Transcranial Magnetic Stimulation for Psychological Distress in Patients With Advanced Illness

Summary

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.

Conditions

• Depressive Symptoms
• Depression, Anxiety
• Psychological Distress
• Terminal Illness

Interventions

DEVICE

repetitive Transcranial Magnetic Stimulation (rTMS)

The 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).

Sponsors & Collaborators

• Lotte & John Hecht Memorial Foundation

  collaborator OTHER

• Bruyère Health Research Institute.

  collaborator OTHER

• Canadian Cancer Society (CCS)

  collaborator OTHER

• Ottawa Hospital Research Institute

  lead OTHER

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2020-11-02

Primary Completion

2025-01-20

Completion

2025-01-20

Countries

• Canada

Study Locations