SBIR-STTR Award

Most of the 200k Americans who undergo thoracotomy each year receive opiates to reduce postoperative pain because clinicians have few non-addictive, cost-effective choices to control the severe pain patients often experience in the first two weeks after surgery. Managing pain post-thoracotomy is critical to enable patients to take deep breaths and remove (via coughing) lung secretions that otherwise significantly increase risk of pneumonia and collapsed lung, hospital re-admission and morbidity. The most severe pain associated with thoracotomy is transmitted along the intercostal nerves. But no long-term analgesic or nerve block device exists that can provide safe and effective long-term reduction of pain. While drug cocktails often temporarily reduce pain in many patients, and electrical stimulators provide partial relief (50-75% of patients at best), a universally applicable non-addictive pain treatment modality is needed. A reversible, patient-controlled, non- addictive, intercostal nerve block device would reduce suffering due to thoracotomy, broken ribs and herpes zoster. In this Phase I project, we will develop a minimally invasive thermal nerve block device that can control nerve conduction by gently warming and cooling a short nerve segment between room temperature and warm water temperature. This novel approach is based on the discovery that warm and cool temperature mechanisms of nerve block are different and additive, enabling moderate-temperature nerve block by cycling neural tissues slightly above and below body temperature. Reversible thermal nerve blocks represent a completely new approach to managing pain. Having completed work in felines and met with FDA, Aim #1 will complete the development of the minimally invasive thermal tips for ease of implantation, develop the control system to operate the device safely, and evaluate the functional performance of the system for blocking intercostal nerve pain (C-fiber) signals induced by skin pinprick in anesthetized felines and sheep. The thermal tip will cycle nerve temperatures between 15- 45oC as controlled by an external unit that contains a heater/cooler, electronics and power source. We will demonstrate that a minimally invasive tip can block intercostal pain and accurately hold the nerve at 15oC and 45oC while maintaining surrounding tissue in a range of 35-39oC. In Aim #2, we will evaluate efficacy and preliminary safety in 6 conscious sheep for up to 21 days of continuous nerve block as suggested by FDA. Post-therapy we will monitor nerve function recovery and neuropathology will be done at 7- and 90-days post treatment. Successful completion of Phase I will support development of a human-use device and CRO-led pre-clinical GLP safety and efficacy study in Phase II, which in turn will prepare us for an IDE meeting with FDA.

Public Health Relevance Statement:
Project Narrative Thermaquil has discovered a completely new way of blocking nerve signal transmission and is first applying this method to alleviate pain in situations where addictive drugs are commonly used. As many as 90% of thoracotomy patients receive opiates after surgery and 10-15% become dependent. This project will develop and validate a minimally invasive device that will provide a low-cost, non-addictive, intercostal nerve block to alleviate the most severe pain during and after thoracotomy.

Project Terms:
Acute; Aftercare; American; Analgesics; Animals; base; Biological Models; Body Temperature; C Fiber; Cicatrix; clinical practice; Conscious; cost; cost effective; Coughing; Data; dermatome; design; Development; Devices; Drug usage; Effectiveness; efficacy study; Electric Stimulation; Electrodes; Electronics; Evaluation; experience; Exposure to; Family Felidae; Feasibility Studies; Female; Herpes zoster disease; hospital readmission; Human; Implant; implantation; improved; in vivo evaluation; innovation; Liquid substance; Lung; male; Mechanics; Medical; meetings; Methods; minimally invasive; Modality; Monitor; Morbidity - disease rate; Motor; Muscle; Nerve; Nerve Block; Nerve Pain; Nerve Tissue; Nervous System Physiology; Neural Conduction; Neurologic; Neurology; neuropathology; neurotransmission; novel strategies; Operative Surgical Procedures; Opioid; opioid use; Pain; Pain management; pain patient; pain reduction; pain signal; Patients; Performance; performance tests; Pharmaceutical Preparations; Phase; Pneumonia; Positioning Attribute; Postoperative Pain; Power Sources; pre-clinical; preclinical study; Preparation; Procedures; Property; Recommendation; Recovery; Recovery of Function; relating to nervous system; rib bone structure; Risk; Safety; safety study; sample fixation; Sheep; Side; Signal Transduction; Silicones; Site; Skin; Small Business Technology Transfer Research; success; Suggestion; Surface; Surgical sutures; System; Temperature; Testing; Thoracotomy; Time; Tissues; transmission process; Universities; Ventral thoracic nerve structure; warm temperature; Water; Work

Migraines and headaches are difficult to treat debilitating neurological conditions that leave physicians andtheir patients with few options for sustained relief from severe chronic pain. All available therapies haveconsiderable side-effects or limitations, leading many patients to resort to drug cocktails including narcotics. Toreduce or eliminate the need to use opiates and systemic pharmaceuticals to treat headaches and migraine,Thermaquil developed the first noninvasive, drug-free, patient-controlled reversible nerve block device for longterm pain management based on novel mechanisms-of-action that we discovered.Thermaquil has met with more than 300 physicians and headache patients who have vetted and guided thedevelopment of Thermaquil's noninvasive nerve block device. The system is designed to easily be used duringnormal daily activities. We've demonstrated clear efficacy of thermal neuromodulation in single-arm studieswith highly complex patients who have tried and failed all other available treatments. Our 45 participants'baseline pain of 6.1 ± 1.7 was significantly reduced to 2.6 ± 2.5 ( p < 0.05, p = 6e-12). Most participants havehad constant headache every day over the past 28 days, which would exclude them from most other headacheand migraine clinical trials.The proposed study begins with a 28-day lead-in phase to establish a baseline for participant headachefrequency, intensity, medications used, other healthcare utilization, and quality of life. After the baseline period,all participants are randomized into active or control arms and given a single treatment. The study continuesfor 12 weeks with active versus control therapy arms before all participants are given active therapy for anadditional 12 weeks. This sham-controlled study will provide evidence of the safety and effectiveness of theThermaquil device relieving migraine and headache attacks. Successful completion of the project will 1) justifythe company to pursue a larger efficacy/pivotal trial to move towards regulatory approval and 2) result inadditional investment opportunities for Thermaquil to expedite our clinical program to rapidly bring this productto market to help stop migraine and other pain for individuals with chronic migraine or other headaches.

Public Health Relevance Statement:
Project Narrative Chronic migraines and other headaches and are debilitating neurological conditions that affect millions of Americans, resulting in hundreds of thousands of ER visits annually where many patients are prescribed opioids. Thermaquil has discovered a new way of stopping migraine and other headache pain by noninvasively blocking cranial pain signal transmission that has led to the discontinuation of narcotics and other addictive pain medications. This project will test the Thermaquil system in a randomized controlled trial to demonstrate safety and effectiveness for stopping headache and migraine attacks and preventing migraines and other headaches.

Project Terms: