Delivering Transcutaneous Auricular Neurostimulation to Reduce Heavy Menstrual Bleeding in Patients With and Without Von Willebrand Disease (VWD/HMB)

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.

Study Overview

• Status: Completed
• Conditions: Heavy Menstrual Bleeding; Von Willebrand Disease, Type 1
• Intervention / Treatment: Device: Volta System

Detailed Description

This study is designed as an open label, two-arm, decentralized clinical study in which patients with heavy menstrual bleeding (HMB) will receive tAN, which targets the auricular branch of the vagus nerve (ABVN) and the auriculotemporal nerve (ATN). Participants will be enrolled into one of two cohorts of the study over the course of two consecutive menstrual cycles.

1. Patients with VWD Type 1 who are on hormone therapy (n=15)
2. Patients with no known cause of HMB who are not currently on hormone therapy (n=15)

During the First Menstruation (baseline), no tAN treatment will be delivered. Participants will estimate blood loss daily throughout the duration of the menstruation phase of their first menstrual cycle. Dysmenorrhea, a general quality of life assessment, and total duration of menstruation will be collected on the final day of first menstruation.

During the Second Menstruation, participants will self-administer 2, 1-hour sessions (daily total of 2 hours) of active tAN daily beginning Day 1 of menstruation through the final day of second menstruation. Participants will estimate blood loss daily throughout the duration of the menstruation phase of their second menstruation. Dysmenorrhea, a general quality of life assessment, and total duration of menstruation will be collected on the final day of second menstruation.

• Study Type: Interventional
• Enrollment (Actual): 29
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75252
      • Five Liters

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Regularly menstruating female participants between 18-45 years of age
2. Typical length of menstruation ranging from 7 to 14 days
3. History of menorrhagia as assessed by the Menstrual Bleeding Questionnaire
4. For patients who have been diagnoses with von Willebrand Disease Type 1: On hormone therapy (with the exception of Nexplanon- at least three months) and willing to continue use for the duration of the study
5. For participants with idiopathic heavy menstrual bleeding: No use of hormon therapy for at least the past three months
6. No changes to all current medications and supplements in the past three months, willingness to continue use for duration of study, and not start any new medications or homeopathic remedies
7. Reliable access to an Internet-enabled device to complete required questionnaires
8. Willingness to consistently use the same brand of tampons and/or pads throughout duration of the study

Exclusion Criteria:

