Deep Brain Stimulation for Obesity

Overseen By George Eid, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Donald M. Whiting, MD

Must not be taking: Anticoagulants, Weight-loss drugs

Disqualifiers: Psychiatric conditions, Substance abuse, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 17

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat chronic obesity that has not improved with other treatments like gastric bypass surgery. Researchers are testing whether deep brain stimulation (DBS), which uses electrical impulses in specific brain areas, can help manage weight. Ideal participants are those who have undergone gastric bypass but remain significantly overweight and have maintained a stable weight for the past year. The study aims to determine if DBS, specifically targeting the lateral hypothalamic area (LHA), is safe and effective for those who have not found success with other options. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could lead to new treatment options for obesity.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot use weight-loss prescription drugs or over-the-counter weight loss preparations, and you must discontinue anticoagulant medications during the perioperative period.

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

Research has shown that deep brain stimulation (DBS) in the lateral hypothalamic area (LHA) can be safely used in individuals with severe obesity. One study on individuals with difficult-to-treat obesity found that this treatment was well-tolerated, with no major safety issues. Another series of cases involving patients with obesity due to Prader-Willi syndrome also supported the safety of LHA DBS, showing no significant negative effects in participants.

Overall, early studies suggest that LHA DBS is generally safe and might aid weight loss in some cases. However, these findings are based on small groups, so more research is needed to fully understand the treatment's safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Deep Brain Stimulation (DBS) for obesity because it offers a novel way to tackle the condition by directly targeting the brain's lateral hypothalamic area (LHA), which plays a key role in hunger and energy balance. Unlike traditional treatments like lifestyle changes, medications, or bariatric surgery, DBS uses electrical impulses to modulate brain activity, potentially leading to more effective and lasting weight loss. This innovative approach could offer hope for individuals who haven't found success with other options, as it directly influences the neural circuits involved in appetite control and metabolism.

What evidence suggests that DBS of the LHA might be an effective treatment for chronic refractory obesity?

Research suggests that stimulating the lateral hypothalamic area (LHA) of the brain might help treat obesity unresponsive to other methods. In previous studies, participants who received this treatment, known as deep brain stimulation (DBS), showed a small reduction in body mass index (BMI), losing about 3.97 BMI points on average. Although this change is modest, it suggests that DBS might benefit some individuals with severe obesity. However, not all studies agree, and some indicate it might not be effective for everyone. Overall, the results are mixed, but there is hope that LHA DBS, which participants in this trial will receive, could offer another option for those dealing with chronic obesity. ^{1 4 6 7 8}

Who Is on the Research Team?

Donald Whiting, MD

Principal Investigator

Allegheny Health Network

Are You a Good Fit for This Trial?

This trial is for adults aged 22-65 with severe obesity (BMI ≥ 50 kg/m2) who have been stable in weight for a year and whose bariatric surgery failed. They must not have any neuropsychiatric issues that could affect participation, no history of seizures or hemorrhagic stroke, and should not be at high risk of infection.

Inclusion Criteria

My weight has been stable, within 3 kg, for the last year.

My weight loss surgery didn't work, and there's no surgical fix.

Platelet count >125,000 per cubic mm

Exclusion Criteria

I am currently using prescription or over-the-counter weight loss drugs.

I am currently diagnosed with a major depressive episode or my depression score is 17 or higher.

You have had a Vagus Nerve Stimulation (VNS) device implanted in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

DBS Implantation

Subjects undergo a two-part DBS implantation procedure for placement of DBS electrodes in the LHA

1-2 weeks

2 visits (in-person)

Treatment

Participants receive bilateral DBS of the LHA and undergo RMR testing to determine optimal settings for stimulation

12 months

Regular follow-up visits as per outcome measure timeframes

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Periodic assessments at 15, 18, 20, and 24 months post-surgery

What Are the Treatments Tested in This Trial?

Interventions

• DBS of the LHA

Trial Overview The study tests the safety and effectiveness of deep brain stimulation (DBS) on the lateral hypothalamic area (LHA) in patients with chronic refractory obesity who haven't responded to other treatments including gastric bypass surgery.

How Is the Trial Designed?

Group I: LHA DBS Experimental Treatment 1 Intervention

Subjects will receive bilateral DBS of the LHA

Who Is Running the Clinical Trial?

Donald M. Whiting, MD

Lead Sponsor

Trials

1

donald whiting

Lead Sponsor

Trials

1

Boston Scientific Corporation

Industry Sponsor

Trials

758

Recruited

867,000+

Michael F. Mahoney

Boston Scientific Corporation

Chief Executive Officer since 2016

MBA from Wake Forest University, BBA in Finance from the University of Iowa

Kenneth Stein

Boston Scientific Corporation

Chief Medical Officer since 2020

MD from Harvard Medical School, MMSc in Clinical Investigation from Harvard-MIT Division of Health Sciences and Technology

Published Research Related to This Trial

In a study involving 16 rats on a high-fat diet, continuous electrical stimulation of the lateral hypothalamic nucleus (LH) led to significant and sustained weight loss, with the stimulated group losing an average of 2.3% of their body weight compared to a 13.8% gain in the control group.

The results suggest that targeting the LH with deep brain stimulation could be a promising approach for controlling appetite and managing obesity, as the stimulated rats did not regain weight while the control group did.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment of obesity in rats. Sani, S., Jobe, K., Smith, A., et al.[2007]

Deep brain stimulation (DBS) has shown potential for weight loss in patients with refractory obesity, with an average decrease in body mass index (BMI) from 46.7 to 42.8 after treatment, particularly benefiting those with primary obesity.

