Clinical trial NCT06974773: Remote Electrical Stimulation as a Long-term Intervention for Endometriosis Flare Ups
Official title: At-Home Transcranial Direct Current Stimulation (tDCS) Using the NettleEndo Device for Reducing Symptoms of Endometriosis - A Phase II Double-Blind, Randomized, Placebo-Controlled Clinical Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Endometriosis
Keywords: Endometriosis
Dysmenorrhea
Chronic Pelvic Pain
tDCS
Neuromodulation
Women&amp;#39;s Health
Lead sponsor: Samphire Group, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Alethios, Inc.
First posted: 2025-05-16
Enrollment: 120
Sex: FEMALE
Minimum age (years): 22
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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. Does at-home transcranial direct current stimulation (tDCS) reduce daily pain intensity in women with endometriosis?
2. Does the device also improve mood and sleep quality?

Researchers will compare two groups-one receiving active brain stimulation and one receiving a sham (placebo) stimulation-to see if the active device provides greater improvements in symptoms.

Participants will:

1. Use the NettleEndo device at home for 20 minutes per session, five times per week for 12 weeks
2. Be randomly assigned to receive either real or sham stimulation through the device
3. Complete daily and weekly symptom ratings through a mobile app
4. Wear an optional fitness tracker to collect data on sleep, movement, and heart rate variability
5. Be followed for 60 days after completing the intervention to monitor longer-term effects

All activities are completed remotely using a smartphone app. Participants can contact the study team with questions at any time. The study is double-blind, meaning neither participants nor the researchers assessing outcomes will know who received active or sham treatment until the end of the trial.

Detailed description: This is a decentralised, randomised, double-blind, sham-controlled clinical trial evaluating the efficacy, safety, and usability of the NettleEndo device for managing endometriosis-associated symptoms. The device delivers transcranial direct current stimulation (tDCS) and is used at home for 20 minutes per session, five sessions per week, over 12 weeks. The stimulation targets the left dorsolateral prefrontal cortex (DLPFC) and primary motor cortex (M1), both of which are involved in the modulation of pain and emotional regulation.

Participants are randomly assigned in a 1:1 ratio to receive either active or sham stimulation. The sham group receives a brief stimulation ramp-up (2 mA for 20 seconds) to mimic sensation but no sustained current. All participants use the same wearable device, complete self-report measures through a mobile app, and are blinded to group assignment.

Data are collected using the Alethios platform, a compliant digital health system that supports electronic informed consent, daily and monthly questionnaires, adverse event tracking, and automated session logging. Optional wearable integration allows for passive data capture, including sleep, activity, and heart rate variability.

The trial includes a 12-week treatment period followed by a 60-day follow-up phase. Outcomes include pain intensity, mood, sleep, and quality of life. Randomisation is stratified by hormonal contraceptive use. Interim analyses are planned after approximately one-third and two-thirds of participants complete the intervention.

Eligibility criteria: Inclusion Criteria:

* Female, 22-45 years old
* Assigned female at birth
* Fluent in English
* Capacity to consent
* Confirmed diagnosis of endometriosis by a qualified physician, via:

  1. Laparoscopic surgery with biopsy-proven endometriosis, OR
  2. Clear evidence of ovarian endometrioma or deep infiltrating endometriosis on ultrasound/MRI
* Mean NMPP NRS (non-menstrual pelvic pain) ≥ 2.5 OR ≥1.25 and ≥5 on at least 4 days (self-report)
* DYS NRS (dysmenorrhea-related pelvic pain) ≥4 on ≥2 days (self-report)
* Access to a smartphone with an internet data plan, phone must be iOS 13.4+, or Android 12+.
* No hormonal contraception or at least 6 months of consistent adherence to any hormonal contraception (e.g., IUD, pill, injection)
* Regular menstrual cycles (24-35 days) for the past six months

Exclusion Criteria:

* 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 (4 week analgesic/ 6 month+ hormonal contraception, and crucially no new medication changes)
* Planning to commence any new treatment during intervention period
* Lack of capacity to consent
* No menstruation

Primary outcomes:
measure: Change in daily endometriosis-associated pain intensity (NRS)
timeFrame: Daily, throughout the study (5 months)
Secondary outcomes:
measure: Change in cyclical mood and physical symptoms (DRSP)
timeFrame: Daily, throughout the study (5 months)
measure: Change in depressive symptoms (PHQ-8)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
measure: Change in state anxiety (STAI-S)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
measure: Change in positive and negative affect (PANAS)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
measure: Change in pain catastrophising (PCS)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
measure: Change in insomnia severity (ISI)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
measure: Change in endometriosis-specific quality of life (EHP-30)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
measure: Change in general health status (EQ-5D-5L)
timeFrame: Baseline and monthly through Week 12 and Day 60 Follow-Up
Other outcomes:
measure: Device adherence (number of sessions completed)
timeFrame: Week 1 to Week 12
measure: Incidence of device-related adverse events
timeFrame: Week 1 to Day 60 follow-up
measure: Daily medication use (analgesic and hormonal)
timeFrame: Daily, throughout the study (5 months)
measure: Change in trait anxiety (STAI-T)
timeFrame: Baseline only
measure: Menstrual cycle characteristics and timing
timeFrame: Daily, throughout the study (5 months)
measure: Exploratory analysis of Heart Rate Variability (HRV)
timeFrame: Daily, throughout the study (5 months)
measure: Exploratory analysis of step count
timeFrame: Daily, throughout the study (5 months)
measure: Exploratory analysis of sleep metrics
timeFrame: Daily, throughout the study (5 months)
Locations:
city: San Francisco
country: United States
facility: Alethios, Inc.
state: California
Study officials:
name: Nirav Shah, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: