delivered over the Internet or as a stand-alone program demonstrate convincing support for these treatment modalities Internet- and computer-delivered cognitive behaviour therapy iCBT can also be helpful in relapse prevention
In 2009 the Canadian Network for Mood and Anxiety Treatments CANMAT a not-for-profit scientific and educational organization published a revision of evidence-based clinical guidelines for the treatment of depressive disorders CANMAT has updated these guidelines in 2016 to reflect new evidence in the field Neurostimulation or neuromodulation is an expanding area of research and clinical interest driven in part by the increasing knowledge base on the neurocircuitry of depression Most of these neurostimulation treatments have been studied and are used in patients with TRD who have failed to respond to standard treatments However there is no previous study which has examined the effect of rTMS plus iCBT in comparison to rTMS alone
Repetitive Transcranial Magnetic Stimulation rTMS
rTMS uses powerful 10-25 Tesla focused magnetic field pulses to induce electrical currents in neural tissue noninvasively via an inductor coil placed against the scalp Therapeutic rTMS is usually delivered by a trained technician or nurse under physician supervision Unlike Electroconvulsive Therapy ECT no anesthesia is required The therapeutic mechanism of rTMS is still under investigation with mechanisms proposed at both cell-molecular and network levels Repeated rTMS sessions can exert therapeutic effects lasting several months Clinical trials and naturalistic studies have found maximal effects at 26 to 28 sessions Clinical experience concurs in suggesting 20 sessions before declaring treatment failure with extension to 25 to 30 sessions if improvements occur
More than 30 systematic reviews and meta-analyses have been conducted on rTMS in depression with most studies involving patients with some degree of treatment resistance ie having failed at least 1 or 2 antidepressant trials Overall rTMS is considered a first-line treatment for MDD for patients who have failed at least 1 antidepressant treatment
Cognitive behavioral therapy CBT Psychotherapy
Cognitive behavioral therapy CBT is an evidence-based structured intensive time-limited symptom-focused form of psychotherapy recommended for the treatment of major depression and anxiety disorders Internet-delivered CBT iCBT is structured CBT delivered via the internet Cognitive behavioral therapy helps people become aware of how certain negative automatic thoughts attitudes expectations and beliefs contribute to feelings of sadness and anxiety People undergoing CBT learn how their thinking patterns which may have developed in the past to deal with difficult or painful experiences can be identified and changed to reduce unhappiness
Barriers to face-to-face conventional ways for treatment include stigmas around people seeking help in person geography distance from health care professional time and cost Increasingly there is a desire to pursue internet delivery as an option to increase access to treatment
Internet-delivered CBT iCBT consists of structured modules with clearly defined goals and is delivered via the internet Although there are many types of iCBT programs each are goal-oriented sessions that typically consist of 8 to 12 modules and can be guided or unguided Internet-delivered CBT programs are made available by computer smartphone or tablet for a fee With unguided iCBT patients are informed of a website through which they can participate in an online self-directed program Guided iCBT involves support from a regulated health professional eg social worker psychologist psychotherapist occupational therapist nurse or physician In guided iCBT people complete modules and communicate via email text messages or telephone calls their progress to a regulated health professional
OBJECTIVES A goal of the project is to evaluate the feasibility of implementing rTMS plus iCBT for treatment of patients diagnosed with TRD Another goal of the project is to assess the initial comparative clinical effectiveness of rTMS treatments when used with and without iCBT
Because of the limited availability of data in this specific area another goal of the study is to generate effect size data for these interventions which will help in sample size and power calculations for a full randomized clinical trial The patients outcomes are organized according to recovery variables eg recovery and stigma functional variables quality of life and employment symptom variables psychological symptoms and general outcomes and other outcomes will be service variables eg heath service utilization cost and satisfaction
METHODS
This study will be a prospective parallel design two-arm rater-blinded Randomized Controlled Trial RCT with a recruitment period of 12 months and applying active treatment for 6 weeks and an observation period of 6 months for each participant The research will be carried out in an Addiction and Mental Health clinic in a large socio-demographically diverse city in Western Canada Edmonton Alberta
