PTSD - Post Traumatic Stress DisorderPhase 2NCT06639061
Neuromodulation of the Hippocampus to Reduce Intrusive Re-Experiencing in PTSD: A Randomized Controlled Trial
A Phase 2 study testing Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS) in people with PTSD - Post Traumatic Stress Disorder and Intrusive Memories of Traumatic Event(s), run by Tel Aviv University at 1 site in Israel.
Trial 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). Read more about this study
- Who is it for?
- Ages 20 to 65 years
- Conditions the study is for
- PTSD - Post Traumatic Stress Disorder, Intrusive Memories of Traumatic Event(s)
- What is being tested?
- Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS)
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Nov 2024to Nov 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- Meeting the accepted criteria for inclusion in an MRI examination.
Who cannot join
- 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.
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- 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.
- The accepted exclusion criteria for an MRI examination
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Tel Aviv University
Tel Aviv
Yair Bar-Haim, PhD, 972-3-6405465, yair1@tauex.tau.ac.il
Nitzan Censor, PhD, 972-3-6406105, censornitzan@tauex.tau.ac.il
About this study
Official title: Characterization and Modulation of Traumatic Memories in PTSD Patients Using Transcranial Magnetic Stimulation (TMS)
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.
Read more
Participants will:
- 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.
- Receive hippocampus neuromodulation or a control neuromodulation once a week for 5 weeks.
Keep a daily diary of their symptoms and the number of times they experience intrusive trauma memories.
Read the detailed description
Intrusive trauma memories are a hallmark of posttraumatic stress disorder (PTSD), and the least treatment responsive. Thus, revealing neurocognitive mechanisms associated with intrusive trauma memories has been indexed a priority. Prior work shows that targeting hippocampal circuitry modulates functional connectivity among distributed cortical-hippocampal network regions and alters memory performance in healthy participants. In the current clinical trial we test hypotheses on the clinical effects of such stimulation in a two-arms randomized controlled trial: Trauma memory reactivation + targeted hippocampal transcranial magnetic stimulation TMS (R-H-TMS) and Trauma memory reactivation + Control TMS (over the SMA; R-C-TMS). We will test a) Hippocampus seed-based connectivity patterns - revealing the impact of the targeted stimulation on extended memory brain networks; and b) frequency and severity of intrusive memory symptoms. The R-H-TMS vs. R-C-TMS contrast will speak to specificity of the noted effects to hippocampal stimulation.
- Being tested
- Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS), Sham stimulation using repetitive transcranial magnetic stimulation (rTMS)
- Keywords
- PTSD, TMS, MRI
- Medical subject headings
- Combat Disorders, Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS)Device
Also called TMS, MRI
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.
Sham stimulation using repetitive transcranial magnetic stimulation (rTMS)Device
Also called TMS, MRI
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Sham stimulation using repetitive transcranial magnetic stimulation (rTMS) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 6 weeks, 3-months
Secondary outcomes (3)
PTSD Checklist for DSM-5 (PCL-5)
The PCL-5 is a 20-item self-reported measured based on the DSM-5 PTSD symptoms and assessing PTSD symptoms endorsement and severity.
Measured: Baseline, 6 weeks, 3-months
Intrusive trauma memories diary
The amount, frequency and emotional effect of intrusive traumatic memories, measured by a daily self-report digital diary.
Measured: Through study completion, an average of 8 weeks
Patient Health Questionnaire - 9 (PHQ-9)
Measures severity of depression symptoms as listed in the DSM-5
Measured: Baseline, 6 weeks, 3-months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start1 Nov 2024
- Primary completionOct 2027 (estimated)
- Study completionNov 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PTSD - Post Traumatic Stress DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tel Aviv University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yair Bar-Haim, Tel Aviv University
- Investigators
- Yair Bar-Haim, PhD, Principal investigator, Tel Aviv University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06639061
- Sponsor's protocol ID
- 0004373-5
- Other IDs
- 101141436 - TraumaNeuroInsight
- Status last verified
- Oct 2024
- First submitted
- 9 Oct 2024
- Last updated
- 1 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data from the study will be shared in accordance with local laws related to patient data sharing.
Study at a glance
From the registry record, last updated by the sponsor on 1 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization and Modulation of Traumatic Memories in PTSD Patients Using Transcranial Magnetic Stimulation (TMS)
- ClinicalTrials.gov ID
- NCT06639061
- Acronym / sponsor ID
- 0004373-5
- Keywords
- PTSD, TMS, MRI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Tel Aviv UniversityUniversity, hospital or other
- Study start
- 1 Nov 2024 (actual)
- Primary completion
- Oct 2027 (estimated)
- Study completion
- Nov 2028 (estimated)
- First posted
- 15 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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.
- Receive hippocampus neuromodulation or a control neuromodulation once a week for 5 weeks.
Keep a daily diary of their symptoms and the number of times they experience intrusive trauma memories.
Detailed description
Intrusive trauma memories are a hallmark of posttraumatic stress disorder (PTSD), and the least treatment responsive. Thus, revealing neurocognitive mechanisms associated with intrusive trauma memories has been indexed a priority. Prior work shows that targeting hippocampal circuitry modulates functional connectivity among distributed cortical-hippocampal network regions and alters memory performance in healthy participants. In the current clinical trial we test hypotheses on the clinical effects of such stimulation in a two-arms randomized controlled trial: Trauma memory reactivation + targeted hippocampal transcranial magnetic stimulation TMS (R-H-TMS) and Trauma memory reactivation + Control TMS (over the SMA; R-C-TMS). We will test a) Hippocampus seed-based connectivity patterns - revealing the impact of the targeted stimulation on extended memory brain networks; and b) frequency and severity of intrusive memory symptoms. The R-H-TMS vs. R-C-TMS contrast will speak to specificity of the noted effects to hippocampal stimulation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Trauma memory reactivation + targeted hippocampal TMS | Active comparator | Device: Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS)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. |
| Trauma memory reactivation + targeted sham TMS | Sham comparator | Device: Sham stimulation using repetitive transcranial magnetic stimulation (rTMS)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. |
Who may qualify
- Ages
- 20 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
- Meeting the accepted criteria for inclusion in an MRI examination.
Key exclusion criteria (13 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS)Also: TMS, MRIWe 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. | Device | Trauma memory reactivation + targeted hippocampal TMS |
| Sham stimulation using repetitive transcranial magnetic stimulation (rTMS)Also: TMS, MRIWe 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. | Device | Trauma memory reactivation + targeted sham TMS |
Primary outcome
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total score
Time frame: Baseline, 6 weeks, 3-months
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.
3 secondary outcomes
PTSD Checklist for DSM-5 (PCL-5)
Time frame: Baseline, 6 weeks, 3-months
Intrusive trauma memories diary
Time frame: Through study completion, an average of 8 weeks
Patient Health Questionnaire - 9 (PHQ-9)
Time frame: Baseline, 6 weeks, 3-months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Nov 2024.
- Individual participant dataSharing planned: Yes. De-identified data from the study will be shared in accordance with local laws related to patient data sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yair Bar-Haim, PhD principal investigator
Tel Aviv University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hippocampal stimulation using repetitive transcranial magnetic stimulation (rTMS) in people with PTSD - Post Traumatic Stress Disorder and Intrusive Memories of Traumatic Event(s), run by Tel Aviv University at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yair Bar-Haim, PhD (972-3-6405465, yair1@tauex.tau.ac.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) Total score (time frame: Baseline, 6 weeks, 3-months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Nov 2024.