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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Post Traumatic Stress Disorder
• Intervention / Treatment: Procedure: Repetitive Transcranial Magnetic Stimulation (rTMS); Procedure: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 102
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Florian FERRERI, MD, Ph; Phone Number: +33149282635; Email: florian.ferreri@aphp.fr

Study Locations

• France
  • Paris, France, 75012
    • Recruiting
    • Saint Antoine Hospital, Psychiatry department, Assistance Publique- Hôpitaux de Paris
    • Contact: Florian FERRERI, MD, PhD; Phone Number: +33149282635; Email: florian.ferreri@aphp.fr
    • Contact: Alexis BOURLA, MD; Phone Number: +33149282635; Email: alexis.bourla@aphp.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: rTMS with simultaneous reactivation of traumatic memory in resistant PTSD; rTMS with simultaneous reactivation of traumatic memory in resistant PTSD during 12 sessions (3 to 4 weeks)	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.
Placebo Comparator: sham rTMS and simultaneous reactivation of traumatic memory in resistant PTSD; sham rTMS and simultaneous reactivation of traumatic memory in resistant PTSD during 12 sessions (3 to 4 weeks)	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD severity score measured at M1 after 12 sessions of rTMS or sham rTMS and simultaneous reactivation of traumatic memory	CAPS-5 total severity score at M1 post treatment will be compared between groups (cerebral modulation by rTMS with simultaneous reactivation of traumatic memory VS sham rTMS with simultaneous reactivation of traumatic memory)	Month 1 after 12 sessions of rTMS

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PTSD severity scores at M3 and M6 measured with CAPS-5	The different dimensions of PTSD (assess by CAPS-5): Severity, repetition, avoidance, neurovegetative activation at M3 and M6 post treatment	At inclusion (v1), Month 3 and Month 6 post treatment
The severity of PTSD assessed by PCL-5 at each visit.	PTSD severity score measured with the PTSD Checklist (PCL-S self-questionnaire) at once a during TMS sessions, M1, M3 and M6 post treatment	at once a during TMS sessions, Month1, Month 3 and Month 6 post treatment.
Dissociative symptoms severity scores (1)	Dissociative symptoms severity score measured with the Clinician Administered Dissociative States Scale (CADSS)	at inclusion (V1), up to 4 weeks (V13) (end of treatment), Month 1, Month 3, Month 6 post treatment
Dissociative symptoms severity scores (2)	The Multidimensional Assessment of Interoceptive Awareness (MAIA)	at inclusion (V1), up to 4 weeks (V13) (end of treatment), Month 1, Month 3, Month 6 post treatment
Dissociative symptoms severity scores (3)	The Dissociative Experiences Scale (DES)	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.	The severity scores of the dimensions of anxiety measured with HAM-A at V13 (end of treatment), M1, M3 and M6.	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.	The severity scores of the dimensions of depression measured with HAM-D at V13 (end of treatment), M1, M3 and M6.	at V13 (end of treatment), Month 1, Month 3, Month 6 post treatment.
Evolution of social cognition at M3 post treatment.	Evolution of social cognition at M3 post treatment by a neuropsychologist	at Month 3 post treatment
Quality of life	Quality of life evolution post treatment and M6 assessed by WHOQOL EuroQol Health Measure	post treatment and Month 6
Quality of life	Quality of life evolution post treatment and M6 assessed by EQ-5D-5L	post treatment and Month 6
Proportion of adverse events during the active treatment phase and during the follow-up	Number and description of adverse events during the active treatment phase and during the follow-up	through study completion, up to 6 months

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Investigators: Principal Investigator: Florian FERRERI, MD, ph, Assistance Publique - Hôpitaux de Paris

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2024
• Primary Completion (Estimated): July 7, 2026
• Study Completion (Estimated): October 7, 2026

Study Registration Dates

• First Submitted: October 12, 2023
• First Submitted That Met QC Criteria: October 31, 2023
• First Posted (Actual): November 1, 2023

Study Record Updates

• Last Update Posted (Actual): May 8, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Mental Disorders; Stress Disorders; Traumatic Stress Disorders; Post-Traumatic Trauma and Stressor Related Disorders
• Additional Relevant MeSH Terms: Mental Disorders; Trauma and Stressor Related Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic
• Other Study ID Numbers: APHP200044; 2021-A02532-39-B (Other Identifier: IDRCB ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No