Deep Brain Stimulation for Obesity

Overseen by Donald Whiting, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Waitlist Available

Sponsor: Donald M. Whiting, MD

No Placebo Group

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a new treatment for people with severe obesity who haven't had success with other methods. The treatment involves placing small devices in the brain that send electrical signals to help control eating habits. The goal is to see if this can help these patients lose weight and improve their quality of life.

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 data supports the idea that Deep Brain Stimulation for Obesity is an effective treatment?

The available research shows that Deep Brain Stimulation (DBS) for obesity has been tested in both humans and animals with some promising results. In a pilot study with humans, DBS in the lateral hypothalamic area (LHA) was found to be safe over a 2-year period, with early signs of effectiveness in managing body weight and energy use. In animal studies, DBS led to a significant and lasting decrease in food intake and weight loss in rats. However, the outcomes in humans have been mixed, with some brain targets showing disappointing results, while others, like the nucleus accumbens, showed more encouraging outcomes for weight reduction and eating behavior control. Despite these promising findings, the research is still in early stages, and more studies are needed to determine the best brain targets and strategies for using DBS to treat obesity effectively. ^{1 2 3 4 5}

What safety data is available for deep brain stimulation in treating obesity?

The safety data for deep brain stimulation (DBS) targeting the lateral hypothalamic area (LHA) in treating obesity includes a 2-year pilot study with 3 patients, showing preliminary safety results. Additionally, DBS in the hypothalamus has been investigated for its effects on related neural systems, which could lead to adverse side effects. The procedure is considered to have a well-established safety profile, but surgical risks, including some mortality cases, have been reported when targeting certain hypothalamic areas. Overall, DBS is seen as a feasible and potentially effective treatment for obesity, with ongoing research to improve safety and efficacy. ^{1 2 6 7 8}

Is DBS of the LHA a promising treatment for obesity?

Yes, DBS of the LHA is a promising treatment for obesity. It has shown potential in reducing body weight and controlling eating behavior by influencing brain areas related to hunger and energy use. Early studies in both humans and animals suggest it could be a safe and effective way to help manage obesity. ^{1 2 3 4 5}

Research Team

Donald Whiting, MD

Principal Investigator

Allegheny Health Network

Eligibility Criteria

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.

Treatment Details

Interventions

• DBS of the LHA (Device)

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.

Participant Groups

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

Findings from Research

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]

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) 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) 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) 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) 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) 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]

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]

References

1. United States 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. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for treatment of obesity in rats. [2007]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Deep Brain Stimulation for Obesity: A Review and Future Directions. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Deep brain stimulation for obesity: past, present, and future targets. [2015]

5. United States 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. [2021]

6. Switzerland 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. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Rationale for hypothalamus-deep brain stimulation in food intake disorders and obesity. [2015]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Effectiveness of Deep Brain Stimulation in Reducing Body Mass Index and Weight: A Systematic Review. [2022]