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

Background Nucleoside reverse transcriptase inhibitors (NRTIs) disrupt neuronal mitochondrial DNA synthesis, resulting in antiretroviral toxic neuropathy (ATN). Acetyl-l-carnitine (ALCAR) enhances neurotrophic support of sensory neurones, potentially providing symptom relief and nerve regeneration. Objective The objective of the study was to assess the safety and efficacy compared to placebo of intramuscular ALCAR in HIV-positive patients with symptomatic distal symmetrical polyneuropathy. Methods Ninety patients were enrolled and randomized to receive ALCAR [500 mg twice a day (bid); n=43] or placebo (n=47) intramuscularly twice daily for 14 days followed by 42 days of oral ALCAR 1000 mg bid. Assessment of pain was obtained using the Visual Analogue Scale (VAS), Total Symptom Score (TSS), Clinical Global Impression of Change, McGill Pain Questionnaire (MPQ), and the need for rescue analgesics. Results There was no statistically significant difference in changes in VAS over 14 days between groups for the intent-to-treat (ITT) population, but for the efficacy-evaluable (EE) population ALCAR treatment produced a significantly greater reduction in pain compared with placebo (P=0.022). The proportion of patients with an improvement in TSS over 14 days was greater in the ALCAR group compared with the placebo group, but the differences were not statistically significant. During the open-label phase, patients experienced an improvement in pain, as measured by the VAS, TSS and McGill Pain Questionnaire. Conclusion ALCAR, administered twice a day intramuscularly to HIV-1-infected patients with symptomatic ATN, significantly reduced weekly mean pain ratings on the VAS compared with placebo. Treatment with oral ALCAR improved symptoms for the patient group as a whole. Intramuscular and oral ALCAR was generally safe and well tolerated.