SBIR-STTR Award

Osteoarthritis (OA) is the most common type of arthritis, affecting over 30 million adults in the United States in 2015 and represents over 25% of medical office visits according to the Centers for Disease Control and Prevention and the National Institutes of Health. Over 40% of individuals over 65 have symptomatic OA and reduced mobility due to the disease. OA pain is often mitigated with conservative treatment approaches such as water therapy, walking, cycling, and pharmaceuticals. Regular use of NSAIDs can have adverse side effects on cardiovascular, gastrointestinal and renal systems. As such, topical NSAIDs are often used and provide similar pain relief to oral NSAIDs. Long-duration ultrasound has been used to reduce pain and improve joint function in patients with knee OA. When ultrasound is used in conjunction with topical pharmaceuticals, sonophoresis drives the molecules deeper into tissue, providing improved pain relief compared to ultrasound alone or topical application of NSAIDs alone. This proposal will develop and evaluate a sonophoresis patch that couples with a long-duration, low-intensity ultrasound wearable device. This battery powered, wearable sonophoresis patch can be self-applied and administers ultrasound through novel NSAID enriched hydrogel coupling patch for extended treatment durations, driving NSAIDs deeper into tissue and providing superior pain relief to topical NSAIDs or ultrasound alone. Key Features of the Proposed Work: (1) First ZetrOZ Systems, LLC will design and evaluate a sonophoresis coupling patch, enriched with NSAIDs (piroxicam 0.5%). Critical ultrasound coupling specifications will be evaluated under bench testing conditions including thermal properties and acoustic coupling. (2) ZetOZ Systems, LLC will assess human factor engineering considerations. A sample of 20 participants will be instructed how to apply the sonophoresis patch and ultrasound device to the OA affected knee during a 10-minute demonstration. Then, participants will apply the sonophoresis patch for five treatment sessions of four hours, with a maximum of one treatment session per day. All five treatment sessions will be performed within a 7-day period. After each treatment session participants will fill out a questionnaire relating to the ease-of-use, repeatability, mobility limitations, or otherwise adverse effects. Human factors considerations are an integral factor in the design process and any necessary changes will be implemented prior to clinical efficacy studies following this project. (3) An 8-week, 50 patient, double-blind randomized clinical efficacy pilot study will be conducted to evaluate the sonophoresis patch compared to long-duration ultrasound treatment. The primary outcome of the study will be pain score, evaluated daily using the numerical rating scale (NRS). Baseline NRS score will include the first two weeks of the study without intervention. Intervention phase will separate two demographically equivalent groups of 25, assigned to use either the sonophoresis or standard gel coupling patch with daily self-applied ultrasound treatment for six weeks. The proposed combination therapy has the potential to deliver a safe, effective, and conservative treatment approach for OA in the aging population.

Project Terms:
Acoustics; active method; Adhesives; Adult; Adverse effects; Adverse reactions; Affect; Age-Years; aging population; Algorithms; Americas; Arthritis; Automobile Driving; base; Cadaver; Cardiovascular system; celecoxib; Centers for Disease Control and Prevention (U.S.); Clinical; clinical efficacy; Clinical Research; Clinical Trials; Combined Modality Therapy; commercialization; Comorbidity; Coupled; Couples; Coupling; Data; Degenerative Disorder; Degenerative polyarthritis; design; Development; Devices; disability; Disease; Distress; Double-Blind Method; Drug Delivery Systems; Economics; efficacy study; Emotional; Engineering; Evaluation; Excision; Exercise; experience; Family suidae; Foundations; gastrointestinal; Gel; Glycols; Health; Health Care Costs; Home environment; Hour; Human; Hydrogels; improved; indexing; Individual; Inflammation; innovation; Intervention; joint function; Kellgren-Lawrence grade; Kidney; Knee; Knee Osteoarthritis; Lead; Legal patent; Medical; Medical Device; Modality; Multi-Institutional Clinical Trial; Non-Steroidal Anti-Inflammatory Agents; novel; Numeric Rating Scale; Office Visits; Oral; osteoarthritis pain; Outcome Study; Output; overtreatment; Pain; Pain management; pain reduction; pain relief; pain score; pain symptom; Participant; Patients; Penetration; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pilot Projects; Piroxicam; placebo controlled study; placebo group; Placebos; Polypropylenes; primary outcome; Process; Property; Questionnaires; Randomized; Risk; Sampling; Self Care; Self-Administered; Skin; Surveys; symptom treatment; symptomatic improvement; Symptoms; System; Technology; Testing; Time; time use; Tissue Model; tissue phantom; Tissues; Topical application; Transdermal substance administration; treatment duration; treatment group; Ultrasonography; United States; United States National Institutes of Health; Walking; Water; wearable device; wearable technology; Western Ontario and McMaster Universities Arthritis Index; Work;

