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

Samphire Group, Inc.

Status: Enrolling

Conditions: Endometriosis

Treatments: Device: NettleEndo; Device: Sham NettleEndo Device

Study type: Interventional

Funder types: Industry; Other

Identifiers

NCT06974773

RELIEF25

Details and patient eligibility

About

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.

Full 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.

Enrollment: 120 estimated patients

Sex: Female

Ages: 22 to 45 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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120 participants in 2 patient groups

Active tDCS - NettleEndo Device

Experimental group

Description:

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.

Treatment:

Device: NettleEndo

Sham tDCS - NettleEndo Device

Sham Comparator group

Description:

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.

Treatment:

Device: Sham NettleEndo Device