Sickle Cell DiseaseNCT07090668
Trans-auricular Nerve Stimulation as an Innovative Approach to the Treatment of Pain in Pediatric Patients Suffering From Sickle Cell Disease
A study testing tAN device in people with Sickle Cell Disease, run by Emory University at 1 site in United States.
Trial summary
The goal of this study is to evaluate the effects of transauricular vagus and trigeminal nerve stimulation on the treatment of pain in children with Sickle Cell Disease. The primary objective is to determine the feasibility of using a tAN device to treat pain in pediatric participants with SCD by assessing the… Read more about this study
- Who is it for?
- Ages 7 to 18 years
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- tAN device
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Aug 2025to Jan 2027
- 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 7 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of sickle-cell anemia (HbSS)
- Normal outer ear anatomy and intact skin for tAN placement
- Hospitalized for a pain crisis and experiencing pain as a result of SCD
- Patients must have had at least one prior hospitalization for a sickle cell pain crisis in the past
Who cannot join
- History of seizures
- History of uncontrolled psychiatric illness
- Repeated episodes of autonomic instability (apnea or bradycardia) that are not self-resolving
- Cardiomyopathy
- Diagnosis of Acute Chest Syndrome
- Unrepaired congenital anomalies affecting the cardiovascular or respiratory system
Show all 14Show fewer
- Hemodynamically unstable patients
- Females who are pregnant or lactating. Subjects who refuse a pregnancy test.
- Women of childbearing potential, not using adequate contraception as per the investigator's judgment, or not willing to comply with contraception for the duration of the study
- Patients with a history of surgery within the last 3 months
- Patients who suffered from a stroke within the last 3 months
- Patient admitted with a fever or who develops a fever throughout their hospitalization
- Patients whose disease-modifying therapy (HU, chronic transfusions, etc.) and/or pain medications (gabapentin, pregabalin, etc.) have not yet reached a steady dose
- Patients who have had 3 or more hospitalizations for acute pain crises in a given year
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Children's Hospital of Atlanta: Eagelston
Atlanta, Georgia, 30329
Anna Woodbury, MD, 470-882-8960, awoodbu@emory.edu
Vipin Bansal, MD, 404-630-9552, vbansa7@emory.edu
About this study
The goal of this study is to evaluate the effects of transauricular vagus and trigeminal nerve stimulation on the treatment of pain in children with Sickle Cell Disease.
- The primary objective is to determine the feasibility of using a tAN device to treat pain in pediatric participants with SCD by assessing the completion rate, stimulation tolerability, and acceptability of the intervention measures.
- The secondary objective is to assess the preliminary efficacy of using a tAN device as a remedy for pain in pediatric SCD subjects by analyzing inflammatory serum biomarker levels, the Functional Status Scale (FSS), the Wong-Baker FACES questionnaire, tracking analgesic consumption, and other assessments.
Read the detailed description
The vagus nerve, the body's longest cranial nerve, extends from the brainstem to deep regions of the gastrointestinal tract and plays a vital role in regulating parasympathetic activity across multiple organ systems, including the cardiovascular, respiratory, immune, and nervous systems. Since the early 2000s, vagal nerve stimulation (VNS) has been explored as a therapeutic tool across various diseases, particularly for pain management. VNS can reduce pain by three primary mechanisms: 1) suppressing systemic inflammation, 2) modulating central pain-processing pathways, and 3) alleviating depressive symptoms, which are known to intensify the experience of pain.
Sickle cell disease (SCD) is a genetic blood disorder caused by a point mutation in the β-globin gene, resulting in the production of abnormal hemoglobin (HbS). This leads to polymerization of hemoglobin under low-oxygen conditions, which causes red blood cells to become rigid and sickle-shaped. These malformed cells damage blood vessels and adhere to endothelial surfaces, resulting in vaso-occlusion and impaired blood flow. The subsequent ischemia-reperfusion injury provokes widespread inflammation and produces both acute pain episodes and chronic pain syndromes, often beginning in childhood and persisting throughout life.
The current standard for managing SCD-related pain often involves chronic opioid use, which can lead to dependence, tolerance, and serious side effects. Given the ongoing opioid crisis, there is an urgent need for non-pharmacologic alternatives that are safe, effective, and scalable.
This study proposes the use of transcutaneous auricular vagal nerve stimulation (taVNS) as well as trigeminal auricular nerve stimulation (TAN) -non-invasive methods that stimulates vagal afferents and branches of the trigeminal nerve through the ear-to treat pain in pediatric patients with SCD. taVNS is notable for its excellent safety profile, with minimal to no adverse effects reported in clinical studies. It is a multimodal pain management tool, acting simultaneously on immune, neurologic, and psychological pathways that contribute to pain in SCD.
The innovative aspect of this study lies in its application of a non-invasive, neuroimmune-modulating therapy in a pediatric population with complex pain needs. By potentially reducing the frequency and severity of pain episodes and thereby decreasing reliance on opioids, tAN could transform the clinical approach to pain management in SCD. Ultimately, this research aims to provide a safe, sustainable, and accessible intervention that addresses both the biological and psychosocial dimensions of pain in children and adolescents with SCD.
- Conditions
- Sickle Cell Disease
- Being tested
- tAN device
- Keywords
- sickle cell disease, pain management in Sickle cell disease, Trans-auricular vagal nerve stimulation, trans-auricular nerve stimulation
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
tAN deviceDevice
Sparrow Link tAN device from Spark Biomedical, a non-invasive, adhesive earpiece placed over branches of the trigeminal nerve and vagus nerve near the tragus and mastoid around the ear. The stimulation level is titrated by the investigator to a perceptible but comfortable intensity. Patients cannot adjust the settings themselves, though adjustments can be made upon request.
The device consists of a disposable earpiece connected by a cable to a battery-powered controller (3 AAA batteries). It emits a biphasic, rectangular waveform with a 100 µs interphase and a maximum output of 95V.
| Study group | Role | What they receive |
|---|---|---|
| Controls (Same participant but past data) | No intervention | Participants will serve as their own controls. Using chart review, we will collect data from each participant's previous admission for a pain crisis during which they did not receive tAN treatment and compare it to their current admission, during which they are being treated with tAN |
| tAN group | Experimental | Subjects admitted to CHOA with SCD pain crisis. Receives: Device: tAN device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility: Completion Rate
Completion rate will be calculated by dividing the number of subjects who successfully used tAN for the duration of the trial, divided by the total number of subjects who participated in the trial.
Subjects who prematurely opt to interrupt their participation in the study will not be included in the cohort of patients who successfully completed the study
Measured: Through study completion (an average of 3-7 days)
Stimulation tolerability
Stimulation tolerability will be evaluated daily during hospitalization by asking participants to describe any sensations experienced in response to percutaneous stimulation. Participants will be encouraged to express the sensation in their own words.
The investigator will then further clarify the nature of the sensation-such as whether it feels like burning, tingling, or stabbing-to better characterize the participant's experience.
Measured: Baseline, everyday throughout the study (an average of 3-7 days)
Acceptability of intervention
Acceptability of intervention measure will be assessed using a standardized 4 item questionnaire.
Measured: Baseline, everyday throughout the study (an average of 3-7 days)
Secondary outcomes (5)
Wong-Baker FACES
The Wong-Baker FACES Pain Rating Scale is a widely used tool to help individuals-especially children-communicate their level of pain. It uses a series of six cartoon faces, ranging from a happy face at 0 ("No Hurt") to a crying face at 10 ("Hurts Worst"), allowing patients to point to the face that best describes their pain.
Measured: Baseline, everyday throughout the study (an average of 3-7 days)
Functional Status Scale(FSS)
The FSS evaluates six functional domains: Mental Status, Sensory Function, Communication, Motor Function, Feeding, Respiratory Status Each domain is scored on a scale from 1 to 5. Total score range: 6 (best possible function) to 30 (worst possible function)
Measured: Baseline, everyday throughout the study (an average of 3-7 days)
Change in Interleukin 6 (IL-6) levels
IL-6 is a pro-inflammatory cytokine involved in immune responses, inflammation, and infection.
