P-033 - (Poster #33) REVFLEX™, A Superior Muscle Recovery Technology supported by Non-Clinical and Clinical Use Studies

Topical pain relief products commonly contain skin nerve irritants (menthol, methyl salicylate and camphor), which is an approach to pain relief that has not changed for over 50 years. These active ingredients temporarily distract users from pain but do not support muscle relaxation or recovery. REVFLEX™ is a patented next generation, over-the-counter (OTC) topical pain relief product designed to increase blood flow to the skin and provide muscle relaxation and recovery.  The product contains two natural ingredients, each promoting one of two pathways, cGMP and cAMP, that support circulation to healthy tissues and muscles. The first natural ingredient is an amino acid which increases nitric oxide and cGMP. The second natural ingredient is a purified extract of a root botanical, which stimulates the formation of cAMP. This innovative technology presents a new paradigm in muscle pain and recovery management.

Purpose/Objectives:

A scientific laboratory and clinical approach was undertaken to understand the ability of REFLEX to activate cGMP and cAMP pathways in skin (mechanism of action studies) and demonstrate a reduction in muscle pain and soreness after topical application in healthy adults (clinical studies). The non-clinical studies were designed to characterize the ability of REVFLEX to increase cGMP and cAMP concentrations and demonstrate safety (non-irritation) versus placebo controls using ex vivo human skin. Two clinical use studies were conducted to demonstrate REVLFLEX’s effectiveness.  In a direct comparator clinical study design, REVFLEX was evaluated against the competitor brand, Icy Hot in a user testing survey. In the second study, REVFLEX was tested in a larger group of users to evaluate REVFLEX’s specific ability to reduce muscle pain, relax muscles, and allow the user to recover and return to previous activity.

Methods:

For laboratory studies, ex vivo human skin explants and commercially available ELISA kits were used to measure cAMP and cGMP concentrations pre- and post-treatment with REFLEX versus controls at 30 min and 2 hours. Safety was evaluated utilizing ex-vivo human skin and executed under a modified in-vitro skin irritation and non-viability test protocol OED439 up to 24 hours.

For the clinical studies, instructions for use and survey questions were developed for users to provide personal demographics and evaluate the experience after using the REVFLEX product with or without a competitor product. Statistical analysis by the student t-test and the Wilcoxon test were utilized to justify significance for REVFLEX as a superior product in the direct comparator study.

Results:

Studies were performed to evaluate the cGMP pathway.  cGMP concentrations were measured in ex vivo human skin explants pre- and post-treatment at 30 min and 2 hours.  The positive cGMP control (amino acid) stimulated intracellular cGMP levels to a greater extent when compared to controls. The herbal derivative had little to no ability to stimulate intracellular cGMP levels when compared to controls. When the amino acid and the herbal derivative were combined (REVFLEX product), cGMP levels in ex vivo human skin explants were stimulated approximately 10 fold greater than the amino acid alone.

Studies were performed to evaluate the cAMP pathway.  cAMP concentrations were measured in ex vivo human skin explants pre- and post-treatment at 30 min and 2 hours. The positive cAMP control (herbal derivative) stimulated intracellular cAMP levels to a greater extent when compared to controls. The amino acid had little to no effect on stimulated intracellular cAMP levels when compared to controls. When the amino acid and the herbal derivative were combined (REVFLEX product), cAMP levels in ex vivo human skin explants were stimulated approximately 3 fold greater than the herbal derivative alone.

For both pathway studies, cAMP and cGMP were synergistically potentiated when both the amino acid and the herbal derivative were combined in the REVFLEX product. Cell viability was not impacted up to 24 hours for formulations containing the amino acid and the herbal derivative.

REVFLEX has been surveyed in 89 participants. In clinical comparator study, participants compared REVFLEX directly to Icy Hot.  Comparator study results showing 90% of users preferred REVFLEX were statistically significant at ≤0.001 which is well below 0.05, demonstrating that REVFLEX is a superior product to Icy Hot. In a follow-up study with a larger group of randomized users, 90% scored REVFLEX as good or excellent for pain relief, muscle relaxation, and recovery (allowing the user to return to sports activity the next day). 

Conclusions/Implications for future research and/or clinical care:

REVFLEX non-clinical and clinical study results demonstrate the product’s unique mechanism of action and a user’s preference over currently available topical pain care competitor products. REVFLEX non-clinical data (1) demonstrates REVFLEX’s promotion of cAMP and cGMP biochemical pathways to provide muscle recovery, which has been proven through ex-vivo human tissue studies including a safety profile and (2) clinical data confirms REVFLEX has a statistically significant user preference over similar OTC topical products. The REVFLEX product is proposed to be superior to other skin-irritant only formulations because cAMP and cGMP promote the reduction of calcium (Ca⁺²) in the muscle tissues which activates myosin light-chain phosphatase to remove phosphate from myosin to create muscle relaxation. In addition, the product enhances the production and transport of nitric oxide (NO) resulting in vasodilation. Vasodilation of the affected area supports removal of muscular waste products such as lactic acid, builds oxygen and nutrient supply. Overall, these effects synergistically amplify the process for muscle fiber recovery.

REVFLEX provides a complete solution for the treatment of muscle pain and recovery with the inclusion of natural ingredients that synergistically produce greater muscle relaxation and vasodilation which amplify the process for muscle fiber recovery and regeneration.