Deep Brain Stimulation for PTSD

Overseen By Ralph Koek, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: VA Greater Los Angeles Healthcare System

Must not be taking: Anticoagulants, Psychotropic herbs

Disqualifiers: Suicide attempt, Psychosis, Bipolar, Alcohol use, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

6 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to assist veterans with PTSD, particularly those unresponsive to current treatments. The treatment, Deep Brain Stimulation (DBS) of the Basolateral Nucleus of the Amygdala, involves placing tiny electrodes in the brain to calm overactive areas causing PTSD symptoms. The trial includes two groups, with each group starting the treatment at different times after the procedure. Veterans who have had PTSD for at least five years, have not responded to various medications and therapies, and face significant daily challenges due to PTSD may be suitable candidates for this trial. As an unphased trial, this study provides veterans with a unique opportunity to explore innovative treatment options that might not be available elsewhere.

Will I have to stop taking my current medications?

Participants must be stable on their current psychotropic medications for 2 months before the trial and cannot increase dosages or add new medications for the first 6 months, unless medically necessary.

What prior data suggests that this deep brain stimulation technique is safe for treating PTSD?

Research has shown that deep brain stimulation (DBS) of the amygdala has been studied as a treatment for PTSD. In one study, two combat veterans with PTSD that didn't improve with other treatments received high-frequency DBS in the amygdala. Electrodes were placed in their brains to help manage their symptoms. The study found no major safety issues for these patients. However, like any medical procedure, potential risks exist. Considering these risks and possible benefits is important when deciding to join a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about deep brain stimulation (DBS) for PTSD because it offers a novel approach compared to standard treatments like therapy and medication. Unlike the usual methods that focus on talk therapy or altering brain chemistry with drugs, DBS directly targets the brain's basolateral nucleus of the amygdala, which is involved in emotional responses. This technique has the potential to provide quicker and more precise relief from PTSD symptoms by modulating brain activity at its source. Moreover, it could offer an option for those who haven't found success with existing treatments, bringing new hope to patients with treatment-resistant PTSD.

What evidence suggests that deep brain stimulation might be an effective treatment for PTSD?

Research has shown that deep brain stimulation (DBS) of the amygdala might help reduce PTSD symptoms. Previous studies found that DBS can calm unusual brain activity linked to PTSD. For instance, two veterans with severe PTSD, unresponsive to other treatments, experienced improvement after receiving amygdala DBS for long periods—9 and 5.5 years—without serious side effects like seizures. Additionally, animal studies have demonstrated that DBS of the amygdala reduces PTSD symptoms in rats. This trial will explore two different approaches: DBS of the amygdala starting at 30 days post-operatively and at 90 days post-operatively. These findings suggest that targeting the amygdala with DBS could offer a new option for people who haven't found success with other PTSD treatments. ^{2 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for male veterans aged 25-70 with chronic, treatment-resistant PTSD from combat. They must have a stable medical condition and psychotropic medication use, cohabitate with someone who can report on their symptoms, and have tried multiple treatments without success. Excluded are those with certain implants, recent suicide attempts or substance abuse issues, significant cognitive impairments or other major psychiatric disorders.

Inclusion Criteria

Able to give informed consent in accordance with institutional policies and participate in the 2-year follow-up, involving assessments and stimulator adjustments

Confirmation of PTSD as the primary psychiatric diagnosis by the study psychiatrist via clinical interview and CAPS

I have tried specific medications for at least 3 months.

Exclusion Criteria

Current pursuit of new or increased disability compensation for PTSD

Patients suffering from a condition associated with a significant cognitive impairment

Significant abnormality on preoperative structural brain MRI

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery

Placement of intracranial electrodes for deep brain stimulation

1 week

Post-operative Recovery

Participants recover from surgery before starting stimulation

4 weeks

DBS Treatment

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

30 days

DBS Treatment

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

90 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The study tests Deep Brain Stimulation (DBS) of the Basolateral Nucleus of the Amygdala using Medtronic Activa PC DBS to alleviate PTSD symptoms. Participants will undergo electrode implantation in the brain and receive follow-up assessments and stimulator adjustments over two years.

How Is the Trial Designed?

Group I: DBS of the Amygdala-90 days Experimental Treatment 2 Interventions

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

Group II: DBS of the Amygdala-30 days Experimental Treatment 2 Interventions

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

DBS of the Basolateral Nucleus of the Amygdala is already approved in United States, European Union for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Obsessive-compulsive disorder
• Clinical trials for PTSD (not FDA-approved)

Approved in European Union as Deep Brain Stimulation for:

• Parkinson's disease
• Essential tremor
• Obsessive-compulsive disorder
• Clinical trials for various psychiatric conditions including PTSD (not EU-approved for PTSD)

Who Is Running the Clinical Trial?

VA Greater Los Angeles Healthcare System

Lead Sponsor

Trials

53

Recruited

8,700+

Published Research Related to This Trial

Deep brain stimulation (DBS) has been explored as a treatment for PTSD, particularly in combat veterans, with promising results observed in animal models targeting specific brain areas like the medial prefrontal cortex and amygdala.

In clinical reports involving 3 patients, all showed varying degrees of improvement after receiving DBS, indicating potential efficacy, but the treatment remains investigational due to ethical concerns and challenges in recruitment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Post-Traumatic Stress Disorder: A Review of the Experimental and Clinical Literature. Meeres, J., Hariz, M.[2022]

Deep brain stimulation (DBS) electrodes can be effectively implanted in the basolateral nucleus of the amygdala using a transfrontal approach, which may help treat severe post-traumatic stress disorder (PTSD).