Typically < 5 pg/mL in serum or plasma
Measured: Baseline, end of the study (an average of 3-7 days)
Change in MCP-1
MCP-1 is a pro-inflammatory chemokine that recruits monocytes and other immune cells to sites of inflammation. In children, elevated MCP-1 levels are seen in conditions such as infections, inflammatory diseases Normal levels in healthy children are typically <100-200 pg/mL
Measured: Baseline, end of the study (an average of 3-7 days)
Change in Tumor necrosis factor (TNF-α)
TNF-α (Tumor Necrosis Factor Alpha) is a key pro-inflammatory cytokine involved in immune activation and systemic inflammation.
Normal levels are typically <10 pg/mL.
Measured: Baseline, end of the study (an average of 3-7 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2025
- Study start12 Aug 2025
- Primary completionJan 2027 (estimated)
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- 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
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- Controlled, single blind feasibility study. Controls will be historical controls, consisting of patients with similar clinical presentations who did not receive tAN
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Anna Woodbury, Emory University
- Investigators
- Anna Woodbury, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07090668
- Sponsor's protocol ID
- STUDY00008398
- Status last verified
- Oct 2026
- First submitted
- 21 Jul 2025
- Last updated
- 22 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trans-auricular Nerve Stimulation as an Innovative Approach to the Treatment of Pain in Pediatric Patients Suffering From Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT07090668
- Acronym / sponsor ID
- STUDY00008398
- Conditions
- Sickle Cell Disease
- Keywords
- sickle cell disease, pain management in Sickle cell disease, Trans-auricular vagal nerve stimulation, trans-auricular nerve stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Study start
- 12 Aug 2025 (actual)
- Primary completion
- Jan 2027 (estimated)
- Study completion
- Jan 2027 (estimated)
- First posted
- 29 Jul 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 study is to evaluate the effects of transauricular vagus and trigeminal nerve stimulation on the treatment of pain in children with Sickle Cell Disease.
- The primary objective is to determine the feasibility of using a tAN device to treat pain in pediatric participants with SCD by assessing the completion rate, stimulation tolerability, and acceptability of the intervention measures.
- The secondary objective is to assess the preliminary efficacy of using a tAN device as a remedy for pain in pediatric SCD subjects by analyzing inflammatory serum biomarker levels, the Functional Status Scale (FSS), the Wong-Baker FACES questionnaire, tracking analgesic consumption, and other assessments.
Detailed description
The vagus nerve, the body's longest cranial nerve, extends from the brainstem to deep regions of the gastrointestinal tract and plays a vital role in regulating parasympathetic activity across multiple organ systems, including the cardiovascular, respiratory, immune, and nervous systems. Since the early 2000s, vagal nerve stimulation (VNS) has been explored as a therapeutic tool across various diseases, particularly for pain management. VNS can reduce pain by three primary mechanisms: 1) suppressing systemic inflammation, 2) modulating central pain-processing pathways, and 3) alleviating depressive symptoms, which are known to intensify the experience of pain.
Sickle cell disease (SCD) is a genetic blood disorder caused by a point mutation in the β-globin gene, resulting in the production of abnormal hemoglobin (HbS). This leads to polymerization of hemoglobin under low-oxygen conditions, which causes red blood cells to become rigid and sickle-shaped. These malformed cells damage blood vessels and adhere to endothelial surfaces, resulting in vaso-occlusion and impaired blood flow. The subsequent ischemia-reperfusion injury provokes widespread inflammation and produces both acute pain episodes and chronic pain syndromes, often beginning in childhood and persisting throughout life.
The current standard for managing SCD-related pain often involves chronic opioid use, which can lead to dependence, tolerance, and serious side effects. Given the ongoing opioid crisis, there is an urgent need for non-pharmacologic alternatives that are safe, effective, and scalable.
This study proposes the use of transcutaneous auricular vagal nerve stimulation (taVNS) as well as trigeminal auricular nerve stimulation (TAN) -non-invasive methods that stimulates vagal afferents and branches of the trigeminal nerve through the ear-to treat pain in pediatric patients with SCD. taVNS is notable for its excellent safety profile, with minimal to no adverse effects reported in clinical studies. It is a multimodal pain management tool, acting simultaneously on immune, neurologic, and psychological pathways that contribute to pain in SCD.
