Intravenous l-carnitine increases plasma carnitine, reducesfatigue, and may preserve exercise capacity in hemodialysis patients

Brass, Eric P.; Adler, Sharon; Sietsema, Kathy E.; Hiatt, William R.; Orlando, Anthony M.; Amato, Antonino; CHIEF Investigators,

« Previous Next »American Journal of Kidney Diseases
Volume 37, Issue 5 , Pages 1018-1028, May 2001

Intravenous l-carnitine increases plasma carnitine, reducesfatigue, and may preserve exercise capacity in hemodialysis patients†

Eric P. Brass
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
- Address reprint requests to Eric P. Brass, MD, PhD, Department of Medicine, Harbor-UCLA Medical Center, 1000 West Carson St, Torrance, CA 90509.
Sharon Adler
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
Kathy E. Sietsema
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
William R. Hiatt
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
Anthony M. Orlando
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
Antonino Amato
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
CHIEF Investigators
- Department of Medicine, Harbor University of California at Los Angeles Medical Center, Torrance, CA, USA
- University of Colorado Health Sciences Center and Colorado Prevention Center, Denver, CO, USA
- Worldwide Clinical Trials, Inc, Kennesaw, GA, USA
- Sigma Tau PharmaceuticalsInc, Gaithersburg, MD, USA
- For the Carnitine in Hemodialysis for Improving Exercise Function (CHIEF) Investigators.

Received 29 June 2000; accepted 29 November 2000.

Abstract

Exercise capacity in patients with end-stage renal disease (ESRD) remains impaired despite correction ofanemia. Carnitine insufficiency may contribute to impaired exercise and functional capacities in patients with ESRD. Two randomized placebo-controlled trials were conducted to test whether intravenous l-carnitine improves exercise capacity (assessed by maximal rate of oxygen consumption [VO_2max]) and quality of life (measured by the Kidney Disease Questionnaire [KDQ]) in patients with ESRD. In study A, patients were administered l.-carnitine, 20 mg/kg (n = 28), or placebo (n = 28) intravenously at the conclusion of each thrice-weekly dialysis session for 24 weeks. In study B, a dose-ranging study, patients were administered intravenous l-carnitine, 10 mg/kg (n = 32), 20 mg/kg (n = 30), or 40 mg/kg (n = 32), or placebo (n = 33) as in study A. The prospective primary statistical analysis evaluated changes in VO_2max in each study and specified that changes in the KDQ were assessed only in the combined populations. l-Carnitine supplementation increased plasma carnitine concentrations, but did not affect VO_2max in either study. Because change in VO_2max showed significant heterogeneity, a secondary analysis using a mixture of linear models approach on the combined study populations was performed. l-Carnitine therapy (combined all doses) was associated with a statistically significant smaller deterioration in VO_2max (-0.88 ± 0.26 versus −0.05 ± 0.19 mL/kg/min, placebo versus l-carnitine, respectively; P = 0.009). l-Carnitine significantly improved the fatigue domain of the KDQ after 12 (P = 0.01) and 24 weeks (P = 0.03) of treatment compared with placebo using the primary analysis but did not significantly affect the total score (P = 0.10) or other domains of the instrument (P > 0.11). Carnitine was well tolerated, and no drug-related adverse effects were identified. Intravenous l-carnitine treatment increased plasma carnitine concentrations, improved patient-assessed fatigue, and may prevent the decline in peak exercise capacity in hemodialysis patients. VO_2max in the primary analysis and other assessed end points were unaffected by carnitine therapy.