Deep Brain Stimulation for Schizophrenia

Overseen By Hila Abush Segev, Ph.D

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Bradley Lega

Must be taking: Antipsychotics

Must not be taking: Antidepressants, Amphetamines

Disqualifiers: Substance use disorder, Suicidal risk, Seizure disorder, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the safety and effectiveness of deep brain stimulation (DBS) for individuals with schizophrenia unresponsive to traditional treatments. Researchers will map participants' brain activity to create personalized DBS settings and determine if it can reduce psychotic symptoms. The study will also develop methods to adjust brain stimulation based on real-time brain activity. Individuals with persistent, challenging schizophrenia symptoms who haven't found lasting relief from at least two different medications may be suitable candidates for this trial. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for schizophrenia.

Will I have to stop taking my current medications?

The trial requires participants to have a stable antipsychotic medication regimen for the month before surgery, so you may need to maintain your current antipsychotic medications. However, if you are taking antidepressants or medications that interact with ketamine, you may need to stop those. The protocol does not specify a washout period for other medications, so it's best to discuss your specific situation with the trial team.

What prior data suggests that this deep brain stimulation is safe for schizophrenia?

Research shows that deep brain stimulation (DBS) is being explored as a treatment for individuals with schizophrenia who do not respond to medication. Studies have found that DBS can aid in managing other difficult-to-treat conditions and can enhance quality of life.

Regarding safety, early trials suggest that DBS is generally well-tolerated. Some side effects occur, but they are usually mild. For instance, some individuals might experience temporary discomfort or mild effects after the procedure. However, these trials have not widely reported any unexpected severe side effects. This suggests that DBS could be a safe option for those with schizophrenia when other treatments have failed.

It is important to discuss any concerns with a healthcare provider before considering participation in a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Deep Brain Stimulation (DBS) is unique for schizophrenia treatment because it targets the brain directly by using electrical impulses to modulate neural activity. Unlike standard treatments like antipsychotic medications, which primarily target chemical imbalances, DBS offers a new mechanism by directly altering brain circuits associated with symptoms. Researchers are excited about DBS because it has the potential to provide relief for patients who don't respond well to traditional therapies, and it might offer a more precise, personalized approach to managing schizophrenia symptoms.

What evidence suggests that Deep Brain Stimulation is effective for schizophrenia?

Research has shown that deep brain stimulation (DBS) can help people with schizophrenia who haven't responded to other treatments. This trial will assign participants to different arms to evaluate the effects of DBS. In one study, most patients experienced significant symptom improvement after receiving DBS. Another study found that patients remained stable and even improved a year after treatment. DBS sends electrical signals to specific brain areas involved in schizophrenia, aiming to restore normal brain function. While responses may vary, these findings suggest that DBS could be promising for those who haven't found relief with other treatments. ^{2 3 6 7 8}

Who Is on the Research Team?

Bradley Lega, MD

Principal Investigator

UT Southwestern Medical Center

David McDonagh, M.D.

Principal Investigator

UT Southwestern Medical Center

Nader Pouratian

Principal Investigator

UT Southwestern Medical Center

Carol A Tamminga, MD

Principal Investigator

UT Southwestern Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with treatment-refractory schizophrenia, meaning their condition hasn't improved after trying other treatments. Participants will undergo a procedure to implant the Infinity™ DBS system and must be comfortable with intracranial mapping and potential ketamine administration.

Inclusion Criteria

PANSS score greater than or equal to 90 on two separate assessments over a 1-month period

I am between 22 and 70 years old and not pregnant.

My antipsychotic medication has not changed in the last month.

Exclusion Criteria

Any condition that makes the participant a poor candidate

I cannot have surgery due to a medical condition like an infection.

I am a woman able to have children and am not using strong birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Period

Participants receive open-label deep brain stimulation to optimize settings

8 weeks

Randomized Discontinuation Period

Participants undergo randomized discontinuation with alternating 'ON' and 'OFF' DBS periods

16 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Deep Brain Stimulation

Trial Overview The study tests the safety and effectiveness of Abbott Laboratories' Infinity™ deep brain stimulation system in managing schizophrenia symptoms. It involves brain mapping, machine learning techniques to identify non-psychotic states, and personalized stimulation protocols.

How Is the Trial Designed?

Group I: Randomized Discontinuation Period: OFF then ON DBS Experimental Treatment 1 Intervention

Subjects randomized to this arm are initially "OFF" DBS after the open label period then gradually decreased in their optimized setting's amplitude for 8 weeks and then "ON" DBS for 8 weeks.

Group II: Experimental: Randomized Discontinuation Period: ON then OFF DBS Experimental Treatment 1 Intervention

Subjects randomized to this arm are initially "ON" DBS with optimized stimulation settings for 8 weeks after the open label period and then "OFF" DBS with gradually decreasing amplitude for 8 weeks.

Deep Brain Stimulation is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain
• Stroke-related motor deficits (under investigation)

Approved in European Union as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Approved in Canada as Deep Brain Stimulation for:

• Essential tremor
• Parkinson's disease
• Dystonia
• Obsessive-compulsive disorder
• Epilepsy
• Chronic pain

Who Is Running the Clinical Trial?

Bradley Lega

Lead Sponsor

Trials

1

Recruited

10+

Published Research Related to This Trial

Deep brain stimulation (DBS) is being explored as a potential treatment for schizophrenia (SZ), a condition that currently has significant unmet needs due to issues like relapse and ineffective treatments for negative and cognitive symptoms.