The innovative aspect of this study lies in its application of a non-invasive, neuroimmune-modulating therapy in a pediatric population with complex pain needs. By potentially reducing the frequency and severity of pain episodes and thereby decreasing reliance on opioids, tAN could transform the clinical approach to pain management in SCD. Ultimately, this research aims to provide a safe, sustainable, and accessible intervention that addresses both the biological and psychosocial dimensions of pain in children and adolescents with SCD.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Controlled, single blind feasibility study. Controls will be historical controls, consisting of patients with similar clinical presentations who did not receive tAN
| Arm | Type | Receives |
|---|---|---|
| Controls (Same participant but past data) | No intervention | –Participants will serve as their own controls. Using chart review, we will collect data from each participant's previous admission for a pain crisis during which they did not receive tAN treatment and compare it to their current admission, during which they are being treated with tAN |
| tAN group | Experimental | Device: tAN deviceSubjects admitted to CHOA with SCD pain crisis. |
Who may qualify
- Ages
- 7 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (4 listed)
- Diagnosis of sickle-cell anemia (HbSS)
- Normal outer ear anatomy and intact skin for tAN placement
- Hospitalized for a pain crisis and experiencing pain as a result of SCD
- Patients must have had at least one prior hospitalization for a sickle cell pain crisis in the past
Key exclusion criteria (14 listed)
- History of seizures
- History of uncontrolled psychiatric illness
- Repeated episodes of autonomic instability (apnea or bradycardia) that are not self-resolving
- Cardiomyopathy
- Diagnosis of Acute Chest Syndrome
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 |
|---|---|---|
| tAN deviceSparrow Link tAN device from Spark Biomedical, a non-invasive, adhesive earpiece placed over branches of the trigeminal nerve and vagus nerve near the tragus and mastoid around the ear. The stimulation level is titrated by the investigator to a perceptible but comfortable intensity. Patients cannot adjust the settings themselves, though adjustments can be made upon request. The device consists of a disposable earpiece connected by a cable to a battery-powered controller (3 AAA batteries). It emits a biphasic, rectangular waveform with a 100 µs interphase and a maximum output of 95V. | Device | tAN group |
Primary outcome
Feasibility: Completion Rate
Time frame: Through study completion (an average of 3-7 days)
Completion rate will be calculated by dividing the number of subjects who successfully used tAN for the duration of the trial, divided by the total number of subjects who participated in the trial. Subjects who prematurely opt to interrupt their participation in the study will not be included in the cohort of patients who successfully completed the study
Stimulation tolerability
Time frame: Baseline, everyday throughout the study (an average of 3-7 days)
Stimulation tolerability will be evaluated daily during hospitalization by asking participants to describe any sensations experienced in response to percutaneous stimulation. Participants will be encouraged to express the sensation in their own words. The investigator will then further clarify the nature of the sensation-such as whether it feels like burning, tingling, or stabbing-to better characterize the participant's experience.
Acceptability of intervention
Time frame: Baseline, everyday throughout the study (an average of 3-7 days)
Acceptability of intervention measure will be assessed using a standardized 4 item questionnaire.
5 secondary outcomes
Wong-Baker FACES
Time frame: Baseline, everyday throughout the study (an average of 3-7 days)
Functional Status Scale(FSS)
Time frame: Baseline, everyday throughout the study (an average of 3-7 days)
Change in Interleukin 6 (IL-6) levels
Time frame: Baseline, end of the study (an average of 3-7 days)
Change in MCP-1
Time frame: Baseline, end of the study (an average of 3-7 days)
Change in Tumor necrosis factor (TNF-α)
Time frame: Baseline, end of the study (an average of 3-7 days)
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 22 Oct 2026.
- 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.
Anna Woodbury, MD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing tAN device in people with Sickle Cell Disease, run by Emory University 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 4 inclusion and 14 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 22 Oct 2026. 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. 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 Anna Woodbury, MD (470-882-8960, awoodbu@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility: Completion Rate (time frame: Through study completion (an average of 3-7 days)). The study lists 3 primary outcomes in all. 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 22 Oct 2026.