Deep Brain Stimulation of the Amygdala for Combat Post-Traumatic Stress Disorder

NCT02091843 | Unknown DMC

• 1 other identifier: PCC121657
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

Posttraumatic stress disorder (PTSD) affects approximately 30 % of American veterans returning from Iraq and Afghanistan. Although the current therapy is effective, a percentage of patients will fail to improve and will develop chronic treatment-resistant PTSD. Patients suffering from PTSD experience intense suffering, lack of productivity and a higher risk of suicide. Unfortunately, combat PTSD has a tendency to be resistant to current treatments. The central goal of this project is to develop a new therapeutic strategy involving the placement of intracranial electrodes to treat the symptoms of PTSD. The project is based on recent evidence showing abnormal activity in a specific brain region of PTSD patients, thought to be responsible for the core symptoms of PTSD.

Conditions

Posttraumatic Stress Disorder

Outcome Measures

Primary Outcomes (1)

• Frequency and Severity of all adverse events

  1 year

Secondary Outcomes (1)

• Clinician-Administered PTSD Scale

  1 year

Study Arms (2)

DBS of the Amygdala-30 days

EXPERIMENTAL

Deep brain stimulation of the amygdala BLn starting at 30 days post-operatively.

Procedure: DBS of the Basolateral Nucleus of the Amygdala; Device: Medtronic Activa PC DBS of the Basolateral Nucleus of the Amygdala

DBS of the Amygdala-90 days

EXPERIMENTAL

Deep brain stimulation of the amygdala BLn starting at 90 days post-operatively.

Procedure: DBS of the Basolateral Nucleus of the Amygdala; Device: Medtronic Activa PC DBS of the Basolateral Nucleus of the Amygdala

Interventions

DBS of the Basolateral Nucleus of the Amygdala PROCEDURE

DBS of the Amygdala-30 days; DBS of the Amygdala-90 days

Medtronic Activa PC DBS of the Basolateral Nucleus of the Amygdala DEVICE

DBS of the Amygdala-30 days; DBS of the Amygdala-90 days

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male aged 25-70 years.
• Able to give informed consent in accordance with institutional policies and participate in the 2-year follow-up, involving assessments and stimulator adjustments.
• 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.
• Chart diagnosis of chronic and treatment-refractory PTSD as the principal psychiatric diagnosis and cause of distress and social/occupational impairment.
• Confirmation of PTSD as the primary psychiatric diagnosis by the study psychiatrist via clinical interview and CAPS.
• Confirmation of combat trauma exposure via military record review and a Combat Exposure Scale score \> 9.
• Minimum 5 year total illness duration, with no 6 month period of clinical remission during the 5 years prior to entry in the study.
• Clinical record documentation of non-response to at least 2 of the following antidepressants, alone or in combination, at maximally tolerated FDA recommended doses for ≥ 6 months: sertraline, paroxetine, fluoxetine, citalopram, escitalopram, amitriptyline, imipramine, nortriptyline, desipramine, clomipramine, phenelzine, tranylcypromine, venlafaxine, mirtazapine. Antidepressant trials must include at least one SSRI and one SNRI or TCA at maximally tolerated FDA recommended doses for a minimum of 3 months.
• A minimum 3 month trial of prazosin at 10 mg per day or, if less, maximally tolerated FDA recommended doses, unless considered contraindicated based on co-morbid medical conditions or concomitant medications.
• Trial of at least 3 months of one of the following: lithium, divalproex sodium, carbamazepine, lamotrigine, olanzapine, risperidone, bupropion either alone or in conjunction with one or more of the agents in #8 and # 9 above.
• All evidence based psychotherapy for PTSD (cognitive behavioural, cognitive processing, prolonged exposure, eye movement desensitization) has been completed a minimum of 3 months prior to enrolment.
• Minimum baseline CAPS17 of 85 at entry, with a) scores of at least 4 (combined frequency and severity) on at least one symptom from each cluster (intrusion, avoidance and hyperarousal); b) score of 5 or more on CAPS17 items 4 or 5 (intense psychological distress or physiological reactivity on exposure to a reminder of the traumatic event); and c) no questionable validity (QV) rating greater than 1 on any CAPS item.
• 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.
• Clinically significant impairment in social functioning due to PTSD, manifested by one or more of the following: a) 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; b) 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; c) 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
• Cohabitation with a spouse or significant other adult person who a) can confirm the symptoms and impairment from PTSD and lack of significant symptomatic remission in the past 5 years; and b) is willing to participate with the study psychiatrist in answering questions for the life functioning in PTSD scale (LFIPS) at scheduled follow-up visits; and c) is willing to 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 these.

You may not qualify if:

• 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);
• Psychosis or bipolar disorder; significant acute or ongoing risk for violence;
• Patients primarily diagnosed with DSM-IV-TR Axis I disorder other than PTSD as determined by the MINI;
• Within the 3 months prior to enrolment, subject has started a new psychotherapy program;
• 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;
• Current significant neurological conditions, including epilepsy, stroke, movement disorder; history of serious head injury with loss of consciousness
• Patients with uncontrolled medical conditions (hypertension, diabetes, infection);
• Uncontrolled chronic pain;
• Baseline Montgomery Asberg Depression Rating Scale (MADRS) of ≥ 28;
• Patients who are receiving anticoagulation therapy;
• Significant abnormality on preoperative structural brain MRI;
• ECT in the past 6 months;
• Contraindications to MRIs or the need for recurrent body MRIs;
• Immunosuppression;
• Patients who are not appropriate candidate for general anesthesia and/or DBS surgery;

Sponsors & Collaborators

• VA Greater Los Angeles Healthcare System: lead

Study Sites (1)

VA Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

RECRUITING

Related Publications (2)

• Langevin JP, De Salles AA, Kosoyan HP, Krahl SE. Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. J Psychiatr Res. 2010 Dec;44(16):1241-5. doi: 10.1016/j.jpsychires.2010.04.022. Epub 2010 May 26.

  PMID: 20537659 BACKGROUND

• Stidd DA, Vogelsang K, Krahl SE, Langevin JP, Fellous JM. Amygdala deep brain stimulation is superior to paroxetine treatment in a rat model of posttraumatic stress disorder. Brain Stimul. 2013 Nov;6(6):837-44. doi: 10.1016/j.brs.2013.05.008. Epub 2013 Jun 25.

  PMID: 23835167 BACKGROUND

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Jean-Philippe Langevin, MD

CONTACT

310 268-3463; jlangevin@mednet.ucla.edu

Ralph Koek, MD

CONTACT

800-516-4567; ralph.koek@va.gov

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 14, 2014
• First Posted: March 19, 2014
• Study Start: January 1, 2014
• Primary Completion: December 1, 2024
• Study Completion: December 31, 2025
• Last Updated: October 14, 2022

Record last verified: 2022-10

Locations

US (1)