INTERVENTIONS Patients would be randomly assigned to receive either rTMS alone or rTMSplus iCBT Patients in both arms of the study will be assigned to an introductory visit to introduce the rTMS system to them and explain the procedure which will be carried out in each visit All patients will be scheduled to receive 30 sessions of rTMS treatments over a six-week period as pre-determined by Alberta Health Services Strategic Clinical Network for Addiction and Mental Health In addition patients in the rTMS plus iCBT arm of the study would be assisted to register on the iCBT program MoodGym to receive unique login information To reduce in-person contact due to COVID-19 protocols patients would be remotely assisted via phone to participate in 12 one-hour sessions of iCBT at the clinic prior to receiving rTMS treatments These iCBT sessions would be scheduled in about three days intervals ideally Tuesdays and Thursdays so that patients receive two iCBT sessions each week Patients would also be encouraged to continue with iCBT treatments beyond the scheduled sessions
All patients will be followed up for 6 months and would be encouraged to continue to receive whatever community clinic program treatments or supports are part of their usual care
HYPOTHESIS The investigators hypothesize that patients enrolled in the rTMS plus iCBT treatment arm of the study will achieve superior outcomes compared with patients enrolled in the rTMS alone arm of the study on each outcome measure used
SAMPLE SIZE The study will therefore be limited to a sample size of 100 with about 50 patients recruited into each arm of the study Patients transitioning from resistance of the pharmacological treatment are vulnerable to severe depressive attacks and it can reasonably be expected that only a small number of eligible participants will enroll in and complete the study
RANDOMIZATION AND BLINDING Randomization will be stratified by using permuted blocks to ensure balance 11 between the two follow-up treatment groups The randomization codes will be transmitted by an independent statistician via text message directly to a researchers password-protected phone line with a secure online backup This will commence as soon as participants sign the consent forms
Because it will not be possible for participants to be blinded treatment allocation will be made explicit to them as soon as randomization is concluded Primary outcome assessors will be blinded to treatment group allocation by not involving them in discussions about study participants and not granting them access to the database which contains the randomization code After data collection is complete all data will undergo a blind review for the purposes of finalizing the planned analysis
FOLLOW-UP ASSESSMENT At 1 3 and 6 months a blinded researcher will contact all study participants and assist them to complete a range of assessment tools relating to the primary and secondary outcome measures They will be offered the opportunity to complete the assessments face to face or over the phone At 6 months data related to each persons clinic programme attendance rates and utilization of health services will be compiled from administrative records by the blinded researcher
PATIENT AND PUBLIC INVOLVEMENT This study was designed to address the clinical urgency to identify and respond to early evidence of treatment resistance using treatments that have proven efficacy in these more difficult-to-treat psychiatric patients The study is designed as patient-oriented research with the active involvement of a patient representative who will be a coauthor of the study protocol The randomized trial offers patients the opportunity to provide feedback regarding the burden of the intervention through a focused group workshop involving a cross section of patients in the two arms of the study
ETHICS AND DISSEMINATION The study will be conducted in accordance with the Declaration of Helsinki Hong Kong Amendment and Good Clinical Practice Canadian Guidelines Written informed consent will be obtained from each participant The study results expected 18 months after commencement of recruitment will be disseminated at several levels including patients practitioners academicsresearchers and healthcare organizations
Major depression is a severe disabling and potentially lethal clinical disorder While there are a wide variety of pharmaceutical agents available as treatments for major depression only about half of patients respond to an initial course of antidepressant pharmacotherapy It has been conservatively estimated that at least 15 of all patients with major depressive disorder remain refractory to any treatment intervention While a complex relationship exists between disease chronicity and ineffective treatment clinical evidence suggests that the greater the number of treatment failures the less likelihood of a good treatment response to subsequent interventions The reported results of the STARD study are the most vivid example of this clinical phenomenon In that work there was a progressive likelihood of poorer response with each successive treatment failure For example after the first treatment attempt about 30 of patients remitted By the time that a patient had experienced definitive treatment failures the likelihood of achieving remission with the fourth treatment option offered fell below 10 Taken together these facts underline the clinical urgency for physicians to identify treatment resistant patients as early as possible so that alternative treatments with proven efficacies may be offered sooner In turn this will result in superior treatment outcomes for these treatment resistant patients