Intra-operative neurostimulation elicited pleasant memories, and post-operative EEG monitoring showed improved sleep patterns, suggesting that DBS may reduce anxiety and enhance emotional regulation in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation of the Basolateral Amygdala: Targeting Technique and Electrodiagnostic Findings. Langevin, JP., Chen, JW., Koek, RJ., et al.[2020]

In individuals with PTSD, there is greater activation of the basolateral amygdala (BLA) compared to the centromedial amygdala (CMA) during the successful encoding of negative emotional scenes, indicating a specific role of the BLA in processing threatening information.

This increased BLA activation during memory tasks was found to independently predict PTSD status, suggesting that targeting this subregion could be important for understanding and potentially treating PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder. Patel, R., Girard, TA., Pukay-Martin, N., et al.[2019]

This study outlines a Phase I pilot trial investigating the safety and efficacy of deep brain stimulation (DBS) targeting the basolateral amygdala in six combat veterans with severe, treatment-resistant PTSD, with a primary goal of achieving a 30% reduction in PTSD symptoms as measured by the Clinician Administered PTSD Scale (CAPS).

The trial design includes rigorous safety monitoring and assessments of psychiatric and neurological symptoms, aiming to gather valuable data that could inform future studies on DBS for PTSD in both veterans and non-veterans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the basolateral amygdala for treatment-refractory combat post-traumatic stress disorder (PTSD): study protocol for a pilot randomized controlled trial with blinded, staggered onset of stimulation. Koek, RJ., Langevin, JP., Krahl, SE., et al.[2023]

Deep brain stimulation (DBS) of the amygdala significantly reduced PTSD-like behaviors in rats, as evidenced by treated rats spending 13 times less time burying a stress-inducing object compared to control rats.

The treated rats also showed a marked increase in exploratory behavior, spending 18 times more time interacting with the object, suggesting that DBS may effectively normalize PTSD symptoms and offers a promising new treatment strategy for patients with treatment-resistant PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation of the amygdala alleviates post-traumatic stress disorder symptoms in a rat model. Langevin, JP., De Salles, AA., Kosoyan, HP., et al.[2022]

A patient with drug-resistant epilepsy experienced significant psychiatric side effects, including irritability and paranoia, after receiving deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS).

Even after stopping the stimulation, the psychiatric side effects persisted long-term, suggesting that ANT-DBS may cause lasting changes in thalamic neuronal networks responsible for these effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anterior thalamic deep brain stimulation in epilepsy and persistent psychiatric side effects following discontinuation. Doležalová, I., Kunst, J., Kojan, M., et al.[2020]

The study investigated how the amygdala's basolateral nuclei influence the vestibular sensory system in rabbits, suggesting a modulatory role.

It discusses the mechanism by which the amygdala affects the activity of neurons in the Deiters nucleus, which is important for balance and spatial orientation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of stimulation of the amygdala basolateral nuclei on the neuron activity of Deiters vestibular nuclei in rabbits]. Minasian, SM., Baklavadzhian, OG., Adamian, TsI., et al.[2016]

The basolateral nucleus of the amygdala is identified as a key area exhibiting sexual dimorphism, influencing sexual behavior and the regulation of reproductive hormone secretion.

This nucleus integrates sensory information and plays a significant role in emotional responses and memory, which may lead to different behavioral reactions to stress between sexes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[THE BASOLATERAL NUCLEUS IN THE SYSTEM OF REPRODUCTIVE CENTERS OF THE AMYGDALA]. Akhmadeyev, AV., Galiyeva, LF., Kalimullina, LB.[2015]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4168122/

Deep brain stimulation of the basolateral amygdala for ... The present paper discusses the rationale and methodology for experimental use of deep brain stimulation (DBS) for treatment-refractory combat post-traumatic ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0022395624002644

Deep brain stimulation of the amygdala for treatment ... Two veterans with severe combat TR-PTSD received amygdala DBS for 9 and 5.5 years. Stimulation resulted in no seizures, neuropsychological or psychiatric ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01658748

A Pilot Study of Deep Brain Stimulation of the Amygdala for ... 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 ...

4. ucla.clinicaltrials.researcherprofiles.org ucla.clinicaltrials.researcherprofiles.org/trial/NCT02091843

UCLA Post-Traumatic Stress Disorder Trial → Deep Brain ... Although the current therapy is effective, a percentage of patients will fail to improve and will develop chronic treatment-resistant PTSD.

5. mdpi.com mdpi.com/2076-3425/6/3/28

Deep Brain Stimulation of the Basolateral Amygdala It could prove to be an effective neuromodulation target in the treatment of psychiatric conditions characterized by failure of extinction. We aim to describe ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11419692/

Deep brain stimulation of the amygdala for treatment-resistant ... Here, we report long-term data on two TR-PTSD participants from an investigation utilizing high-frequency amygdala DBS. The two combat veterans were implanted ...

7. withpower.com withpower.com/trial/phase-stress-disorders-post-traumatic-2014-d66a4

Deep Brain Stimulation for PTSD Trial Overview The study tests Deep Brain Stimulation (DBS) of the Basolateral Nucleus of the Amygdala using Medtronic Activa PC DBS to alleviate PTSD symptoms.