Propionyl-L-carnitine in intermittent claudication: double-blind, placebo-controlled, dose titration, multicenter study

Department of Medicine, University Federico II, Naples, Italy.

OBJECTIVES: The aim of this double-blind, placebo-controlled, dose titration, multicenter trial was to assess the efficacy and safety of propionyl-carnitine in intermittent claudication. BACKGROUND: Human and animal studies indicate that propionyl-L-carnitine increases carnitine content and improves energy metabolism in the ischemic skeletal muscle. METHODS: After a 2-week preliminary period to assess maximal walking distance, 245 patients were randomly assigned to receive propionyl-L-carnitine (n = 118) or placebo (n = 127). The initial oral dose of 500 mg twice daily was increased at 2-month intervals to 2 g/day and then to 3 g/day in patients showing improvement in treadmill performance < 30% over baseline. Efficacy analysis was conducted for the 214 patients who completed the 24 weeks of treatment by comparing the effect of placebo and propionyl-L-carnitine on day 180. RESULTS: Analysis of variance showed a significant improvement of 73 +/- 9% (mean +/- SE) in maximal walking distance with propionyl-L-carnitine (n = 99) compared with 46 +/- 6% for placebo (n = 115, p = 0.03). For distance walked at onset of claudication, propionyl-L-carnitine showed about double the improvement of placebo; however, the difference was not statistically significant. There were no changes in electrocardiographic and routine biochemical and hematologic tests that would indicate an adverse effect of propionyl-L-carnitine. Adverse events requiring drug discontinuation (11 in the propionyl-L-carnitine group, 3 in the placebo group) were unrelated to study medication. The dose titration design of the study also provided information on the dose-response relation. Slightly less than 67% of patients were expected to improve their maximal walking distance by at least 30%, assuming 2 g/day of propionyl-L-carnitine (95% confidence interval 0.51 to 0.70). The response rate during the entire titration course was significantly in favor of propionyl-L-carnitine compared with placebo. CONCLUSIONS: Although the precise mode of therapeutic action requires clarification, propionyl-L-carnitine, at a dose of 1 to 2 g/day, appears to be effective and well tolerated, with minimal adverse effects.

This article has been cited by other articles:

				G. M. Andreozzi, A. Leone, R. Laudani, R. Martin, G. Deinit, and V. Cataldi Levo-Propionyl-Carnitine Improves the Effectiveness of Supervised Physical Training on the Absolute Claudication Distance in Patients With Intermittent Claudication Angiology, March 1, 2008; 59(1): 84 - 89. [Abstract] [PDF]

				A. Silvestro, V. Schiano, R. Bucur, G. Brevetti, F. Scopacasa, and M. Chiariello Effect of Propionylcarnitine on Changes in Endothelial Function and Plasma Levels of Adhesion Molecules Induced by Acute Exercise in Patients with Intermittent Claudication Angiology, March 1, 2006; 57(2): 145 - 154. [Abstract] [PDF]

				M. R Nehler, M. M McDermott, D. Treat-Jacobson, I. Chetter, and J. G Regensteiner Functional outcomes and quality of life in peripheral arterial disease: current status Vascular Medicine, May 1, 2003; 8(2): 115 - 126. [Abstract] [PDF]

				S. M Dean Pharmacologic treatment for intermittent claudication Vascular Medicine, November 1, 2002; 7(4): 301 - 309. [Abstract] [PDF]

				M. Condorelli and G. Brevetti Intermittent claudication: an historical perspective Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B2 - B7. [Abstract] [PDF]

				P. Perrone-Filardi and M. Chiariello Coronary artery disease and intermittent claudication: how to manage the patient Eur. Heart J. Suppl., March 1, 2002; 4(suppl_B): B58 - B62. [Abstract] [PDF]

				W. R. Hiatt Medical Treatment of Peripheral Arterial Disease and Claudication N. Engl. J. Med., May 24, 2001; 344(21): 1608 - 1621. [Full Text] [PDF]

				A. Mancinelli, A. Longo, R. L. Nation, and A. M. Evans Disposition of L-Carnitine and Its Short-Chain Esters, Acetyl-L-carnitine and Propionyl-L-carnitine, in the Rat Isolated Perfused Liver Drug Metab. Dispos., April 13, 2001; 28(12): 1401 - 1404. [Full Text]

				A. J Maxwell, B. E Anderson, and J. P Cooke Nutritional therapy for peripheral arterial disease: a double-blind, placebo-controlled, randomized trial of HeartBar(R) Vascular Medicine, February 1, 2000; 5(1): 11 - 19. [Abstract] [PDF]

				E. P Brass and W. R Hiatt Acquired skeletal muscle metabolic myopathy in atherosclerotic peripheral arterial disease Vascular Medicine, February 1, 2000; 5(1): 55 - 59. [Abstract] [PDF]

				G. Brevetti, C. Diehm, D. Lambert, and on behalf of the Study Investigators European multicenter study on propionyl-L-carnitine in intermittent claudication J. Am. Coll. Cardiol., November 1, 1999; 34(5): 1618 - 1624. [Abstract] [Full Text] [PDF]

				The Investigators of the Study on Propionyl-L-Carn Study on propionyl-L-carnitine in chronic heart failure Eur. Heart J., January 1, 1999; 20(1): 70 - 76. [Abstract] [PDF]

				E. P. Brass and W. R. Hiatt The Role of Carnitine and Carnitine Supplementation During Exercise in Man and in Individuals with Special Needs J. Am. Coll. Nutr., June 1, 1998; 17(3): 207 - 215. [Abstract] [Full Text] [PDF]