Technology and the Internet have dramatically changed medicine According to Statistics Canada 83 of Canadians had Internet access in 2012 and more than 70 use the Internet daily 62 were smartphone users E-Mental health refers to the use of computers Internet and mobile devices for mental health information and care E-Mental health applications are now widely available for information screening assessment and monitoring interactive self-management psychotherapy and social support Clinicians should be aware that there are benefits and potential harms to using and recommending e-Mental health applications and that few have good-quality evidence to support effectiveness Meta-analyses and reviews of computer-based psychological treatment for the treatment of MDD whether delivered over the Internet or as a stand-alone program demonstrate convincing support for these treatment modalities Internet- and computer-delivered cognitive behaviour therapy iCBT can also be helpful in relapse prevention
In 2009 the Canadian Network for Mood and Anxiety Treatments CANMAT a not-for-profit scientific and educational organization published a revision of evidence-based clinical guidelines for the treatment of depressive disorders CANMAT has updated these guidelines in 2016 to reflect new evidence in the field Neurostimulation or neuromodulation is an expanding area of research and clinical interest driven in part by the increasing knowledge base on the neurocircuitry of depression Most of these neurostimulation treatments have been studied and are used in patients with TRD who have failed to respond to standard treatments However there is no previous study which has examined the effect of rTMS plus iCBT in comparison to rTMS alone
Repetitive Transcranial Magnetic Stimulation rTMS
rTMS uses powerful 10-25 Tesla focused magnetic field pulses to induce electrical currents in neural tissue noninvasively via an inductor coil placed against the scalp Therapeutic rTMS is usually delivered by a trained technician or nurse under physician supervision Unlike Electroconvulsive Therapy ECT no anesthesia is required The therapeutic mechanism of rTMS is still under investigation with mechanisms proposed at both cell-molecular and network levels Repeated rTMS sessions can exert therapeutic effects lasting several months Clinical trials and naturalistic studies have found maximal effects at 26 to 28 sessions Clinical experience concurs in suggesting 20 sessions before declaring treatment failure with extension to 25 to 30 sessions if improvements occur
More than 30 systematic reviews and meta-analyses have been conducted on rTMS in depression with most studies involving patients with some degree of treatment resistance ie having failed at least 1 or 2 antidepressant trials Overall rTMS is considered a first-line treatment for MDD for patients who have failed at least 1 antidepressant treatment
Cognitive behavioral therapy CBT Psychotherapy
Cognitive behavioral therapy CBT is an evidence-based structured intensive time-limited symptom-focused form of psychotherapy recommended for the treatment of major depression and anxiety disorders Internet-delivered CBT iCBT is structured CBT delivered via the internet Cognitive behavioral therapy helps people become aware of how certain negative automatic thoughts attitudes expectations and beliefs contribute to feelings of sadness and anxiety People undergoing CBT learn how their thinking patterns which may have developed in the past to deal with difficult or painful experiences can be identified and changed to reduce unhappiness
Barriers to face-to-face conventional ways for treatment include stigmas around people seeking help in person geography distance from health care professional time and cost Increasingly there is a desire to pursue internet delivery as an option to increase access to treatment
Internet-delivered CBT iCBT consists of structured modules with clearly defined goals and is delivered via the internet Although there are many types of iCBT programs each are goal-oriented sessions that typically consist of 8 to 12 modules and can be guided or unguided Internet-delivered CBT programs are made available by computer smartphone or tablet for a fee With unguided iCBT patients are informed of a website through which they can participate in an online self-directed program Guided iCBT involves support from a regulated health professional eg social worker psychologist psychotherapist occupational therapist nurse or physician In guided iCBT people complete modules and communicate via email text messages or telephone calls their progress to a regulated health professional
OBJECTIVES A goal of the project is to evaluate the feasibility of implementing rTMS plus iCBT for treatment of patients diagnosed with TRD Another goal of the project is to assess the initial comparative clinical effectiveness of rTMS treatments when used with and without iCBT