1. Pregnancy within three months of enrollment
2. Lactating at the time of enrollment
3. Antifibrinolytic use within 30 days of enrollment
4. Acquired bleeding disorder
5. Use of anticoagulants (i.e., Aspirin, Warfarin, Coumadin, etc.) including platelet inhibitors for 30 days prior to enrollment
6. Use of the Copper intrauterine device within the past 3 months
7. Known structural cause of heavy menstrual bleeding
8. Use of menstrual cups as a method of menstrual blood collection
9. Participant has a history of chronic tobacco use or has ingested nicotine via smoking, vaping, smokeless tobacco, or nicotine patches in the past three months
10. Participant has received a blood transfusion within 30 days prior to study
11. Participant has a history of epileptic seizures
12. Participant has a history of neurologic diseases or traumatic brain injury
13. Participant has presence of devices (e.g., pacemakers, cochlear prostheses, neurostimulators)
14. Participant has abnormal ear anatomy or ear infection present
15. Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants are risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Von Willebrand Disease (VWD) Patients; Participants with VWD Type 1 who are on hormone therapy. First Menstruation (baseline/no active tAN) followed by Second Menstruation (active tAN)	Device: Volta System; The Volta System will be using the components of the Sparrow Ascent device: (FDA-cleared K230796) a wearable, battery-operated, neurostimulation system designed to transcutaneously stimulate nerves on and/or around the auricle. During Second Menstruation, participants will self-administer 2, 1-hour sessions of active tAN daily with the Volta System Device beginning Day 1 of second menstruation through the final day of second menstruation.
Experimental: Heavy Menstrual Bleeding (HMB) Patients; 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)	Device: Volta System; The Volta System will be using the components of the Sparrow Ascent device: (FDA-cleared K230796) a wearable, battery-operated, neurostimulation system designed to transcutaneously stimulate nerves on and/or around the auricle. During Second Menstruation, participants will self-administer 2, 1-hour sessions of active tAN daily with the Volta System Device beginning Day 1 of second menstruation through the final day of second menstruation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood loss during menses in both groups	Comparison of mean Pictorial Bleeding Assessment Chart (PBAC) scores during first menstruation (no stimulation) versus second menstruation (active stimulation). The PBAC is a widely accepted tool for patients with HMB to account for menstrual blood loss. Menstrual blood loss is estimated through a selection of images of tampons, pads, clots, and flooding events. Patients mark a tally next to the images that best match each of the menstruation products they used that day. This trial will utilize a modified version of the Wyatt et al. 2001 PBAC, where a tally system will be added to each of the images.	Daily throughout both menstruations (up to 2 complete menstrual cycles- estimated 60 days)
Quality of Life in both groups	Comparison of mean quality of life score measured by the Short Form 36 (SF-36) during first menstruation (no stimulation) versus second menstruation (active stimulation). The SF-36 is a 36-item patient-reported questionnaire that assesses general quality of life. This questionnaire includes eight variables: physical functioning, social functioning, role limitations due to physical problems, role limitations due to emotional problems, mental health, energy and vitality, pain, and general perception of health. The SF-36 is scored using a standardized scoring algorithm or by the SF-36 scoring software. The SF-36 scores range from 0 to 100, with higher scores representing better health status.	Final day of each menstruation (up to 2 complete menstrual cycles- estimated 60 days)
Duration and severity of dysmenorrhea in both groups	Comparison of mean Cox Menstrual Symptom Scale (CMSS) scores during first menstruation (no stimulation) versus second menstruation (active stimulation). The CMSS measures menstrual distress and dysmenorrhea. The CMSS Severity subscale is an 18-item self-reported scale that measures severity of menstrual symptoms, including pain, nausea, emotions, etc. during menstruation. The CMSS will be used in this trial to measure a participant's dysmenorrhea every day of each menstruation. Each CMSS item is scored from 0-4, with a higher score indicating higher dysmenorrhea severity.	Final day of each menstruation (up to 2 complete menstrual cycles- estimated 60 days)
Duration of menstruation in both groups	Compare duration of menstruation between first menstruation (no stimulation) versus second menstruation (active stimulation).	Final day of each menstruation (up to 2 complete menstrual cycles- estimated 60 days)

Collaborators and Investigators

• Sponsor: Five Liters, Inc.
• Collaborators: Spark Biomedical, Inc.
• Investigators: Principal Investigator: Navid Khodaparast, PhD, Chief Science Officer; Study Director: Melanie McWade, PhD, Senior Director of Clinical Operations

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2023
• Primary Completion (Actual): April 18, 2025
• Study Completion (Actual): April 18, 2025

Study Registration Dates

• First Submitted: September 15, 2023
• First Submitted That Met QC Criteria: September 26, 2023
• First Posted (Actual): October 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2025
• Last Update Submitted That Met QC Criteria: April 23, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Hemostasis; Menstrual cycle; Hormone therapy; Menorrhagia; Menstruation; Blood loss; Neurostimulation; Transcutaneous auricular vagus nerve stimulation; PBAC; CMSS
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Pathologic Processes; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Genetic Diseases, Inborn; Uterine Diseases; Genital Diseases, Female; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhagic Disorders; Blood Platelet Disorders; Blood Coagulation Disorders, Inherited; Coagulation Protein Disorders; Uterine Hemorrhage; Menstruation Disturbances; Von Willebrand Diseases; Hemorrhage; Menorrhagia; Von Willebrand Disease, Type 1
• Other Study ID Numbers: 5L-BLD-05

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No