Ignite Creation Date:
2025-12-25 @ 2:23 AM
Ignite Modification Date:
2025-12-27 @ 11:46 PM
Study NCT ID:
NCT05490134
Status:
RECRUITING
Last Update Posted:
2025-12-18
First Post:
2022-08-02
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
RM1 Project 1 - tAN Naloxone
Sponsor:
Medical University of South Carolina
Organization:
Study Overview
Official Title:
Evaluating the Specific Role of Endogenous Opioids as the Mechanism Underlying tAN-based Analgesia in Healthy Individuals
Status:
RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This two-visit, randomized, double-blind, sham-controlled trial, uses a novel naloxone blockade model in 136 individuals to determine whether the analgesic effects of a 30-minute transcutaneous auricular neurostimulation (tAN) intervention are mediated through a release of endogenous opioids. Analgesic effects of four various stimulation interventions will be measured (auricular vagus, auricular trigeminal, combination, or sham) while varying the type of intravenous (IV) infusion (either naloxone or saline) a participant is administered to determine whether the analgesic effects are mitigated by pharmacological opioid receptor blockade.
Detailed Description:
The demand for chronic pain treatment has demonstrated an unprecedented increase over the last several decades, in part contributing to an unsustainable surge in opioid prescriptions. Countless patients were escalated to prolonged, high-dose opioid regimens over years of treatment. By 2014, 5.4% of US adults were estimated to use prescription opioids on a long-term basis. As the harms of opioid proliferation became increasingly clear, a dramatic paradigm shift occurred in which these drugs came to be seen as often more dangerous than beneficial for chronic pain. New clinical guidelines highlighted the risks of high-dose regimens as well as limited benefits, particularly insufficient analgesia, associated with long-term use. According to this new perspective, the preferred therapeutic modality for many patients is to significantly reduce, or even completely stop, using opioids.
Stimulation of the auricular branch of the vagus nerve (ABVN) has demonstrated additional benefits for reducing the need for opioids for pain as well as lessening opioid withdrawal symptoms. Clinical trials of ABVN stimulation as an adjunctive treatment for pain have noted decreased intake of tramadol, remifentanil, morphine, as well as naproxen plus tramadol. A pioneering study of electrical stimulation at the cymba conchae in eight persons with opioid use disorder found significantly reduced withdrawal symptoms: first, decreases in anxiety, craving for opioids, chills, nausea; second, reduced bone and joint pain. Results in follow-up clinical trials bolstered the efficacy of ABVN stimulation for opioid withdrawal. More recently, an open-label trial of simultaneous ABVN and trigeminal stimulation found reduced withdrawal symptoms and decreased need for morphine maintenance in newborns with neonatal opioid withdrawal syndrome (see Preliminary Studies, below). This method of simultaneous vagal and trigeminal stimulation via the external ear is known as transcutaneous auricular neurostimulation (tAN), as the targets of electrical stimulation include the ABVN and auriculotemporal nerve (ATN), which is a branch of the mandibular division of the trigeminal nerve. Electrodes applied to select dermatome regions can target ear neural structures and deliver non-invasive VNS and TNS.
Use of tAN devices for pain relief is an attractive alternative to pharmacologic and opioid-based approaches because it is safe and effective and presents no addiction liability. In order to increase clinical adoption and optimize efficacy of these devices, the mechanism of action must be fully characterized.
This study is investigating the anti-pain mechanism behind tAN in a healthy cohort. This study begins to understand whether the anti-pain effects are driven by a release of endogenous opioids - and will accomplish this by administering tAN during aμ-opioid receptor blockade (via naloxone IV). Administering tAN concurrently with IV Naloxone or Saline (control) will allow us to better understand what underlying mechanism drives the analgesic effects of tAN, and whether the blockade of opioid receptors blocks the anti-pain effects of tAN.
Stimulation of the auricular branch of the vagus nerve (ABVN) has demonstrated additional benefits for reducing the need for opioids for pain as well as lessening opioid withdrawal symptoms. Clinical trials of ABVN stimulation as an adjunctive treatment for pain have noted decreased intake of tramadol, remifentanil, morphine, as well as naproxen plus tramadol. A pioneering study of electrical stimulation at the cymba conchae in eight persons with opioid use disorder found significantly reduced withdrawal symptoms: first, decreases in anxiety, craving for opioids, chills, nausea; second, reduced bone and joint pain. Results in follow-up clinical trials bolstered the efficacy of ABVN stimulation for opioid withdrawal. More recently, an open-label trial of simultaneous ABVN and trigeminal stimulation found reduced withdrawal symptoms and decreased need for morphine maintenance in newborns with neonatal opioid withdrawal syndrome (see Preliminary Studies, below). This method of simultaneous vagal and trigeminal stimulation via the external ear is known as transcutaneous auricular neurostimulation (tAN), as the targets of electrical stimulation include the ABVN and auriculotemporal nerve (ATN), which is a branch of the mandibular division of the trigeminal nerve. Electrodes applied to select dermatome regions can target ear neural structures and deliver non-invasive VNS and TNS.
Use of tAN devices for pain relief is an attractive alternative to pharmacologic and opioid-based approaches because it is safe and effective and presents no addiction liability. In order to increase clinical adoption and optimize efficacy of these devices, the mechanism of action must be fully characterized.
This study is investigating the anti-pain mechanism behind tAN in a healthy cohort. This study begins to understand whether the anti-pain effects are driven by a release of endogenous opioids - and will accomplish this by administering tAN during aμ-opioid receptor blockade (via naloxone IV). Administering tAN concurrently with IV Naloxone or Saline (control) will allow us to better understand what underlying mechanism drives the analgesic effects of tAN, and whether the blockade of opioid receptors blocks the anti-pain effects of tAN.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: