Kava, Valerian Effects On Anxiety, Insomnia Similar To Placebo – Online Trial

Supplementation with either kava or valerian is no more effective than placebo at relieving anxiety or insomnia, results from the Internet-based KALM Study indicate.

Principal investigator Bradly Jacobs, MD, University of California-San Francisco, found placebo improved subjects' anxiety and insomnia symptoms 14.4% and 8.3%, respectively, but noted the use of kava and valerian did not enhance this response.

Jacobs presented the KALM findings for the first time at the International Scientific Conference on Complementary, Alternative & Integrative Medical Research in Boston April 12-14. The conference was sponsored by NIH's National Center for Complementary & Alternative Medicine, Harvard Medical School and UCSF's Osher Center for Integrative Medicine.

The study's findings with regard to kava come on the heels of rising concerns about the botanical's safety. FDA recently issued a consumer advisory warning the herb may be associated with severe liver injury (¹ (Also see "Kava Labeling Revisions Adopted By Trade Groups; FDA Issues Advisory" - Pink Sheet, 1 Apr, 2002.), p. 4).

The three-arm KALM study, which Jacobs said is the largest randomized, double-blind trial to date on either kava or valerian, followed 391 adults for four weeks and found no adverse events related to either herbal.

Compared to the subjects receiving placebo, who had a 14.4% decrease in anxiety symptoms as measured by a subset of the State-Trait Anxiety Inventory (STAI), those taking kava experienced only an 11.8% decline in anxiety, while those using valerian had an 11.9% drop in anxiety symptoms, Jacobs reported.

Looking at insomnia, which was measured with the Insomnia Severity Index (ISI), Jacobs found that the placebo group experienced an 8.3% decrease in sleep impairment, while participants given kava had a similar nonsignificant 8.1% decline and those receiving valerian had a 7.9% drop in insomnia severity.

Secondary outcomes included the number of minutes required to fall asleep and the number of times subjects awoke during the night. Neither produced statistically significant differences between kava, valerian and placebo, Jacobs said. Multiple subgroup analyses also did not reveal any benefits from the herbs.

Although the trial failed to demonstrate a positive effect of kava and valerian, Jacobs noted the study did show "it is feasible, relatively fast and inexpensive to conduct randomized trials via the Internet."

He pointed out that within six weeks of initiating recruitment, more than 30,000 visits were made to the ² KALM Web site, 1,550 people registered for the trial, 540 qualified to participate and 391 ultimately were randomized to one of the three treatment groups.

Jacobs added that online studies allow for broad geographic participation - KALM included participants from 46 states - as well as better informed consent, since participants have constant access to study researchers via e-mail.

The KALM study was conducted using software developed by San Francisco-based 1747, Inc., which began recruiting participants for the trial in early 2001 through advertisements on various women's health Web sites (³ (Also see "Online Trials Model Being Tested In Kava, Valerian Study" - Pink Sheet, 23 Apr, 2001.), p. 15).

Individuals qualified to participate if they reported difficulty falling asleep or staying asleep during the previous two weeks, scored greater than .5 standard deviations above the mean on two separate STAI tests and had 24-hour access to e-mail.

Once qualified, subjects received either 300 mg kava daily with valerian placebo, 6.4 mg valerian daily with kava placebo or double placebo, all provided by PureWorld Botanicals. Subjects were sent follow-up assessments via email after two and four weeks and were urged to e-mail concerns or adverse events.

While Jacobs concluded online trials are easy and cost-effective, he acknowledged they have some limitations. For instance, studies requiring home-based measurements for disease management do not lend themselves to online testing, he said. Participation also is limited to those with 24-hour Internet access, which Jacobs estimated includes 50%-70% of the U.S. population.

1747 said it plans to license its online trial software to other firms, as well as academic medical centers, and will continue to test supplements, OTC and Rx pipeline drugs. The firm's most recent project is an 80-patient Phase IIIb study of Eli Lilly's erectile dysfunction drug Cialis ; data collection ended in March. 1747 is partially funded by Lilly's e.Lilly R&D venture capital arm.