Osteoarthritis (OA) is the most common type of arthritis, affecting over 30 million adults in the United States in 2015 and represents over 25% of medical office visits according to the Centers for Disease Control and Prevention and the National Institutes of Health. Over 40% of individuals over 65 have symptomatic OA and reduced mobility due to the disease. OA pain is often mitigated with conservative treatment approaches such as water therapy, walking, cycling, and pharmaceuticals. Regular use of NSAIDs can have adverse side effects on cardiovascular, gastrointestinal and renal systems. As such, topical NSAIDs are often used and provide similar pain relief to oral NSAIDs. Long-duration ultrasound has been used to reduce pain and improve joint function in patients with knee OA. When ultrasound is used in conjunction with topical pharmaceuticals, sonophoresis drives the molecules deeper into tissue, providing improved pain relief compared to ultrasound alone or topical application of NSAIDs alone. This proposal will develop and evaluate a sonophoresis patch that couples with a long-duration, low-intensity ultrasound wearable device. This battery powered, wearable sonophoresis patch can be self-applied and administers ultrasound through novel NSAID enriched hydrogel coupling patch for extended treatment durations, driving NSAIDs deeper into tissue and providing superior pain relief to topical NSAIDs or ultrasound alone. Key Features of the Proposed Work: (1) First ZetrOZ Systems, LLC will design and evaluate a sonophoresis coupling patch, enriched with NSAIDs (piroxicam 0.5%). Critical ultrasound coupling specifications will be evaluated under bench testing conditions including thermal properties and acoustic coupling. (2) ZetOZ Systems, LLC will assess human factor engineering considerations. A sample of 20 participants will be instructed how to apply the sonophoresis patch and ultrasound device to the OA affected knee during a 10-minute demonstration. Then, participants will apply the sonophoresis patch for five treatment sessions of four hours, with a maximum of one treatment session per day. All five treatment sessions will be performed within a 7-day period. After each treatment session participants will fill out a questionnaire relating to the ease-of-use, repeatability, mobility limitations, or otherwise adverse effects. Human factors considerations are an integral factor in the design process and any necessary changes will be implemented prior to clinical efficacy studies following this project. (3) An 8-week, 50 patient, double-blind randomized clinical efficacy pilot study will be conducted to evaluate the sonophoresis patch compared to long-duration ultrasound treatment. The primary outcome of the study will be pain score, evaluated daily using the numerical rating scale (NRS). Baseline NRS score will include the first two weeks of the study without intervention. Intervention phase will separate two demographically equivalent groups of 25, assigned to use either the sonophoresis or standard gel coupling patch with daily self-applied ultrasound treatment for six weeks. The proposed combination therapy has the potential to deliver a safe, effective, and conservative treatment approach for OA in the aging population.

Public Health Relevance Statement:


Project narrative:
This project proposes to develop and evaluate the first home-use NSAID-enhanced sonophoresis patch for use by an aging population with osteoarthritis. We will finalize development of the ultrasound-based drug delivery system, and evaluate the sonophoresis patch in human factor study and pilot clinical trial on knee osteoarthritis.

NIH Spending Category:
Aging; Arthritis; Bioengineering; Biomedical Imaging; Chronic Pain; Clinical Research; Clinical Trials and Supportive Activities; Osteoarthritis; Pain Research

Project Terms:
Acoustics; active method; Adhesives; Adult; Adverse effects; Adverse reactions; Affect; Age-Years; aging population; Algorithms; Americas; Arthritis; Automobile Driving; base; Cadaver; Cardiovascular system; celecoxib; Centers for Disease Control and Prevention (U.S.); Clinical; clinical efficacy; Clinical Research; Clinical Trials; Combined Modality Therapy; commercialization; comorbidity; Coupled; Couples; Coupling; Data; Degenerative Disorder; Degenerative polyarthritis; design; Development; Devices; disability; Disease; Distress; Double-Blind Method; Drug Delivery Systems; Economics; efficacy study; Emotional; Engineering; Evaluation; Excision; Exercise; experience; Family suidae; Foundations; gastrointestinal; Gel; Glycols; Health; Health Care Costs; Home environment; Hour; Human; Hydrogels; improved; indexing; Individual; Inflammation; innovation; Intervention; joint function; Kellgren-Lawrence grade; Kidney; Knee; Knee Osteoarthritis; Lead; Legal patent; Medical; Medical Device; Modality; Multi-Institutional Clinical Trial; non-opioid analgesic; Non-Steroidal Anti-Inflammatory Agents; novel; Numeric Rating Scale; off-patent; Office Visits; Oral; osteoarthritis pain; Outcome Study; Output; overtreatment; Pain; Pain management; pain reduction; pain relief; pain score; pain symptom; Participant; Patients; Penetration; Periodicity; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Pilot Projects; Piroxicam; placebo controlled study; placebo group; Placebos; Polypropylenes; primary outcome; Process; Property; Questionnaires; Randomized; Risk; Sampling; Self Administration; Self Care; side effect; Skin; Surveys; symptom treatment; symptomatic improvement; Symptoms; System; Technology; Testing; Time; time use; Tissue Model; tissue phantom; Tissues; Topical application; Transdermal substance administration; treatment duration; treatment group; Ultrasonography; United States; United States National Institutes of Health; Walking; Water; wearable device; wearable technology; Western Ontario and McMaster Universities Arthritis Index; Work