Remote Electrical Stimulation as a Long-term Intervention for Endometriosis Flare Ups

NCT06974773 | Recruiting

• 1 other identifier: RELIEF25
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to learn if a wearable brain stimulation device called NettleEndo can reduce chronic pelvic pain and improve wellbeing in women with endometriosis. The study also aims to assess the safety and usability of the device when used at home over several months. The main questions it aims to answer are:

1. 1.Does at-home transcranial direct current stimulation (tDCS) reduce daily pain intensity in women with endometriosis?
2. 2.Does the device also improve mood and sleep quality?
3. 3.Use the NettleEndo device at home for 20 minutes per session, five times per week for 12 weeks
4. 4.Be randomly assigned to receive either real or sham stimulation through the device
5. 5.Complete daily and weekly symptom ratings through a mobile app
6. 6.Be followed for 90 days after completing the intervention to monitor longer-term effects

Conditions

Endometriosis

Keywords

Endometriosis; Dysmenorrhea; Chronic Pelvic Pain; tDCS; Neuromodulation; Women's Health

Outcome Measures

Primary Outcomes (1)

• Change in daily endometriosis-associated pain intensity (NRS)

  Average change from baseline in daily self-reported pain intensity related to endometriosis, using a 0-10 Numerical Rating Scale (NRS). This will be measured separately for dysmenorrhea (Dysmenorrhea NRS; DYS NRS) and non-menstrual pelvic pain (Non-Menstrual Pelvic Pain; NMPP NRS). Collected via mobile app. A decrease in NRS, NMPP NRS and DYS NRS scores indicate a better outcome, as it reflects reduced pain intensity.

  Daily, throughout the study (6 months)

Secondary Outcomes (3)

• Change in endometriosis-specific quality of life (EHP-30)

  Monthly starting at baseline until the end of the study (6 months)

• Change in general health status (EQ-5D-5L)

  Monthly starting at baseline until the end of the study (6 months)

• Change in severity of illness and improvement over time (CGI)

  Monthly starting at baseline until the end of the study (6 months)

Other Outcomes (11)

• Device adherence (number of sessions completed)

  Week 1 to Week 12

• Exploratory - Change in pain catastrophizing (PCS)

  Monthly starting at baseline until the end of the study (6 months)

• Exploratory - Change in insomnia severity (ISI)

  Monthly starting at baseline until the end of the study (6 months)

Study Arms (2)

Active tDCS - NettleEndo Device

EXPERIMENTAL

Participants assigned to this arm will receive active transcranial direct current stimulation (tDCS) using the NettleEndo wearable device. The device delivers 2 mA of stimulation for 20 minutes per session, five sessions per week, for a total of 12 weeks. Stimulation is delivered over the left primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) using pre-programmed settings. Participants complete all sessions at home and log outcomes via a mobile app. Device use is monitored remotely through digital logs.

Device: NettleEndo

Sham tDCS - NettleEndo Device

SHAM COMPARATOR

Participants assigned to this arm will receive sham transcranial direct current stimulation (tDCS) using the NettleEndo wearable device. The device mimics the sensation of active stimulation by ramping up to 2 mA for 20 seconds before turning off, with no therapeutic current delivered for the remainder of the 20-minute session. Participants use the device five times per week for 12 weeks. Sessions are completed at home, and outcome measures are recorded via a mobile app. Device use is remotely monitored via app-based logging. Participants and investigators are blinded to group allocation.

Device: Sham NettleEndo Device

Interventions

NettleEndo DEVICE

The NettleEndo device is a portable, home-use transcranial direct current stimulation (tDCS) system designed to deliver low-intensity electrical stimulation to targeted brain regions. The device delivers a constant current of 2 mA in the active stimulation group, targeting the left primary motor cortex (M1) and left dorsolateral prefrontal cortex (DLPFC) through pre-set electrode positioning.

