Neurostimulation for Heavy Menstrual Bleeding

(VWD/HMB Trial)

Overseen By Kimiko Harada

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Five Liters, Inc.

Must be taking: Hormone therapy

Must not be taking: Antifibrinolytics, Anticoagulants

Disqualifiers: Pregnancy, Lactating, Bleeding disorder, 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: Unknown

29 Participants Needed

Trial Summary

What is the purpose of this trial?

The objectives of this study are to determine if transcutaneous auricular neurostimulation (tAN) can modulate hemostasis, improve perceived quality of life, and improve pain during the menstrual cycle of von Willebrand Disease (VWD) patients.

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

No, you don't have to stop taking your current medications. You must not change any medications or supplements and should continue using them for the duration of the study. You also cannot start any new medications or homeopathic remedies.

What data supports the idea that Neurostimulation for Heavy Menstrual Bleeding is an effective treatment?

The available research does not provide specific data supporting the effectiveness of Neurostimulation for Heavy Menstrual Bleeding. Instead, it discusses the use of transcutaneous auricular vagus nerve stimulation (taVNS) for other conditions, such as gastric symptoms and pain management. While taVNS is described as a non-invasive and potentially beneficial treatment for various conditions, there is no direct evidence in the provided information that it is effective for Heavy Menstrual Bleeding. ^{1 2 3 4 5}

What safety data exists for transcutaneous auricular vagus nerve stimulation (taVNS)?

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally considered safe with mild and transient adverse effects. A systematic review and meta-analysis evaluated 177 studies with 6322 subjects and found no significant difference in the risk of adverse events between active taVNS and controls. The most common adverse effects reported were ear pain, headache, and tingling. No severe adverse events were causally linked to taVNS, making it a safe and feasible option for clinical intervention. ^{1 3 5 6 7}

Is Transcutaneous Auricular Neurostimulation (tAN) a promising treatment for heavy menstrual bleeding?

Yes, Transcutaneous Auricular Neurostimulation (tAN) is a promising treatment because it is non-invasive, safe, and has been effective for various conditions like pain, anxiety, and depression. It is also inexpensive and portable, making it accessible for future treatments. ^{1 2 3 4 8}

Research Team

Navid Khodaparast, PhD

Principal Investigator

Chief Science Officer

Melanie McWade, PhD

Principal Investigator

Senior Director of Clinical Operations

Eligibility Criteria

This trial is for regularly menstruating women aged 18-45 with Type 1 von Willebrand Disease who experience heavy menstrual bleeding. Participants must have been on oral birth control for at least three months and agree to maintain their current medication regimen without starting new treatments or homeopathic remedies during the study.

Inclusion Criteria

I have been diagnosed with von Willebrand Disease Type 1.

I haven't changed my medications or supplements in the last 3 months and won't start new ones during the study.

I am a woman aged 18-45 and have regular menstrual cycles.

Treatment Details

Interventions

• Transcutaneous Auricular Neurostimulation (tAN)

Trial Overview The study tests if transcutaneous auricular neurostimulation (tAN) using the Volta System can help manage heavy menstrual bleeding, improve quality of life, and reduce pain in patients with von Willebrand Disease during their menstrual cycle.

Participant Groups

Group I: Von Willebrand Disease (VWD) Patients Experimental Treatment 1 Intervention

Participants with VWD Type 1 who are on hormone therapy. First Menstruation (baseline/no active tAN) followed by Second Menstruation (active tAN)

Group II: Heavy Menstrual Bleeding (HMB) Patients Experimental Treatment 1 Intervention

Participants with no known cause of HMB who are not on hormonal therapy. First Menstruation (baseline/no active tAN) followed by Second Menstruation (active tAN)

Transcutaneous Auricular Neurostimulation (tAN) is already approved in United States for the following indications:

Approved in United States as Transcutaneous Auricular Neurostimulation (tAN) for:

• Relief of opioid withdrawal symptoms

Who Is Running the Clinical Trial?

Five Liters, Inc.

Lead Sponsor

Trials

3

Recruited

70+

Spark Biomedical, Inc.

Industry Sponsor

Trials

14

Recruited

560+

Findings from Research

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 (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]

This study will investigate the effects of transcutaneous auricular vagus nerve stimulation (taVNS) on 15 patients with a minimally conscious state, using five different frequencies (1, 10, 25, 50, and 100 Hz) to determine the optimal stimulation parameters.

The goal is to achieve stable improvements in consciousness levels in patients with disorders of consciousness by optimizing the taVNS neuromodulation technique, with results measured through the coma recovery scale-revised (CRS-R) and resting EEG assessments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. Zhai, W., Jiao, H., Zhuang, Y., et al.[2023]

Transcutaneous auricular Vagal Nerve Stimulation (taVNS) did not show any significant effects on pain perception or nociception in healthy participants, as measured by event-related potentials and sensory testing across three experiments involving 22 and 15 subjects.

Both taVNS and standard cervical VNS (cVNS) failed to produce objective changes in behavioral and cerebral responses to pain stimuli, suggesting that the analgesic effects of taVNS may not be as effective as previously thought.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular VNS applied to experimental pain: A paired behavioral and EEG study using thermonociceptive CO2 laser. Dumoulin, M., Liberati, G., Mouraux, A., et al.[2021]

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 well-tolerated method for treating conditions like drug-resistant epilepsy, but a recent randomized double-blind trial found no significant difference in outcomes between high- and low-stimulation groups.

The most common side effect of taVNS is a tingling sensation or pain at the stimulation site, and while it shows promise, further research is needed to fully understand its efficacy and to potentially gain approval for insurance coverage in Japan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. Yamamoto, T.[2022]

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]

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]

References

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

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

2. 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]

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

Optimizing the modulation paradigm of transcutaneous auricular vagus nerve stimulation in patients with disorders of consciousness: A prospective exploratory pilot study protocol. [2023]

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

Transcutaneous auricular VNS applied to experimental pain: A paired behavioral and EEG study using thermonociceptive CO2 laser. [2021]

5. 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]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical Application of Transcutaneous Auricular Vagus Nerve Stimulation]. [2022]

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

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

8. England pubmed.ncbi.nlm.nih.gov

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