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

Not Applicable

Recruiting

• Conditions: Post Traumatic Stress Disorder
• Interventions: Procedure: Repetitive Transcranial Magnetic Stimulation (rTMS); Procedure: Placebo

• Registration Number: NCT06111976
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

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.

Study Timeline

• Study First Submitted: 2023-10-12
• Study First Submitted QC: 2023-10-31
• Study First Posted: 2023-11-01
• Study Start: 2024-03-07
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-08
• Primary Completion: 2026-07-07
• Study Completion: 2026-10-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 102

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
rTMS with simultaneous reactivation of traumatic memory in resistant PTSD	Repetitive Transcranial Magnetic Stimulation (rTMS)	rTMS with simultaneous reactivation of traumatic memory in resistant PTSD during 12 sessions (3 to 4 weeks)
sham rTMS and simultaneous reactivation of traumatic memory in resistant PTSD	Placebo	sham rTMS and simultaneous reactivation of traumatic memory in resistant PTSD during 12 sessions (3 to 4 weeks)

Primary Outcome Measures

Name	Time	Method
PTSD severity score measured at M1 after 12 sessions of rTMS or sham rTMS and simultaneous reactivation of traumatic memory	Month 1 after 12 sessions of rTMS	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)

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Saint Antoine Hospital, Psychiatry department, Assistance Publique- Hôpitaux de Paris; 🇫🇷 Paris, France