Research suggests that SZ may be a circuit disorder, and DBS could help by modulating striatal dysregulation, with ongoing clinical trials assessing its efficacy and ethical considerations for patients with severe symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches to neuromodulation for schizophrenia. Gault, JM., Davis, R., Cascella, NG., et al.[2022]

Deep brain stimulation (DBS) targeting the nucleus accumbens (NAcc) and subgenual anterior cingulate cortex (subgenual ACC) shows potential therapeutic effects in treatment-resistant schizophrenia, with 58% improvement in PANSS scores for NAcc and 68% for subgenual ACC among patients who met improvement criteria.

While physical side effects were rare, two patients experienced persistent psychiatric adverse effects, highlighting the need for larger trials to assess the safety and efficacy of DBS in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation in treatment resistant schizophrenia: A pilot randomized cross-over clinical trial. Corripio, I., Roldán, A., Sarró, S., et al.[2021]

Deep brain stimulation (DBS) has shown promise in treating treatment-resistant schizophrenia, with four out of seven patients meeting symptomatic response criteria after stimulation in either the subgenual anterior cingulate cortex or the nucleus accumbens.

DBS was associated with significant changes in glucose metabolism in various brain regions, suggesting that it may improve symptoms by modulating activity in the cortico-basal-thalamic-cortical circuit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain metabolic changes in patients with treatment resistant schizophrenia treated with deep brain stimulation: A series of cases. Roldán, A., Portella, MJ., Sampedro, F., et al.[2021]

In a comparison of surgical outcomes, patients with schizophrenia/schizoaffective disorder (SZ/SAD) showed lower postsurgical mortality rates (1.01-4.11% lower) than those with Parkinson's disease (PD), suggesting that surgical risks may not be as high as previously thought for DBS in SZ/SAD.

While morbidity was slightly higher in SZ/SAD patients (1.91-2.73% higher), there was no increase in serious complications like hemorrhages or infections, indicating that DBS could be a viable option for these patients under careful selection criteria.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postsurgical morbidity and mortality favorably informs deep brain stimulation for new indications including schizophrenia and schizoaffective disorder. Gault, JM., Hosokawa, P., Kramer, D., et al.[2023]

Deep brain stimulation (DBS) of the habenula has shown promise as a safe and effective treatment for severe, chronic, and treatment-resistant schizophrenia in two young adult male patients, with initial improvements in symptoms observed within the first 6 months after surgery.

While one patient maintained clinical benefits at the 12-month follow-up, the other experienced a worsening of symptoms, highlighting that while DBS may be beneficial for some, it does not guarantee long-term success for all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Habenula deep brain stimulation for intractable schizophrenia: a pilot study. Wang, Y., Zhang, C., Zhang, Y., et al.[2021]

A systematic review of 96 studies found that the most common complications from Deep Brain Stimulation (DBS) procedures include infections (5.12% of patients) and lead migration (1.60%), highlighting the importance of monitoring for these issues post-surgery.

Patients with conditions like dystonia and off-label indications such as Tourette's syndrome are at a higher risk for hardware-related complications, suggesting that these patients should receive thorough pre-surgical counseling and close follow-up care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic review of hardware-related complications of Deep Brain Stimulation: Do new indications pose an increased risk? Jitkritsadakul, O., Bhidayasiri, R., Kalia, SK., et al.[2022]

In a one-year study involving four treatment-resistant patients with schizophrenia and bipolar disorder, deep brain stimulation (DBS) led to significant clinical improvements, including reduced scores on the Clinical Global Impression and Hamilton Depression Rating Scale.

DBS was found to be safe, with no side effects or cognitive changes reported, and allowed three patients to discontinue maintenance electroconvulsive therapy, suggesting it may be a viable treatment option for complex psychiatric disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation and digital monitoring for patients with treatment-resistant schizophrenia and bipolar disorder: A case series. Bioque, M., Rumià, J., Roldán, P., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12536682/

Effectiveness of deep brain stimulation in alleviating ... The study involved 13 patients undergoing stimulation for an average of 26.61 ± 12.36 months (see Table 1). Twelve patients showed improvement ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6953640/

Deep brain stimulation in treatment resistant schizophrenia Of the remaining 7 patients, 2/3 with NAcc and 2/4 with subgenual ACC electrode placements met the symptomatic improvement criteria (58% and 86% ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2667049625000274

Review Deep brain stimulation in neuropsychiatric disorders DBS proves effective in refractory neuropsychiatric disorders, modulating specific symptoms and improving quality of life. Methodological ...

4. hopkinsmedicine.org hopkinsmedicine.org/news/newsroom/news-releases/2021/06/deep-brain-stimulation-for-treating-schizophrenia--johns-hopkins-medicine-experts-say-it-works

Deep Brain Stimulation for Treating Schizophrenia After one year of deep brain stimulation, the patient remains stably improved, with no significant complications or adverse reactions related to ...

5. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(24)00625-4/fulltext

Efficacy of brain stimulation therapies across psychiatric, ... For dichotomous outcomes, the majority of studies showed significant treatment response or rTMS (OR range: 3.16–5.12) and tDCS (OR range: 1.63–4.17), as well as ...

6. frontiersin.org frontiersin.org/journals/surgery/articles/10.3389/fsurg.2023.958452/full

Postsurgical morbidity and mortality favorably informs deep ... Background: Deep brain stimulation (DBS) shows promise for new indications like treatment-refractory schizophrenia in early clinical trials.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12362889/

Ethical considerations of deep brain stimulation for ... Audience approval of DBS was similar for the PD (30%), SZ (52%) and the OCD case with psychosis (56%), but there was a higher rate of approval ( ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT02377505

Deep Brain Stimulation in Treatment Resistant Schizophrenia This study aims at assessing efficacy and safety of Deep Brain Stimulation (DBS) for treatment of patients with treatment resistant schizophrenia, ...