While DBS can lead to weight loss, it is associated with moderate side effects in 33% of patients, including manic symptoms and seizures, highlighting the need for further research to assess long-term safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of Deep Brain Stimulation in Reducing Body Mass Index and Weight: A Systematic Review. Contreras López, WO., Navarro, PA., Crispín, S.[2022]

Deep brain stimulation (DBS) in the ventral tuberal hypothalamus (VTH) of Göttingen minipigs showed safety concerns, as it led to increased heart rate and transient aggressive behavior, indicating potential adverse effects.

PET scans revealed that VTH DBS increased cerebral blood flow and altered mean transit time, suggesting that the stimulation affects related brain networks, warranting caution and further research before human application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypothalamic deep brain stimulation influences autonomic and limbic circuitry involved in the regulation of aggression and cardiocerebrovascular control in the Göttingen minipig. Ettrup, KS., Sørensen, JC., Rodell, A., et al.[2014]

Deep brain stimulation (DBS) in the lateral hypothalamic area of obese rats led to a significant reduction in weight gain and food intake compared to control rats, indicating its potential efficacy in managing obesity.

DBS altered glucose metabolism in key brain regions related to food intake and reward, suggesting it may help normalize impaired brain functions associated with obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response to deep brain stimulation in the lateral hypothalamic area in a rat model of obesity: in vivo assessment of brain glucose metabolism. Soto-Montenegro, ML., Pascau, J., Desco, M.[2021]

Deep brain stimulation (DBS) shows preliminary evidence of safety and tolerability for treating obesity, particularly targeting the nucleus accumbens, which has shown more promising outcomes for weight reduction and eating behavior control compared to other hypothalamic targets.

Despite some encouraging results, the small number of cases and mixed outcomes highlight the need for further research to identify optimal brain targets and develop advanced DBS technologies, while also noting a serious adverse event (suicide) that occurred during the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Obesity: A Review and Future Directions. Formolo, DA., Gaspar, JM., Melo, HM., et al.[2020]

Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) is safe for humans with intractable obesity, as no serious adverse effects were reported after an average follow-up of 35 months in a pilot study of 3 patients.

While standard DBS settings did not show significant weight loss, specific stimulation settings that increased resting metabolic rate indicated promising trends for weight loss, suggesting potential for this treatment as an antiobesity strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lateral hypothalamic area deep brain stimulation for refractory obesity: a pilot study with preliminary data on safety, body weight, and energy metabolism. Whiting, DM., Tomycz, ND., Bailes, J., et al.[2021]

Deep brain stimulation (DBS) has shown promising preliminary results in both animal and human studies for treating obesity, suggesting it could effectively influence both caloric intake and energy expenditure.

Current research is exploring various brain targets and nontraditional stimulation parameters to enhance the effectiveness of DBS in obesity treatment, highlighting the potential for innovative approaches in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for obesity: past, present, and future targets. Dupré, DA., Tomycz, N., Oh, MY., et al.[2015]

Deep brain stimulation (DBS) targeting the hypothalamus shows promise for treating obesity by modulating appetite and enhancing metabolic rate, with a favorable safety profile and the ability to adjust or reverse the treatment.

While DBS has been effective in managing chronic cluster headaches, caution is needed due to potential surgical risks, particularly when targeting the posterior hypothalamus, highlighting the need for improved surgical techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale for hypothalamus-deep brain stimulation in food intake disorders and obesity. Torres, N., Chabardès, S., Benabid, AL.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/23560573/

Lateral hypothalamic area deep brain stimulation for refractory ... Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity.

2. nature.com nature.com/articles/s41398-025-03478-1

Impacts on memory, neuroplasticity and brain metabolism ... In conclusion, our results do not support continuous LH-DBS as an effective treatment to reduce body weight in cases of obesity with genetic ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01933113

Deep Brain Stimulation Effects on Weight Change and ... This study focuses on lateral hypothalamic area (LHA) deep brain stimulation (DBS) for severe obesity. In a previous pilot study, three subjects were implanted ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1878875018322940

Deep Brain Stimulation of the Hypothalamus Leads to ... For patients with obesity, DBS was most common in the lateral hypothalamus followed by the nucleus accumbens, resulting in a small decrease in BMI by 3.97 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5666570/

Lateral hypothalamic area deep brain stimulation for ... Deep brain stimulation (DBS) of the lateral hypothalamic area (LHA) has been suggested as a potential treatment for intractable obesity.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6324383/

Assessment of Safety and Outcome of Lateral ... This study of a case series of 4 patients investigates the safety and efficacy of deep brain stimulation for obesity associated with Prader-Willi syndrome.

7. sciencedirect.com sciencedirect.com/science/article/pii/S2405844023016183

Could deep brain stimulation be a possible solution for ... In the patient with CP, NAcc-DBS was associated with a decrease in BMI (−8.7%) and a subjective increase in mental health, energy and willingness to act, and no ...

8. researchdiscovery.drexel.edu researchdiscovery.drexel.edu/esploro/outputs/journalArticle/Lateral-hypothalamic-area-deep-brain-stimulation/991021448161604721?institution=01DRXU_INST

Lateral hypothalamic area deep brain stimulation for refractory ... Conclusions. Deep brain stimulation of the LHA may be applied safely to humans with intractable obesity. Early evidence for some weight loss under metabolically ...