Repetitive Transcranial Magnetic Stimulation Plus Reactivation Therapy Efficacy on PTSD Symptom Severity in Resistant PTSD

Official title

Repetitive Transcranial Magnetic Stimulation Plus Reactivation Therapy Efficacy on PTSD Symptom Severity in Resistant PTSD, a Randomized Double Blind Sham Controlled Trial (TraumaStim)

Overview

A French multicenter randomized and double blinded shamed controlled study recruiting patients who present resistant PTSD. The aim of this trial is to assess the efficacy of cerebral modulation by rTMS with simultaneous reactivation of traumatic memory on the PTSD symptoms at M1.

Detailed description

Detailed Description : PTSD is considered as one of the top 10 public health concerns. Most patients with PTSD receive pharmacologic treatment and traumatic reactivation therapy. However, to date, the optimal treatment alternatives for non-responders PTSD patients are unknown.

Functionally, the metabolic activity of the prefrontal-amygdala cortex circuit in PTSD is significantly altered. Repetitive Transcranial Magnetic Stimulation (rTMS) provides focused, non-invasive stimulation of cortical areas of the central nervous system and could correct cortical defective activation of the prefrontal cortex seen in PTSD Patient (FDA has already approved rTMS for depression and acoustic-verbal hallucinations treatment).

Pairing rTMS with cues relevant to the trauma may be a novel approach to treat PTSD patient.

The study will enroll 102 subjects with resistant PTSD. After screening and inclusion phase, the treatment phase with 12 sessions of rTMS and simultaneous reactivation of traumatic memory or sham rTMS and simultaneous reactivation of traumatic memory will be performed (3 to 4 weeks). Antidepressant treatment will be maintained. The follow up phase consist of 3 visits at M1, M3 and M6 to follow the evolution of the PTSD symptoms.

Interventions

• Procedure Repetitive Transcranial Magnetic Stimulation (rTMS)
  rTMS with simultaneous reactivation of traumatic memory will be performed 3 to 4 times a week for 3 to 4 weeks through 12 sessions. A traumatic script will be prepared by the patient at the inclusion visit, which will be used to reactivate the traumatic memory after every rTMS or sham rTMS sessions.
• Procedure Placebo
  sham rTMS with simultaneous reactivation of traumatic memory will be performed 3 to 4 times a week for 3 to 4 weeks through 12 sessions. A traumatic script will be prepared by the patient at the inclusion visit, which will be used to reactivate the traumatic memory after every rTMS or sham rTMS sessions.

Primary outcome measures

• PTSD severity score measured at M1 after 12 sessions of rTMS or sham rTMS and simultaneous reactivation of traumatic memory [Time frame: Month 1 after 12 sessions of rTMS]

Secondary outcome measures (11)

• PTSD severity scores at M3 and M6 measured with CAPS-5 [Time frame: At inclusion (v1), Month 3 and Month 6 post treatment]
• The severity of PTSD assessed by PCL-5 at each visit. [Time frame: at once a during TMS sessions, Month1, Month 3 and Month 6 post treatment.]
• Dissociative symptoms severity scores (1) [Time frame: at inclusion (V1), up to 4 weeks (V13) (end of treatment), Month 1, Month 3, Month 6 post treatment]
• Dissociative symptoms severity scores (2) [Time frame: at inclusion (V1), up to 4 weeks (V13) (end of treatment), Month 1, Month 3, Month 6 post treatment]
• Dissociative symptoms severity scores (3) [Time frame: at inclusion (V1), up to 4 weeks (V13) (end of treatment), Month 1, Month 3, Month 6 post treatment]
• The severity scores of the dimensions of anxiety at V13 (end of treatment), M1, M3, M6 post treatment. [Time frame: Up to 4 weeks (V13) (end of treatment), Month 1, Month 3, Month 6 post treatment.]
• Symptoms of depression at V13 (end of treatment), M1, M3, M6 post treatment. [Time frame: at V13 (end of treatment), Month 1, Month 3, Month 6 post treatment.]
• Evolution of social cognition at M3 post treatment. [Time frame: at Month 3 post treatment]
• Quality of life [Time frame: post treatment and Month 6]
• Quality of life [Time frame: post treatment and Month 6]
• Proportion of adverse events during the active treatment phase and during the follow-up [Time frame: through study completion, up to 6 months]

Eligibility criteria

Inclusion criteria

• Patients aged between 18 and 65 years.
• Presenting a PTSD according to DSM-5 criteria
• Patient with persistent symptoms (PCL-5>40) after a 6 weeks treatment with labelled antidepressant for PTSD (paroxetine or sertraline)
• Patient with health insurance (AME excepted)
• Signed written inform consent

Exclusion criteria

• Contraindication for rTMS:

• History of epilepsy or seizure
• Cochlear implants
• Cardiac pacemaker or intracardiac lines, or metal in the body
• Patient has already had a rTMS session and/or Electroconvulsive therapy (ECT) and/or Transcranial direct current stimulation (tDCS)
• Ongoing PTSD-oriented cognitive-behavioral therapy
• Lifetime psychotic or bipolar disorder or antisocial personality or borderline personality
• Brain injury defined by medical report (including cortical and subcortical atrophy, dementia, stroke, transient ischemic attack and head trauma)
• Current substance dependence (including alcohol, excluding tobacco);
• Acute suicidal ideation
• No adequate mastering of the French language or no ability to consent
• Pregnancy (confirmed by a urine test beta-HCG) or breast feeding or absence of birth control
• Patient under legal protection measure and or deprived of freedom
• Participation in any other interventional study or in the exclusion period any other interventional study

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

France · 1 center

• Saint Antoine Hospital, Psychiatry department, Assistance Publique- Hôpitaux de Paris — Paris

Identifiers

NCT: NCT06111976 · APHP200044 · 2021-A02532-39-B

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