Vagus Nerve Stimulation for Anorexia

Overseen By Tom Hildebrandt, PsyD

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Pregnancy, GI disturbance, Schizophrenia, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 4 weeks

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment Vagus Nerve Stimulation for Anorexia?

Research suggests that neuromodulation techniques, like vagus nerve stimulation, may help manage severe anorexia nervosa by targeting brain areas involved in the condition. While direct evidence for vagus nerve stimulation in anorexia is limited, similar treatments have shown potential in reducing symptoms by affecting brain activity. ^{1 2 3 4 5}

Is transcutaneous auricular vagus nerve stimulation (taVNS) safe for humans?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe for humans, with mild and temporary side effects like ear pain, headache, and tingling. Studies show no significant risk of severe adverse events compared to control treatments. ^{6 7 8 9 10}

How is the treatment taVNS different from other treatments for anorexia?

taVNS is unique because it is a non-invasive treatment that uses low-intensity electrical currents applied to the ear to stimulate the vagus nerve, which is involved in important body functions. Unlike other treatments, it does not require surgery and is portable, making it a safe and cost-effective option for managing symptoms of anorexia and related disorders. ^{8 11 12 13 14}

What is the purpose of this trial?

This trial tests a device that sends electrical pulses to a nerve in the ear to help adolescents with eating disorders. The goal is to see if it can improve their eating behaviors by controlling hunger and fullness. Electrical stimulation of this nerve has been used in other treatments and has shown effects on weight.

Research Team

Tom Hildebrandt

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for English-speaking teens aged 14-17 with low weight eating disorders, who are in a refeeding program and need to gain at least 8 lbs. It's not for those pregnant, with recent GI surgery, acute suicide risk, swallowing disorders, schizophrenia or bipolar disorder, certain device implants (like pacemakers), allergies to specific shake ingredients, substance misuse issues or diagnosed GI disturbances.

Inclusion Criteria

I am between 14 and 17 years old.

I am currently in a program for eating disorders, focusing on refeeding.

Needing to gain at least 8 lbs during the refeeding period

Exclusion Criteria

Pregnancy

Acute suicide risk/active suicidal ideation determined with the C-SSRS. 'Yes' to questions 1 or 2 in the Suicidal Ideation section or 'Yes' to any question in the Suicidal Behavior section will be exclusionary

Allergies to the ingredients in the shake provided

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive either vagal nerve stimulation or sham stimulation for 4 weeks

4 weeks

3 clinic check-ins per week, 4 weekly study visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person)

Treatment Details

Interventions

• Sham
• taVNS

Trial Overview The study tests if non-invasive vagus nerve stimulation (taVNS) before meals can improve satisfaction and calorie intake while reducing fullness feelings and anxiety compared to sham (fake) stimulation. It also measures gastric functions like rhythm and motility over four weeks.

Participant Groups

Group I: Vagal Nerve Stimulation (taVNS) Experimental Treatment 1 Intervention

taVNS stimulation administered during intervention

Group II: Sham Stimulation (Sham) Placebo Group 1 Intervention

Sham stimulation administered during intervention

taVNS is already approved in United States, European Union for the following indications:

Approved in United States as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression
• Obesity

Approved in European Union as Transcutaneous Auricular Vagus Nerve Stimulation for:

• Epilepsy
• Depression

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

In a study involving 14 patients with anorexia nervosa and 12 healthy controls, it was found that anxiety negatively affects the autonomic nervous system (ANS) of patients with anorexia.

The duration of the illness combined with the patient's body mass index (BMI) was significantly associated with changes in the ANS, indicating that sustained extreme weight loss has a major impact on autonomic function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical and psychological factors influencing heart rate variability in anorexia nervosa. Wu, Y., Nozaki, T., Inamitsu, T., et al.[2019]

Research on anorexia nervosa (AN) has evolved from focusing on psychological factors to exploring the role of neurotransmitters and the hypothalamus in its symptoms.

No single treatment has proven effective for all AN patients, and while diet, psychotherapy, and medications can help some individuals, the underlying causes and optimal treatments remain unclear after extensive research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychological aspects of anorexia nervosa. Murray, JB.[2004]

Electrical stimulation of the lateral hypothalamus in rats did not significantly improve food intake or locomotor activity, suggesting limited therapeutic effects for treating anorexia nervosa symptoms.

The study indicates that high-frequency electrical stimulation may not be an effective treatment for anorexia nervosa, as the results did not show major symptom relief in the tested model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electrical stimulation in the lateral hypothalamus in rats in the activity-based anorexia model. Welkenhuysen, M., Van Kuyck, K., Das, J., et al.[2008]

Neurosurgical interventions, particularly stereotactic ablation and deep brain stimulation (DBS), show promising evidence for effectively treating severe and enduring anorexia nervosa (AN) based on a systematic review of 20 trials.

In contrast, neuromodulatory treatments like repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have shown only modest and mixed results, indicating that more research is needed to establish their efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurosurgery and neuromodulation for anorexia nervosa in the 21st century: a systematic review of treatment outcomes. Murray, SB., Strober, M., Tadayonnejad, R., et al.[2022]

A randomized, double-blind, placebo-controlled trial will assess the efficacy of transcranial direct current stimulation (tDCS) on 80 children and adolescents (ages 10-18) with Anorexia Nervosa, aiming to improve clinical outcomes and reduce symptoms over six weeks of treatment.

The study will also explore changes in brain mechanisms and biomarkers, including PFC connectivity and stress response, which may provide new insights into effective treatments for Anorexia Nervosa in younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of non-invasive brain stimulation in the treatment of children and adolescents with Anorexia Nervosa: study protocol of a randomized, double blind, placebo-controlled trial. Ursumando, L., Ponzo, V., Monteleone, AM., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (TaVNS) effectively normalized gastric dysrhythmias in healthy individuals during a water-load test, indicating its potential as a treatment for gastric symptoms.

The study found that TaVNS at 40 Hz improved heart rate variability and reduced bloating, suggesting it positively influences both parasympathetic and sympathetic nervous system pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. Du, P., Maharjan, A., Calder, S., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a safe and effective neuromodulation therapy for a variety of conditions, including epilepsy, depression, and anxiety, indicating its broad therapeutic potential.

Despite its effectiveness, there is currently no standardization among taVNS devices, and further research is needed to clarify the relationship between stimulation parameters and therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. Wang, L., Wang, Y., Wang, Y., et al.[2022]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly improves depression symptoms, as evidenced by reduced scores on the Hamilton Depression Scale in a review of 12 studies involving 838 participants.

taVNS shows comparable response rates to traditional antidepressants and has fewer side effects, suggesting it could be a safe alternative or complementary treatment for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. Tan, C., Qiao, M., Ma, Y., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

In a study involving at-risk infants receiving transcutaneous auricular vagus nerve stimulation (taVNS) paired with bottle feeding for 2-3 weeks, significant improvements in head movement skills were observed in those who successfully transitioned to full oral feeds, indicating the potential efficacy of taVNS in enhancing motor function.

The study also found that improvements in specific motor skills, such as rolling by arm, were linked to changes in white matter microstructure, suggesting a possible mechanism of action for how taVNS may support motor development in infants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation (taVNS) given for poor feeding in at-risk infants also improves their motor abilities. Aljuhani, T., Haskin, H., Davis, S., et al.[2023]

Transcutaneous auricular Vagus Nerve Stimulation (taVNS) can be optimized by varying electrode designs, which significantly affects the sensitivity and selectivity of nerve activation in different regions of the ear, as shown through a detailed anatomical model and finite element analysis.

The study found that smaller electrodes increase the electric field strength for a given current, allowing for more targeted stimulation of specific ear regions, which is crucial for enhancing the efficacy of taVNS in clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). Kreisberg, E., Esmaeilpour, Z., Adair, D., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive and cost-effective method for modulating the vagus nerve, making it a promising alternative to traditional surgical vagus nerve stimulation.

taVNS allows for easy and safe administration, with considerations for proper electrode placement and individual dosing based on perception thresholds, which enhances its potential for treating various central and peripheral diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. Badran, BW., Yu, AB., Adair, D., et al.[2020]

Transcutaneous auricular Vagus Nerve Stimulation (Ta-VNS) showed significant improvements in depressive symptoms and anxiety levels among 15 female subjects with eating and feeding disorders over a 9-week treatment period, as indicated by reductions in the Hamilton Depression Rating Scale and Beck Anxiety Index scores.

Participants with anorexia nervosa and bulimia nervosa experienced a notable increase in Body Mass Index (BMI), with gains ranging from 5% to 11%, suggesting that Ta-VNS may be a beneficial adjunct therapy for improving both psychological and physical health in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trans-auricular Vagus Nerve Stimulation in the Treatment of Recovered Patients Affected by Eating and Feeding Disorders and Their Comorbidities. Melis, Y., Apicella, E., Macario, M., et al.[2020]

A systematic review of 261 studies revealed significant confusion in the nomenclature for transcutaneous stimulation of the auricular branch of the vagus nerve (ABVN), with 67 full and 27 abbreviated terms identified, highlighting the need for standardization.

The most commonly used terms were 'transcutaneous vagus nerve stimulation' and 'tVNS', but there was no consistent one-to-one relationship between full and abbreviated names, indicating a lack of uniformity in terminology across different research teams.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. Wang, Y., Li, L., Li, S., et al.[2023]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Physical and psychological factors influencing heart rate variability in anorexia nervosa. [2019]

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

Psychological aspects of anorexia nervosa. [2004]

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

Electrical stimulation in the lateral hypothalamus in rats in the activity-based anorexia model. [2008]

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

Neurosurgery and neuromodulation for anorexia nervosa in the 21st century: a systematic review of treatment outcomes. [2022]

5. England pubmed.ncbi.nlm.nih.gov

The efficacy of non-invasive brain stimulation in the treatment of children and adolescents with Anorexia Nervosa: study protocol of a randomized, double blind, placebo-controlled trial. [2023]

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

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulators: a review of past, present, and future devices. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

The efficacy and safety of transcutaneous auricular vagus nerve stimulation in the treatment of depressive disorder: A systematic review and meta-analysis of randomized controlled trials. [2023]

9. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation (taVNS) given for poor feeding in at-risk infants also improves their motor abilities. [2023]

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

High-resolution computational modeling of the current flow in the outer ear during transcutaneous auricular Vagus Nerve Stimulation (taVNS). [2023]

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

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations. [2020]

13. Croatia pubmed.ncbi.nlm.nih.gov

Trans-auricular Vagus Nerve Stimulation in the Treatment of Recovered Patients Affected by Eating and Feeding Disorders and Their Comorbidities. [2020]

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

Toward Diverse or Standardized: A Systematic Review Identifying Transcutaneous Stimulation of Auricular Branch of the Vagus Nerve in Nomenclature. [2023]