Transcranial Magnetic Stimulation for Psychological Distress in Patients With Advanced Illness
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18+
SponsorOttawa Hospital Research Institute
About this trial
Psychological and existential distress are a common cause of suffering among patients nearing the end of life, and a major reason for requesting medical aid in dying. Existing treatments for psychological and existential suffering have low efficacy and are challenging to use in a palliative context. There is a need to develop scalable, brief, and rapidly effective therapeutic approaches that can reduce psychological and existential distress in patients nearing the end of life.
Repetitive Transcranial Magnetic Stimulation is an effective treatment for refractory depression, and new protocols and increasing availability of rTMS may make this therapy feasible and acceptable for patients who suffer from psychological or existential distress near the end of life.
Among patients with advanced illness followed by a PC provider, the study objectives are to:
1. Identify the lowest and range of therapeutic rTMS dose to relieve psychological distress, including an analysis of clinical predictors of response. 2. Test the feasibility and preliminary efficacy of rTMS for the treatment of psychological distress including: 1) ease of recruitment; 2) completion of follow-up; 3) effect size and variance estimates of treatment for primary and secondary outcomes; and 4) patient satisfaction with treatment.
This study is a phase 2a dose-finding open-label clinical trial, followed by a phase 2b prospective, sham-control or sham-crossover study, depending on the therapeutic dose identified in phase 2a.
The investigators will enroll eligible patients from an inpatient palliative care unit and administer rTMS according to established best practice international guidelines. Two screening tests will be conducted (one completed by patient and another by the treating physician) to ensure the patient has no contraindications to rTMS. In the open-label dose-finding study, investigators will determine the appropriate dose of treatment that leads to positive patient outcomes, assess characteristics associated with positive and rapid response to rTMS, and examine if this treatment is feasible and acceptable to patients by measuring rates of enrollment and completion of the treatment sessions. Based on results from this first phase, a phase 2b feasibility and preliminary efficacy randomized clinical trial will be conducted to measure the effect of rTMS by comparing patient symptoms before and after the rTMS intervention.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
PC unit patients and PC patients in the community with advanced (terminal) illness
>1 month life expectancy
Experiencing psychological distress, as indicated by a score of 7 or greater on the Depression, Anxiety, or Well-being subscale of the Edmonton Symptom Assessment System (ESAS)
Ability to understand and communicate in English
Disqualifiers
Current or previously diagnosed seizure disorder or first-degree relative with current or previously diagnosed seizure disorder
Documented brain lesions
Inability to remain still while sitting up (45 degrees) for the duration of therapy
Known contraindications to rTMS, including: metallic skull plates, clips, or stimulators; pacemakers and other electronic implants; pregnancy; recurrent headaches with no known cause that do not respond to over-the-counter medications; current or previous skull fracture or traumatic brain injury; previous brain surgery; medications that lower seizure threshold
Trial design
Design model
Single group
Treatments tested in this trial
repetitive Transcranial Magnetic Stimulation (rTMS)
DeviceThe rTMS intervention will be performed in a dedicated rTMS patient room on the PC unit, where the patient can remain in their bed seated upwards at a 45 degree angle, or seated in a chair. The stimulation intensity for treatment will be determined by measuring the resting and active motor threshold (rMT and aMT) using single pulse TMS over the motor cortex using standard techniques as in previous trials. Investigators will use left-sided intermittent theta burst stimulation (iTBS). The trained team member will locate the left DLPFC using the BeamF3 technique. For the open-label dose-finding study, this region will be stimulated intermittently at 3 TMS pulses every 200 milliseconds for 2 seconds (i.e. 30 stimulations). This procedure is repeated every 10 seconds for a total duration of 3 minutes during which 600 total pulses are delivered. Participants will receive up to 8 3-minute sessions daily at 45 minute intervals for 5 days (consecutively or in a seven-day window if need be).
Treatment groups
15 Participants
are divided into 1 treatment groupGroup A: rTMS Intervention GroupExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Change in Psychological Distress, Depression
17-Item Hamilton Rating Scale for Depression (HRSD); scores 0-52; higher score is more severe depression
Time frame
Baseline (1 day prior to treatment start); after each day of rTMS treatment; 2 weeks, 4, and 8 weeks after intervention completion, if participant is alive2
Change in Psychological Distress, Depression and Anxiety
The Hospital Anxiety and Depression Scale (HADS); scores 0-21; higher score is more severe anxiety/depression
Time frame
Baseline (1 day prior to treatment start); after each day of rTMS treatment; 2 weeks, 4, and 8 weeks after intervention completion, if participant is alive3
Recruitment Rate
Total number of participants divided by the total number of eligible patients approached
Time frame
Measured upon study enrollment termination (estimated at 8 months for dose-finding study)4
Recruitment Rate
Total number of participants divided by the total number of eligible patients approached
Time frame
Measured upon study enrollment termination (estimated at 12 months for feasibility randomized clinical trial)Secondary outcomes
1
Anxiety
Hamilton Rating Scale for Anxiety; scores 0-30; higher score is more severe anxiety
Time frame
Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive2
Existential Distress
24-Item Demoralization (DEM) Scale; scores 0-96; higher score is more severe demoralization
Time frame
Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive3
Death Anxiety
Revised Death Anxiety Scale (RDAS) score; scores 15-75; higher score is more severe death anxiety
Time frame
Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is alive4
Participant Quality of Life: WHOQOL-Bref
World Health Organization Quality of Life Scale-brief version (WHOQOL-Bref); transformed scores range 4-20; higher score is higher quality of life
Time frame
Baseline (1 day prior to treatment start); end of last rTMS treatment day; 2 weeks, 4 weeks, 8 weeks, and 3 months after intervention completion, if participant is aliveSponsors and contacts
Click on the lead sponsor to view all of their trials.
Ottawa Hospital Research Institute
Lead sponsor
Lotte & John Hecht Memorial Foundation
Collaborator
Bruyère Health Research Institute.
Collaborator
Canadian Cancer Society (CCS)
Collaborator
Source ClinicalTrials.gov