Nerve Stimulation for Weight Loss and Diabetes

Overseen By John Williamson, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Florida

Disqualifiers: Neurological, Psychiatric, Cancer, others

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

Compensation: Varies

Number of Visits: 3

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how weight loss and diabetes improvements after bariatric surgery affect brain function and thinking. It also examines whether a non-invasive technique called transcutaneous vagal nerve stimulation (tVNS), applied 30 days after surgery, can further enhance brain function. Participants will undergo either an anterior or complete vagotomy (a surgical procedure involving the vagus nerve, commonly performed during bariatric surgery) and may receive real or sham (fake) tVNS. Suitable candidates are English-speaking individuals with a BMI over 35, who are comfortable with MRI scans and can provide a small blood sample. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research on brain function improvements following bariatric surgery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that transcutaneous vagus nerve stimulation (tVNS) is generally safe and well-tolerated. Studies have found it can reduce pain and improve symptoms in various conditions. For instance, it has been used without major side effects to treat rheumatoid arthritis and knee osteoarthritis. Additionally, researchers have studied tVNS for its potential to decrease appetite and aid in weight loss, with promising results.

Regarding surgery, vagotomy (cutting the vagus nerve) is a common component of weight-loss surgery. While all surgeries carry risks, surgeons regularly perform vagotomy, indicating it is well-understood and manageable.

In summary, past studies have shown both tVNS and vagotomy to be safe, making them reasonable options for those considering participation in related clinical trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about nerve stimulation for weight loss and diabetes because it offers a novel approach that targets the vagus nerve, which plays a crucial role in hunger and metabolism. Unlike conventional treatments such as lifestyle interventions, medications, or surgical procedures like standard bariatric surgery, this method combines transcutaneous vagus nerve stimulation (tVNS) with vagotomy to potentially enhance weight loss and improve metabolic outcomes. The combination of tVNS with surgical vagotomy could modify nerve signals that regulate appetite and glucose metabolism, offering a promising alternative that might augment the effectiveness of existing bariatric procedures. This innovative approach could provide new insights into managing obesity and diabetes more effectively.

What evidence suggests that this trial's treatments could be effective for weight loss and diabetes?

This trial will explore different combinations of treatments for weight loss and diabetes. Research has shown that transcutaneous vagus nerve stimulation (tVNS), which participants in some trial arms will receive, can help reduce appetite, support weight loss, and improve insulin handling. Studies have found that it can lead to noticeable decreases in body weight and body mass index.

For anterior vagotomy, included in certain trial arms, research suggests it can enhance the effects of weight-loss surgery by maintaining metabolic improvements and aiding weight loss. Complete vagotomy, another treatment option in this trial, has also been linked to significant weight loss and better blood sugar control in people with diabetes. These treatments aim to help with weight management and improve diabetes by altering nerve signals related to hunger and metabolism. ^{1 6 7 8 9}

Who Is on the Research Team?

Eric Porges, PhD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

The WISE-2B Brain Study is for individuals aged 20-75 with severe weight issues (BMI over 35) who are about to undergo bariatric surgery. Participants must be able to have an MRI scan, provide a blood sample, speak English, and move around on their own. People with claustrophobia, metal implants that affect MRI, neurological disorders, major psychiatric conditions or unstable medical situations like cancer cannot join.

Inclusion Criteria

My BMI was over 35 kg/m2 before surgery.

Compatible with MRI Scanning

Willing to give a small blood sample

Exclusion Criteria

MRI contraindications (claustrophobia, metal implants, waist/torso circumference)

Prior or current neurological disorder

Major psychiatric disturbance

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Surgery and Initial Assessment

Participants undergo bariatric surgery and initial cognitive and MRI assessments

1 week

1 visit (in-person)

tVNS Intervention

Participants receive non-invasive transcutaneous vagal nerve stimulation for 30 days post-surgery

4 weeks

Home-based intervention

Follow-up Assessments

Participants are assessed on cognitive and brain function at 12 weeks and 18 months post-surgery

18 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Anterior Vagotomy
• Complete Vagotomy
• tVNS

Trial Overview This study examines how brain function and thinking are affected by weight loss and diabetes improvement after bariatric surgery. It also tests if starting non-invasive transcutaneous vagal nerve stimulation (tVNS) therapy 30 days post-surgery can further improve cognitive functions. The cost of the surgery itself isn't covered by the study.

How Is the Trial Designed?

Group I: tVNS + complete vagotomy Experimental Treatment 2 Interventions

This arm will receive transcutaneous vagus nerve stimulation and a complete vagotomy during their bariatric surgery. Note a vagotomy is standard practice during bariatric surgery

Group II: tVNS + anterior vagotomy Experimental Treatment 2 Interventions

This arm will receive transcutaneous vagus nerve stimulation and an anterior vagotomy during their bariatric surgery. Note a vagotomy is standard practice during bariatric surgery.

Group III: Sham + complete vagotomy Placebo Group 1 Intervention

This arm will not receive transcutaneous vagus nerve stimulation and will receive a complete vagotomy during their bariatric surgery. Note a vagotomy is standard practice during bariatric surgery.

Group IV: Sham + anterior vagotomy Placebo Group 1 Intervention

This arm will not receive transcutaneous vagus nerve stimulation and will receive an anterior vagotomy during their bariatric surgery. Note a vagotomy is standard practice during bariatric surgery.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 24 children undergoing intermittent vagal nerve stimulation over a total of 61 patient years, 15 adverse events were reported, with 13 likely related to the device, indicating a need for careful monitoring during treatment.

Despite the occurrence of adverse events, vagal nerve stimulation was generally well tolerated, and unlike standard drug therapies, these events did not typically require stopping the treatment, although they sometimes led to unexpected surgeries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in children receiving intermittent left vagal nerve stimulation. Murphy, JV., Hornig, GW., Schallert, GS., et al.[2019]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S002604952200141X

Metabolic effects of truncal vagotomy when combined with ... We hypothesize that the addition of a surgical truncal vagotomy (TV) may improve and solidify the beneficial results of BMS on T2DM by stably decreasing EPS.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5187356/

Two-Year Outcomes of Vagal Nerve Blocking (vBloc) for ... From 12 to 18 months, the vBloc arm maintained its weight loss while the Sham arm regained 40 % of weight lost at 12 months, so that at 18 ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1155/2013/245683

Vagal Blocking Improves Glycemic Control and Elevated ... Background. An active device that downregulates abdominal vagal signalling has resulted in significant weight loss in feasibility studies.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06861790

NCT06861790 | WISE-2B Brain Study (Weight Loss ... This intervention is completed daily for one month. Procedure : Anterior Vagotomy. Participants will not be receiving bariatric surgery as an intervention of ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/21359897/

Laparoscopic adjustable gastric banding with truncal ... Published studies demonstrate clinically significant weight loss by subjects undergoing open surgical truncal vagotomy for ulcer disease and morbid obesity.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9093220/

Clinical perspectives on vagus nerve stimulation This review discusses current preclinical and clinical evidence supporting the efficacy of VNS in different diseases and highlights recent advancements.

7. withpower.com withpower.com/trial/phase-weight-loss-2-2025-6a767

Nerve Stimulation for Weight Loss and Diabetes This N/A medical study run by University of Florida is evaluating whether Anterior Vagotomy and Complete Vagotomy will have tolerable side effects ...

8. aetna.com aetna.com/cpb/medical/data/100_199/0191.html

Vagus Nerve Stimulation - Medical Clinical Policy Bulletins VNS with a miniaturized neurostimulator was safe and well-tolerated and reduced signs and symptoms of RA in patients with multidrug-refractory disease.

9. nature.com nature.com/articles/s41598-025-01964-6

Transcutaneous auricular vagus nerve stimulation inhibits ... According to the research findings, taVNS can effectively reduce appetite and weight gain, enhance insulin sensitivity, and ultimately exert a ...