EndometriosisRELIEFNCT06974773
Remote Electrical Stimulation as a Long-term Intervention for Endometriosis Flare Ups
A study testing NettleEndo in people with Endometriosis, run by Samphire Group, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 22 to 45 years, women only
- Conditions the study is for
- Endometriosis
- What is being tested?
- NettleEndo
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Dec 2025to 1 Aug 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 to 45 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 19Show fewer
- 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)
- Pain present on ≥50% of days
- 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).
- Capacity to follow instructions and operate the study device.
Who cannot join
- 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
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- 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.
- Recent surgical intervention for endometriosis within 6 months of enrollment or planned surgical intervention for endometriosis during the study period.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Zeenia Framroze, BA MPhil contact
United States1 site, 1 recruiting
- Recruiting
Alethios, Inc.
San Francisco, California, 94109
Zeenia Framroze, BA MPhil, +1 650-206-8006, support@alethios.com
Nirav Shah, MD, MPH, +1 650-206-8006, zeenia@alethios.com
About this study
Official title: At-Home Transcranial Direct Current Stimulation (tDCS) Using the NettleEndo Device for Reducing Symptoms of Endometriosis - A Pivotal Double-Blind, Randomized, Placebo-Controlled Clinical Trial
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:
Read more
- Does at-home transcranial direct current stimulation (tDCS) reduce daily pain intensity in women with endometriosis?
- 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:
- Use the NettleEndo device at home for 20 minutes per session, five times per week for 12 weeks
- Be randomly assigned to receive either real or sham stimulation through the device
- Complete daily and weekly symptom ratings through a mobile app
- Be followed for 90 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.
Read the detailed description
This is a decentralized, randomized, 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 90-day follow-up phase. Outcomes include pain intensity, mood, sleep, and quality of life. Randomization is stratified by pain level and menstrual cycle status. Interim analyses are planned after approximately one-third and two-thirds of participants complete the intervention.
- Conditions
- Endometriosis
- Being tested
- NettleEndo, Sham NettleEndo Device
- Keywords
- Endometriosis, Dysmenorrhea, Chronic Pelvic Pain, tDCS, Neuromodulation, Women's Health
- Medical subject headings
- Endometriosis, Dysmenorrhea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NettleEndoDevice
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.
Sham NettleEndo DeviceDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Device: Sham NettleEndo Device |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Daily, throughout the study (6 months)
Secondary outcomes (3)
Change in endometriosis-specific quality of life (EHP-30)
Change from baseline in total and subscale scores on the Endometriosis Health Profile-30 (EHP-30), a 30-item scale assessing the quality of life specific to endometriosis. Each item is rated on a 5-point Likert scale (1 = "Not at all," 5 = "Extremely"). The scale includes subscales for Pain, Work, Social Relationships, Health, Sexual Activity, and Emotion, each with its own set of items. The total score ranges from 0 to 120, where 0 = No impact on quality of life and 120 = Maximum impact on quality of life. A higher score indicates worse quality of life.
Measured: Monthly starting at baseline until the end of the study (6 months)
Change in general health status (EQ-5D-5L)
Change from baseline in EQ-5D-5L index scores, a 5-item scale assessing general health status. Each item is rated on a 5-point Likert scale (1 = No problems, 5 = Unable to do). The total index score is calculated based on responses across all five domains, with the score ranging from 0 (representing worst possible health) to 1 (representing best possible health). A higher score indicates better health status.
Measured: Monthly starting at baseline until the end of the study (6 months)
Change in severity of illness and improvement over time (CGI)
The Clinical Global Impressions (CGI) scale is a brief, 3-item rating tool used by clinicians to assess the severity of a patient's illness, their improvement over time, and the efficacy of their treatment.
Measured: Monthly starting at baseline until the end of the study (6 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2025
- Study start4 Dec 2025
- Primary completion1 Jul 2026 (estimated)
- Study completion1 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EndometriosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Samphire Group, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Alethios, Inc.
- Responsible party
- Sponsor
- Investigators
- Nirav Shah, MD, MPH, Principal investigator
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06974773
- Sponsor's protocol ID
- RELIEF25
- Acronym
- RELIEF
- Status last verified
- Dec 2025
- First submitted
- 6 May 2025
- Last updated
- 18 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- At-Home Transcranial Direct Current Stimulation (tDCS) Using the NettleEndo Device for Reducing Symptoms of Endometriosis - A Pivotal Double-Blind, Randomized, Placebo-Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT06974773
- Acronym / sponsor ID
- RELIEF / RELIEF25
- Conditions
- Endometriosis
- Keywords
- Endometriosis, Dysmenorrhea, Chronic Pelvic Pain, tDCS, Neuromodulation, Women's Health
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Samphire Group, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Alethios, Inc.
- Study start
- 4 Dec 2025 (actual)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 1 Aug 2026 (estimated)
- First posted
- 16 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- Does at-home transcranial direct current stimulation (tDCS) reduce daily pain intensity in women with endometriosis?
- 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:
- Use the NettleEndo device at home for 20 minutes per session, five times per week for 12 weeks
- Be randomly assigned to receive either real or sham stimulation through the device
- Complete daily and weekly symptom ratings through a mobile app
- Be followed for 90 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 decentralized, randomized, 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 90-day follow-up phase. Outcomes include pain intensity, mood, sleep, and quality of life. Randomization is stratified by pain level and menstrual cycle status. Interim analyses are planned after approximately one-third and two-thirds of participants complete the intervention.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Active tDCS - NettleEndo Device | Experimental | Device: NettleEndoParticipants 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. |
| Sham tDCS - NettleEndo Device | Sham comparator | Device: Sham NettleEndo DeviceParticipants 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. |
Who may qualify
- Ages
- 22 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (19 listed)
- Female, 22-45 years old
- Assigned female at birth
- Fluent in English
- Capacity to consent
- Confirmed diagnosis of endometriosis by a qualified physician, via:
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NettleEndoThe 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. | Device | Active tDCS - NettleEndo Device |
| Sham NettleEndo DeviceThe 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. | Device | Sham tDCS - NettleEndo Device |
Primary outcome
Change in daily endometriosis-associated pain intensity (NRS)
Time frame: Daily, throughout the study (6 months)
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.
3 secondary outcomes
Change in endometriosis-specific quality of life (EHP-30)
Time frame: Monthly starting at baseline until the end of the study (6 months)
Change in general health status (EQ-5D-5L)
Time frame: Monthly starting at baseline until the end of the study (6 months)
Change in severity of illness and improvement over time (CGI)
Time frame: Monthly starting at baseline until the end of the study (6 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Zeenia Framroze, BA MPhil contact
Nirav Shah, MD, MPH principal investigator
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing NettleEndo in people with Endometriosis, run by Samphire Group, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nirav Shah, MD, MPH (+1 650-206-8006, nirav@investigator.alethios.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in daily endometriosis-associated pain intensity (NRS) (time frame: Daily, throughout the study (6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.