Pathophysiological Understanding and Treatment of PTSD: an rTMS Approach

U

University of Calgary

Status

Completed

Conditions

Brain Injuries
Biomarkers
Depression, Anxiety
Stress Disorders, Post-Traumatic
Transcranial Magnetic Stimulation
Magnetic Resonance Spectroscopy

Treatments

Device: Sham Repetitive Transcranial Magnetic Stimulation
Device: Repetitive Transcranial Magnetic Stimulation to Right Dorsomedial Prefrontal Cortex
Device: Repetitive Transcranial Magnetic Stimulation to Right Dorsolateral Prefrontal Cortex

Study type

Interventional

Funder types

Other
Industry

Identifiers

NCT03840369
REB18-1976

Details and patient eligibility

About

In Canada, the prevalence of PTSD is approximately 12%, similar to Canadian military personnel. Current treatments for PTSD are limited in efficacy and durability - indicating a dire need for novel interventions in this population. Transcranial magnetic stimulation (TMS) has a high degree of safety and has been studied as an intervention for many mental health and neurological conditions; even showing initial promise for PTSD. We propose to study this further in a randomized sham controlled trial of TMS for PTSD.

Full description

In Canada, the prevalence of PTSD is approximately 12%, similar to Canadian military personnel. However, a 2002 study of members of Canadian Armed Forces found there was a striking positive correlation between the number of missions taken by the regular/reserve force and increase risk of developing PTSD, suggesting a dire need for further treatment options. Transcranial magnetic stimulation (TMS), a neuromodulation technique applied to the brain, has been studied as a treatment that has the potential to improve symptoms in a variety of neurological/mental health conditions. TMS is a safe and non-invasive technique that applies an electrical current to the brain to induce neuronal depolarization, changing regional brain function with the goal of improving neurological/psychiatric symptoms. Although multiple studies using TMS have suggested it as an efficacious treatment option for PTSD, clear knowledge gaps exist that prevent it from becoming evidence-based clinical care. A recent meta-analysis on TMS and PTSD found that no study has examined the difference between genders, and recommended that further studies with larger sample sizes, equal male and female participants, and more stringent study designs were required. Our study is novel and seeks to bridge the gap from research to clinical care by completing a study investigating repetitive TMS (rTMS) treatment for PTSD that recruits a large sample size, uses a randomized controlled clinical trial with a sham lead-in, and follows a stringent TMS protocol with equal sex participants. Not all individuals with PTSD respond to TMS treatment, and no study to date has explored what biomarkers may predict TMS responders in the PTSD population. Previous studies propose glutamate, BDNF and glutamatergic changes on MR spectroscopy may be altered in other mental health illnesses, which suggests they may be useful biomarkers of TMS response in PTSD. Therefore, this study will be the first of its kind to develop predictive biomarkers of response by sampling serum BDNF, glutamate, and glutamatergic changes in MR spectroscopy pre- and post rTMS treatment, in patients with PTSD that respond to TMS compared to those that do not. Recent studies have shown single-pulse TMS is beneficial for some individuals with chronic PTSD, and emerging evidence suggests there are specific phenotypes within PTSD that may require different TMS protocols. A recent study by Etkin et al. explored whether there were multiple phenotypes within chronic PTSD that would explain treatment responses. They found individuals with PTSD that scored significantly lower on verbal memory tasks (LVMS) (list repetition) had significantly impaired functional connectivity in the brain's ventral attention network (VAN) compared to patients with PTSD that had normal scores (NVMS). This suggests there may be a subgroup of patients with PTSD that would respond better to TMS in the right dorsal medial prefrontal cortex (DMPFC) (corresponding to the VAN) than to the right dorsal lateral prefrontal cortex (DLPFC).

Enrollment

25 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Adult participants represent a typically developing nervous system as a more reliable target for this stage of research.
  • The presence of a PTSD diagnosis made by a physician will ensure participants are experiencing significant symptomatology and may benefit from treatment.
  • The cutoff score on the PCL-5 will ensure that participants are experiencing similar levels of symptoms to each other.
  • Need to have tried at least two types of treatment in the past

Exclusion criteria

  • Significant past medical history including seizures, stroke, severe traumatic brain injury, or central nervous system cancers may interfere with our evaluation of treatment outcome and will be criteria for exclusion.
  • Metal in head/neck/eye is a contraindication to safety in the MRI scanner and TMS protocol.
  • Women who are pregnant will not be included in the study due to potential risk of seizure during TMS. To determine if a patient is pregnant we will ask when their last menstrual cycle occurred. If there is a possibility of pregnancy, we will ask the participant to follow-up with their family doctor to confirm. We will then ask the participant to provide a written note from their treating practitioner stating they are not pregnant.
  • Active suicidality
  • Wellbutrin or benzodiazepine intake of more than 200mg/day, or more than 15 mg of Zopiclone per day as these medications lower seizure threshold
  • Trauma experienced less than a year ago and/or trauma experienced only as a child
  • Drug and/or alcohol abuse within the last 3 months (diagnosed by Canadian guidelines)
  • Diagnosed schizophrenia, untreated bipolar disorder, or psychosis

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

25 participants in 2 patient groups

rTMS to the Right Dorsolateral Prefrontal Cortex
Experimental group
Description:
Patients will engage in a one-week placebo control lead-in (5 treatments) and then a four-week treatment protocol (20 treatments) to the right Dorsolateral Prefrontal Cortex (DLPFC). The right DLPFC will be located with MR brain scans and the BrainSight TMS neuronavigation software. The intensity of the rTMS will be 100-120% of resting motor threshold amplitude, 1500 pulses applied consistently with a frequency of 1 Hz.
Treatment:
Device: Repetitive Transcranial Magnetic Stimulation to Right Dorsolateral Prefrontal Cortex
Device: Sham Repetitive Transcranial Magnetic Stimulation
rTMS to the Right Dorsomedial Prefrontal Cortex
Experimental group
Description:
Patients will engage in a one-week placebo control lead-in (5 treatments) and then a four-week treatment protocol (20 treatments) to the right Dorsomedial Prefrontal Cortex (DMPFC). The right DMPFC will be located with MR brain scans and the BrainSight TMS neuronavigation software. The intensity of the rTMS will be 100-120% of resting motor threshold amplitude, 1500 pulses applied consistently with a frequency of 1 Hz.
Treatment:
Device: Repetitive Transcranial Magnetic Stimulation to Right Dorsomedial Prefrontal Cortex
Device: Sham Repetitive Transcranial Magnetic Stimulation

Trial contacts and locations

1

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems