Neuromodulation of the Hippocampus to Reduce Intrusive Re-Experiencing in PTSD: A Randomized Controlled Trial

NCT06639061 | Recruiting Phase 2

• 2 other identifiers: 0004373-5101141436 - TraumaNeuroInsight
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if non-invasive neurostimulation of memory-related brain areas works to treat intrusive memory symptoms in adults patients with posttraumatic stress disorder (PTSD). It will also learn about the effect of this neuromodulation procedure on reorganization of memory-related brain networks. The main questions it aims to answer are: Does neuromodulation lower the number of times and the emotional severity participants intrusive memories? Does neuromodulation reduces the overall severity of PTSD? Researchers will compare neuromodulation targeting the hippocampus (a memory-related brain structure) to a control stimulation in an area not related to memory processes to see if hippocampus neuromodulation works to treat intrusive trauma memories and PTSD. Participants will:

1. 1.Undergo magnetic resonance imaging (MRI) scans before and after neuromodulation to: a) determine a personalized neuromodulation target; and b) to measure changes in brain function from before to after treatment.
2. 2.Receive hippocampus neuromodulation or a control neuromodulation once a week for 5 weeks.

Conditions

PTSD - Post Traumatic Stress Disorder; Intrusive Memories of Traumatic Event(s)

Keywords

PTSD; TMS; MRI

Outcome Measures

Primary Outcomes (1)

• Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total score

  The CAPS-5 is a 30-item structured interview that can be used to make current (past month or week) diagnosis of PTSD \& make lifetime diagnosis of PTSD.

  Baseline, 6 weeks, 3-months

Secondary Outcomes (3)

• PTSD Checklist for DSM-5 (PCL-5)

  Baseline, 6 weeks, 3-months

• Intrusive trauma memories diary

  Through study completion, an average of 8 weeks

• Patient Health Questionnaire - 9 (PHQ-9)

  Baseline, 6 weeks, 3-months

Other Outcomes (2)

• credibility/expectancy questionnaire (CEQ)

  Baseline

• fMRI Neuroimaging

  Baseline, 6 weeks

Study Arms (2)

Trauma memory reactivation + targeted hippocampal TMS

ACTIVE COMPARATOR

Brain stimulation using repetitive transcranial magnetic stimulation (rTMS) will be given after a deliberate memory re-activation, using repetitive pulses at 1Hz frequency for 15 minutes, once a week over 5 weeks. The scalp stimulation area will be determined based on a resting state fMRI scan identifying a cortical area that is most strongly functionally connected to the left hippocampal target of each patient.

Device: Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS)

Trauma memory reactivation + targeted sham TMS

SHAM COMPARATOR

Brain stimulation using repetitive transcranial magnetic stimulation (rTMS) will be given after a deliberate memory re-activation, using repetitive pulses at 1Hz frequency for 15 minutes, once a week over 5 weeks. The scalp stimulation area will be determined based on a resting state fMRI scan identifying a cortical area that has near zero functional connectivity with the left hippocampal target of each patient.

Device: Sham stimulation using repetitive transcranial magnetic stimulation (rTMS)

Interventions

Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS) DEVICE

We will use fMRI resting state data to personalize a TMS inhibitory stimulation to a cortical location that is the most strongly connected to a deeper left hippocampal target. 5 once a week sessions of rTMS will be delivered at 1-Hz stimulation frequency for 15 minutes following trauma memory reactivation.

Also known as: TMS, MRI

Trauma memory reactivation + targeted hippocampal TMS

Sham stimulation using repetitive transcranial magnetic stimulation (rTMS) DEVICE

We will use fMRI resting state data to personalize a TMS sham stimulation to a cortical location with near zero connectivity to a deeper left hippocampal target. 5 once a week sessions of rTMS will be delivered at 1-Hz stimulation frequency for 15 minutes following trauma memory reactivation.

Also known as: TMS, MRI

Trauma memory reactivation + targeted sham TMS

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged of 20-65 years.
• Meet a diagnosis of PTSD according to DSM-5 as tested by a structured clinical interview (Clinician-Administered PTSD Scale for DSM-5 - CAPS-5).
• CAPS-5 total score greater or equal to 33.
• Endorsement of intrusive symptoms (flashbacks, nightmares, or intrusive memories) with a frequency of at least 3 times a week.

You may not qualify if:

• Meeting a diagnosis of Complex PTSD or personality disorder.
• Psychotic disorder, bipolar disorder, or a developmental neuropsychological disorder (autism, mental retardation).
• Use of psychiatric medications (except for the medications listed in section 4.a of the study protocol if the medication dosage is stable in the last three months and does not change during the study.
• Use of the following drugs: imipramine, amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine, foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, (MDMA, ecstasy), phencyclidine (PCP, angel's dust), ketamine, gamma- hydroxybutyrate (GHB), alcohol, theophylline
• Epilepsy or use of anti-epileptic drugs.
• Traumatic head injuries or head surgery.
• Implanted metallic body (except fillings/amalgam bites/orthodontic fixations approved for MRI), electrodes or a pacemaker.
• Migraines
• Pregnant women
• Hearing problems
• Drinking alcohol 24 hours before the TMS session
• Repeated episodes of fainting with loss of consciousness and/or an event of fainting with loss of consciousness in the past year.

Sponsors & Collaborators

• Tel Aviv University: lead

Study Sites (1)

Tel Aviv University

Tel Aviv, Israel

RECRUITING

MeSH Terms

Conditions

Combat Disorders; Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Study Officials

• Yair Bar-Haim, PhD

  Tel Aviv University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yair Bar-Haim, PhD

CONTACT

972-3-6405465; yair1@tauex.tau.ac.il

Nitzan Censor, PhD

CONTACT

972-3-6406105; censornitzan@tauex.tau.ac.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: October 9, 2024
• First Posted: October 15, 2024
• Study Start: November 1, 2024
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): November 1, 2028
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Uploaded by October 2026 (before data analyses starts), will stay on.
• Access Criteria: Deidentified clinical outcome data will be deposited in an open access repository in compliance with local patient information sharing laws. Reference to the repository will be embedded in the published report for unrestricted access. De-identified MRI data matrices will be shared upon request and in compliance with local patient information sharing laws.

Locations

IL (1)