Because of the limited availability of data in this specific area another goal of the study is to generate effect size data for these interventions which will help in sample size and power calculations for a full randomized clinical trial The patients outcomes are organized according to recovery variables eg recovery and stigma functional variables quality of life and employment symptom variables psychological symptoms and general outcomes and other outcomes will be service variables eg heath service utilization cost and satisfaction
METHODS
This study will be a prospective parallel design two-arm rater-blinded Randomized Controlled Trial RCT with a recruitment period of 12 months and applying active treatment for 6 weeks and an observation period of 6 months for each participant The research will be carried out in an Addiction and Mental Health clinic in a large socio-demographically diverse city in Western Canada Edmonton Alberta
INTERVENTIONS Patients would be randomly assigned to receive either rTMS alone or rTMSplus iCBT Patients in both arms of the study will be assigned to an introductory visit to introduce the rTMS system to them and explain the procedure which will be carried out in each visit All patients will be scheduled to receive 30 sessions of rTMS treatments over a six-week period as pre-determined by Alberta Health Services Strategic Clinical Network for Addiction and Mental Health In addition patients in the rTMS plus iCBT arm of the study would be assisted to register on the iCBT program MoodGym to receive unique login information To reduce in-person contact due to COVID-19 protocols patients would be remotely assisted via phone to participate in 12 one-hour sessions of iCBT at the clinic prior to receiving rTMS treatments These iCBT sessions would be scheduled in about three days intervals ideally Tuesdays and Thursdays so that patients receive two iCBT sessions each week Patients would also be encouraged to continue with iCBT treatments beyond the scheduled sessions
All patients will be followed up for 6 months and would be encouraged to continue to receive whatever community clinic program treatments or supports are part of their usual care
HYPOTHESIS The investigators hypothesize that patients enrolled in the rTMS plus iCBT treatment arm of the study will achieve superior outcomes compared with patients enrolled in the rTMS alone arm of the study on each outcome measure used
SAMPLE SIZE The study will therefore be limited to a sample size of 100 with about 50 patients recruited into each arm of the study Patients transitioning from resistance of the pharmacological treatment are vulnerable to severe depressive attacks and it can reasonably be expected that only a small number of eligible participants will enroll in and complete the study
RANDOMIZATION AND BLINDING Randomization will be stratified by using permuted blocks to ensure balance 11 between the two follow-up treatment groups The randomization codes will be transmitted by an independent statistician via text message directly to a researchers password-protected phone line with a secure online backup This will commence as soon as participants sign the consent forms
Because it will not be possible for participants to be blinded treatment allocation will be made explicit to them as soon as randomization is concluded Primary outcome assessors will be blinded to treatment group allocation by not involving them in discussions about study participants and not granting them access to the database which contains the randomization code After data collection is complete all data will undergo a blind review for the purposes of finalizing the planned analysis
FOLLOW-UP ASSESSMENT At 1 3 and 6 months a blinded researcher will contact all study participants and assist them to complete a range of assessment tools relating to the primary and secondary outcome measures They will be offered the opportunity to complete the assessments face to face or over the phone At 6 months data related to each persons clinic programme attendance rates and utilization of health services will be compiled from administrative records by the blinded researcher
PATIENT AND PUBLIC INVOLVEMENT This study was designed to address the clinical urgency to identify and respond to early evidence of treatment resistance using treatments that have proven efficacy in these more difficult-to-treat psychiatric patients The study is designed as patient-oriented research with the active involvement of a patient representative who will be a coauthor of the study protocol The randomized trial offers patients the opportunity to provide feedback regarding the burden of the intervention through a focused group workshop involving a cross section of patients in the two arms of the study
ETHICS AND DISSEMINATION The study will be conducted in accordance with the Declaration of Helsinki Hong Kong Amendment and Good Clinical Practice Canadian Guidelines Written informed consent will be obtained from each participant The study results expected 18 months after commencement of recruitment will be disseminated at several levels including patients practitioners academicsresearchers and healthcare organizations
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None