Acetyl-l-carnitine to Enhance Nerve Regeneration in Carpal Tunnel Syndrome

Summary

Study Hypothesis: Acetyl-l-carnitine increases nerve regeneration in patients with severe carpal tunnel syndrome. Carpal tunnel syndrome (CTS) is common, affecting almost 3% of the general population. In severe cases, nerve regeneration and functional recovery are incomplete even with surgery. The goal of this pilot project is to test a potentially promising medication, acetyl-l-carnitine (ALCAR). We will use a randomized, double blinded, placebo controlled study design. Along with surgery, those in the treatment group will also receive ALCAR while the other half in the control group will be given placebo. To gauge the effects of ALCAR, we will compare motor and sensory nerve growth as well as functional outcomes. The data from this study will provide crucial information when designing a full scale clinical trial. If successful, this will represent an important first step in finding a novel treatment to improve functional outcomes in patients with severe CTS.

Timeline

Start

2015-09

Primary completion

2017-06

Completion

2017-09

Publications

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• Background Gordon T, Amirjani N, Edwards DC, Chan KM. Brief post-surgical electrical stimulation accelerates axon regeneration and muscle reinnervation without affecting the functional measures in carpal tunnel syndrome patients. Exp Neurol. 2010 May;223(1):192-202. doi: 10.1016/j.expneurol.2009.09.020. Epub 2009 Oct 1.
• Background Gutmann E, Guttmann L, Medawar PB, & Young JZ (1942). The rate of regeneration of nerve. J Exp Biol 19, 14-44.
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• Background McKay Hart A, Wiberg M, Terenghi G. Pharmacological enhancement of peripheral nerve regeneration in the rat by systemic acetyl-L-carnitine treatment. Neurosci Lett. 2002 Dec 16;334(3):181-5. doi: 10.1016/s0304-3940(02)00982-5.
• Background Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr Opin Neurobiol. 2000 Jun;10(3):381-91. doi: 10.1016/s0959-4388(00)00092-1.
• Background Kotil K, Kirali M, Eras M, Bilge T, Uzun H. Neuroprotective effects of acetyl-L-carnithine in experimental chronic compression neuropathy. A prospective, randomized and placebo-control trials. Turk Neurosurg. 2007 Apr;17(2):67-77.
• Background Mazzoni IE, Said FA, Aloyz R, Miller FD, Kaplan D. Ras regulates sympathetic neuron survival by suppressing the p53-mediated cell death pathway. J Neurosci. 1999 Nov 15;19(22):9716-27. doi: 10.1523/JNEUROSCI.19-22-09716.1999.
• Background Sulaiman OA, Gordon T. Effects of short- and long-term Schwann cell denervation on peripheral nerve regeneration, myelination, and size. Glia. 2000 Dec;32(3):234-46. doi: 10.1002/1098-1136(200012)32:33.0.co;2-3.
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• Background Wilson AD, Hart A, Brannstrom T, Wiberg M, Terenghi G. Primary sensory neuronal rescue with systemic acetyl-L-carnitine following peripheral axotomy. A dose-response analysis. Br J Plast Surg. 2003 Dec;56(8):732-9. doi: 10.1016/j.bjps.2003.08.005.
• Background You S, Petrov T, Chung PH, Gordon T. The expression of the low affinity nerve growth factor receptor in long-term denervated Schwann cells. Glia. 1997 Jun;20(2):87-100. doi: 10.1002/(sici)1098-1136(199706)20:23.0.co;2-1.
• Background Youle M, Osio M; ALCAR Study Group. A double-blind, parallel-group, placebo-controlled, multicentre study of acetyl L-carnitine in the symptomatic treatment of antiretroviral toxic neuropathy in patients with HIV-1 infection. HIV Med. 2007 May;8(4):241-50. doi: 10.1111/j.1468-1293.2007.00467.x.
• Results Atroshi I, Gummesson C, Johnsson R, Ornstein E, Ranstam J, Rosen I. Prevalence of carpal tunnel syndrome in a general population. JAMA. 1999 Jul 14;282(2):153-8. doi: 10.1001/jama.282.2.153.
• Curran MW, Olson J, Morhart M, Sample D, Chan KM. Acetyl-L-carnitine (ALCAR) to enhance nerve regeneration in carpal tunnel syndrome: study protocol for a randomized, placebo-controlled trial. Trials. 2016 Apr 14;17:200. doi: 10.1186/s13063-016-1324-2.

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Indications