Non-invasive Therapy to Drive Nerve Regeneration

Peripheral nerve injuries are frequent and disabling, often with irreversible consequences. Injured sensory and motor neurons induce cellular and molecular events we refer to as the intrinsic repair program, linked to their regeneration capacity. Regrettably, regeneration of these nerves is challenging. Issues include whether the intrinsic repair program is robust enough, or is sustained long enough, to ensure repair over long distances. This can result in incomplete repair and/or pain states. The investigators will exploit acute intermittent hypoxia (intermittent periods of reduced oxygen), a novel treatment to condition/prime peripheral nerves and induce an enhanced intrinsic repair program. Acute intermittent hypoxia is non-invasive and has a systemic effect which is a major advantage in cases where there are multiple nerve injured in a widespread distribution, as opposed to electrical stimulation that only impacts the individual nerve stimulated. However, the full potential of acute intermittent hypoxia in nerve repair remains unknown. This will be a Phase I randomized control trial of carpal tunnel syndrome associated with severe median nerve compression/injury. This is designed to test the hypothesis that acute intermittent hypoxia before and/or after nerve decompression will result in more effective nerve regeneration and restoration of function.

Methods:

Using a double blinded randomized controlled trial design, we will recruit 80 adult patients (50% male; 50% female) >18 yrs old with severe carpal tunnel syndrome.

Statistical analysis:

Distribution of the outcome data will be analyzed using the Shapiro-Wilk test. For parameters that are normally distributed, differences between the groups will be compared using 2-way analysis of variance (ANOVA) with time and treatment allocation being the independent factors. When a statistically significant difference (p<0.05) is found, post hoc testing will be done using the Tukey test. For data that is not normally distribution, the Kruskal-Wallis test will be used instead, followed by post hoc analysis with Dunn's test when a significant difference is found. Sample size estimation - Assuming that AIH has a modest treatment effect size of 0.6 compared to the Normoxia control group, with type I error set at 0.05 and type II error at 0.80, appropriately 20 subjects are needed in each group to provide sufficient power for the study.

Inclusion criteria

i) sensory impairments including numbness and pain; ii) nocturnal awakening by these symptoms; iii) weakness and wasting of the thenar musculature and, iv) loss of hand dexterity. v) Motor unit loss greater than 2 SD below the mean for the age group

Exclusion criteria

i) Chronic lung or cardiac disease ii) Other nerve disorders, previous carpal tunnel release or systemic illness including diabetes