Active tDCS - NettleEndo Device

Sham NettleEndo Device DEVICE

The sham version of the NettleEndo device is visually identical to the active device and is used under the same schedule. The device is pre-programmed to deliver a brief 2 mA current for 20 seconds at the beginning of each session to mimic the initial skin sensations of active stimulation, after which no current is delivered for the remainder of the session. This allows participants to remain blinded to their group assignment. The device is used with the same electrode positioning as the active version.

Sham tDCS - NettleEndo Device

Eligibility Criteria

• Age: 22 Years - 45 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Female, 22-45 years old
• Assigned female at birth
• Fluent in English
• Capacity to consent
• Confirmed diagnosis of endometriosis by a qualified physician, via:
• Laparoscopic surgery with biopsy-proven endometriosis, OR
• Clear evidence of ovarian endometrioma or deep infiltrating endometriosis on ultrasound/MRI
• Pain levels:
• For menstruating participants, all of the following need to be met:
• Regular menstrual cycles (21-35 days)
• Mean DYS NRS ≥4 during menstrual bleeding days (over the last 28 days, self-assessed)
• AND Mean NMPP NRS ≥4 during non-menstrual days (over the last 28 days, self-assessed)
• For non-menstruating patients, all required:
• Irregular/absent cycles OR post-hysterectomy OR surgically menopausal
• Mean pelvic pain NRS ≥4 (over the last 28 days, self-assessed)

You may not qualify if:

• Pregnancy/breastfeeding or planning to become pregnant in next 6 months
• History of epileptic neurological conditions in the immediate family
• Severe/untreated neurological disease (e.g., epilepsy or seizure disorders, stroke or transient ischemic attack \[TIA\], subarachnoid hemorrhage, traumatic brain injury \[TBI\] with persistent neurological deficits, brain tumors \[malignant or benign\], multiple sclerosis, Parkinson's disease, Alzheimer's disease or other dementias, Huntington's disease, cerebral aneurysms or arteriovenous malformations \[AVMs\], active central nervous system infections \[e.g., meningitis, encephalitis\], hydrocephalus, other neurodegenerative diseases not otherwise specified, or any other neurological condition that, in the opinion of the principal investigator, may increase risk or interfere with study participation or outcomes)
• Metal implants/electronic devices in brain, head, or neck area
• Participating in any other clinical trial
• History of stroke, brain surgery, tumors, head trauma
• Active skin lesions, open wounds, cuts, or infections on the scalp
• Active scalp conditions (dermatitis, eczema, psoriasis)
• Significant scarring/burns/other skin damage on scalp
• Schizophrenia or bipolar disorder
• History of suicidal behavior or clinically significant self-injurious behavior (e.g., one or more suicide attempts, non-suicidal self-injury \[NSSI\], or other behaviors indicative of intent to harm oneself), as determined by participant self-report.
• Treatment plan must be stabilized (≥6 weeks analgesic/ ≥6 months hormonal contraception, and crucially no new medication changes before randomization)
• Planning to commence any new treatment during intervention period
• Lack of capacity to consent
• Participation in a neurotechnology or drug trial in the last 6 months.

Sponsors & Collaborators

• Samphire Group, Inc.: lead
• Alethios, Inc.: collaborator

Study Sites (1)

Alethios, Inc.

San Francisco, California, 94109, United States

RECRUITING

MeSH Terms

Conditions

Endometriosis; Dysmenorrhea

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Menstruation Disturbances; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pelvic Pain; Pain; Neurologic Manifestations; Signs and Symptoms

Study Officials

• Nirav Shah, MD, MPH

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nirav Shah, MD, MPH

CONTACT

+1 650-206-8006; nirav@investigator.alethios.com

Zeenia Framroze, BA MPhil

CONTACT

support@alethios.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a two-arm, parallel assignment clinical trial in which participants are randomly assigned in a 1:1 ratio to receive either active transcranial direct current stimulation (tDCS) or sham stimulation using the NettleEndo wearable device. Each participant remains in their assigned group throughout the 12-week intervention period. The study is double-blind: neither participants nor outcome assessors know group assignment.

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 16, 2025
• Study Start: December 4, 2025
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)