L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial.

This was a phase III randomized, double-blind, placebo-controlled trial conducted across 24 ECOG-associated sites. In the active intervention arm, 189 adults with invasive cancer and fatigue were randomized; 187 were assigned to placebo.

Participants in the active arm received oral liquid L-carnitine 1 g twice daily for 4 weeks, for a total dose of 2 g/day. The preparation was a levocarnitine solution; the comparator was placebo.

L-carnitine did not improve fatigue compared with placebo in this cancer population. On the primary Brief Fatigue Inventory outcome, the change from baseline to week 4 was −0.96 with L-carnitine versus −1.11 with placebo (P = .57), and both groups improved from baseline, suggesting a placebo effect. Secondary outcomes were also negative, with no between-group differences for FACIT-F fatigue (P = .64), depression (P = .93), pain severity (P = .61), or pain interference (P = .75). Baseline carnitine deficiency did not predict benefit. Grade 5 serious adverse events were rare and did not differ by arm (Fisher's exact P = .64).

The intervention period was short at 4 weeks, which may have limited the ability to detect delayed effects. The outpatient cancer population was clinically heterogeneous, and both arms improved over time, making it difficult to separate treatment effect from placebo response. The trial also showed no subgroup signal among participants with baseline carnitine deficiency.