Neurostimulation for treating severe PTSD

Responsive Neurostimulation for Post-Traumatic Stress Disorder

This study is testing whether a new brain stimulation device can help people with severe PTSD who haven't found relief from other treatments.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 6 (estimated)
• Ages: 25 Years to 60 Years
• Sex: Male
• Sponsor: VA Greater Los Angeles Healthcare System (Federal)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Los Angeles, California)
• Trial ID: NCT04152993 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of the NeuroPace® RNS® System to provide responsive neurostimulation for patients suffering from treatment-refractory post-traumatic stress disorder (PTSD). The study focuses on the biological mechanisms of fear extinction and aims to modulate activity in the basolateral amygdala, a key area involved in emotional processing. Participants will undergo a 4-year follow-up period, during which their responses to the neurostimulation will be assessed. The trial seeks to provide insights into the effectiveness of this neuromodulation approach in alleviating PTSD symptoms.

Who should consider this trial

Good fit: Ideal candidates are males aged 25-60 with chronic, treatment-refractory PTSD who have not responded to standard therapies.

Not a fit: Patients with PTSD who have not reached a stage of treatment resistance or those who do not meet the age and gender criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life for patients with severe, treatment-resistant PTSD.

How similar studies have performed: Previous studies have shown promise in using neuromodulation techniques for PTSD, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

1. Male aged 25-60 years.
2. Able to give informed consent in accordance with institutional policies and participate in the 4-year follow-up, involving assessments and stimulator adjustments.
3. Patients must be stable on their current psychotropic medication for a period of 2 months before implantation and agree to not increase dosages or add any new medications for the first 6 months of the study, unless medically necessary.
4. Chart diagnosis of chronic and treatment-refractory PTSD as the principal psychiatric diagnosis and cause of distress and social/occupational impairment.
5. Confirmation of PTSD as the primary psychiatric diagnosis by the study psychiatrist via clinical interview and CAPS.
6. Minimum 5-year total illness duration, with no 6-month period of clinical remission during the 2 years prior to entry in the study.
7. Stage 2 level of treatment resistance as per Sippel et al.136: Clinical record documented failure to respond to adequate (minimum 3 month, with adherence) trials of at least 3 of the following evidence-based treatments including at least one pharmacologic agent below, and at least one trauma-focused individual cognitive-behavior psychotherapy among the following: Pharmacologic: sertraline, paroxetine, fluoxetine or venlafaxine, at maximally tolerated FDA recommended doses. Psychotherapy: Prolonged Exposure Therapy (PE); Cognitive Processing Therapy (CPT); Eye movement Desensitization and Reprocessing (EMDR); or other form of evidence-based cognitive behavior therapy for PTSD
8. Patients who are unable to complete trauma-focused psychotherapy may be included if they began treatment, and the cause of treatment cessation was that the risks of further treatment, including intense psychological suffering, outweighed the potential benefits of continuing the treatment.
9. All evidence-based psychotherapy for PTSD has been completed a minimum of 3 months prior to enrolment.
10. Minimum baseline past month CAPS-5 Score of 47, with full PTSD diagnostic criteria met, and scores of ≥ 3 on at least one item from the intrusive (CAPS-5 items 1-5) and hyperarousal (CAPS-5 Items 15-20) clusters; and this severity maintained for at least one month during the baseline period based on two separate measures.
11. Clinically significant impairment in occupational functioning due to PTSD, manifested by one or more of the following: a) Total federal (service connected ≥ 70%), or State (SSI) disability compensation for at least the past 2 years for PTSD; b) global assessment of functioning score ≤ 45; c) no period of full time gainful employment ≥ 3 months in the past 5 years. Or clinically significant impairment in social functioning due to PTSD, manifested by one or more of the following: (i) little or no social activity outside the household other than as necessary for medical appointments, practical matters such as grocery shopping, or to interact with other veterans; (ii) reliable description by a spouse or significant other, living with the patient, of repeated avoidance/refusal to participate in customary social engagements with friends, family or for recreational activities due to PTSD; (iii) two or more verbal or physical interpersonal altercations within the past year requiring another person's intervention to prevent further escalation, or involving law enforcement.
12. Presence in the veteran's life of a spouse, family member or friend who can confirm the symptoms and impairment from PTSD and lack of symptomatic remission in the past 2 years; participate with the study psychiatrist in answering questions about symptoms and functioning at scheduled follow-up visits; and report unexpected adverse neurological or psychiatric events to study investigators and, if advised by study investigators, assist the patient in accessing necessary services to address obtain care.
13. Willingness to have unexpected neurological or psychiatric symptom shared with the study psychiatrists and other study clinicians.
14. Other medical conditions must be stable for at least 1 year, (conditions that require intermittent use of steroids or chemotherapy are excluded).

Exclusion Criteria:

1. Suicide attempt in the last 2 years and/or presence of a suicide plan (an answer of "Yes" to Question C4 in Section C-Suicidality of MINI International Neuropsychiatric Interview);
2. Unstable psychosis or bipolar disorder; significant acute or ongoing risk for violence;
3. Patients primarily diagnosed with DSM-IV-TR Axis I disorder other than PTSD as determined by the MINI;
4. Within the 3 months prior to enrolment, subject has started a new psychotherapy program;
5. Alcohol or illicit substance use disorder within the last 6 months, unstable remission of substance abuse, or chart evidence that co-morbid substance use disorder could account for lack of treatment response;
6. Current significant neurological conditions, including epilepsy, stroke, movement disorder; history of serious head injury with loss of consciousness if associated with neurological or neuropsychological deficit that could interfere with study participation or outcome assessment; or if associated with structural MRI abnormality.
7. Uncontrolled medical condition including cardiovascular problems and diabetes;
8. Uncontrolled chronic pain;
9. Baseline Montgomery Asberg Depression Rating Scale (MADRS) of ≥ 28;
10. Use of warfarin;
11. Significant abnormality on preoperative structural brain MRI;
12. ECT in the past 6 months;
13. Contraindications to MRIs or the need for recurrent body MRIs;
14. Immunosuppression;
15. High risk for surgery;
16. Current pursuit of new or increased disability compensation for PTSD;
17. Intracranial implants (aneurysm clip, shunt, cochlear implant, electrodes);
18. Patient has had past cranial neurosurgery;
19. Use of other investigational drugs within 30 days of baseline.
20. Patients suffering from a neurovascular condition or other intracranial process.
21. Patients suffering from a condition associated with a significant cognitive impairment.

Where this trial is running

Los Angeles, California

• VA Greater Los Angeles — Los Angeles, California, United States (Recruiting)

Study contacts

• Study coordinator: Sonja Hiller

Conditions Post-Traumatic Stress Disorder