The Use of Valeriana officinalis (Valerian) in Improving Sleep in Patients Who Are Undergoing Treatment for Cancer: A Phase III Randomized, Placebo-Controlled, Double-Blind Study (NCCTG Trial, N01C5)

The primary end point of treatment effectiveness was measured using the normalized AUC calculated using baseline, week 4, and week 8 PSQI total scores. The Wilcoxon rank-sum test P value for the total PSQI score was nonsignificant (valerian AUC = 51.4, SD = 16; placebo AUC = 49.7, SD = 15; P = 0.696) (Figure 2). Similarly the FOSQ was not significantly different between groups either overall or on any subscale score.

Supplemental and exploratory analyses using changes from baseline, however, showed a significant difference in the change from baseline in the amount of sleep at night at week 4 (P = 0.008), favoring the valerian group. Change from baseline in the categorical value for sleep latency was also significantly different at week 4, where 10% of valerian patients indicated longer time to fall asleep compared to 28% on placebo and 43% of valerian patients reported less time to fall asleep compared to 32% on placebo (P = 0.03) (Table 3). The ITT analysis indicated that about 9% more patients experienced a success on valerian relative to placebo, but this was not statistically significant. When scores on the PSQI were divided into ≤5 and >5 (this latter group representing sleep problems), there were fewer patients in the valerian group having sleep problems by week 8 (64% vs 80%, P = 0.56).

While the POMS AUC scores indicated no difference between treatment arms, the mean change from baseline at weeks 4 and 8 was significantly different for the Fatigue-Inertia subscale at weeks 4 (P = 0.004) and 8 (P = 0.02), with the valerian arm reporting better scores (Table 4). On the BFI, the valerian arm scored significantly better than the placebo arm in the mean change from baseline at weeks 4 and 8 on the Fatigue Now (P = 0.003 and P = 0.01, respectively) and Usual Fatigue (P = 0.02 and P = 0.046, respectively) items (Table 4).

In terms of toxicity, there were no significant differences between arms for the self-reported side effect items (headache, trouble waking, nausea) at baseline, week 4, or week 8 (Table 5). The valerian arm change from baseline at both weeks 4 and 8 showed significant improvement in drowsiness (P = 0.04 and P = 0.03, respectively) and sleep problems (P = 0.005 and P = 0.03, respectively) compared to placebo (Table 5). The maximum severity over time for each self-reported toxicity resulted in no significant differences between arms. There was a significant difference in the CTCAE reporting of alkaline phosphatase, with the placebo arm having a higher incidence of grade 1 toxicity (P = 0.049).