Upper respiratory tract infections (URIs) are more common in children than in adults, and parents often treat their children’s symptoms with herbs and other natural health products (NHPs, the regulatory term used in Canada for vitamins, minerals, herbs, homeopathic remedies, etc.). One of the most popular products used for enhancing immunity and preventing and treating URIs in Canada is a special, patented extract of American ginseng root (Panax quinquefolius, Araliaceae) called COLD-fX® (CV Technologies, Inc., Edmonton, Alberta, Canada) consisting of only the saccharide fraction of the root (i.e., furanyl-, oligo- and polysaccharides). Unlike conventional ginseng extracts, this preparation does not contain ginsenosides, the characteristic active triterpene glycosides in various species of the genus Panax that are the subject of most chemical and pharmacological research on this highly-researched genus.
In Canada, COLD-fX is approved by the Natural Health Products Directorate of Health Canada for the prevention and treatment of URIs related to cold and flu, based on a previous review of published clinical trials and laboratory research. Although the safety and efficacy of COLD-fX has been studied for the treatment and prevention of URIs in adults, the authors of this phase II randomized, double-blind, dose-finding, 3-arm clinical trial claim that it is the first to examine safety, dose, and efficacy in children.
There were 2 dosing arms and a placebo arm. The objectives were to document the safety and efficacy of weight-based dosing schedules and to determine the treatment effect of COLD-fX on the severity and duration of pediatric URIs. Children aged 3-12 years old were recruited between November 2005 and February 2006 from 2 teaching hospitals at the University of Alberta (Edmonton, Alberta, Canada). A computerized random number generator was used for randomization.
Parents of the subjects contacted the study nurse upon the onset of symptoms. If the study nurse determined that the symptoms were those of a URI, then the pharmacy was contacted and the study medications (COLD-fX or placebo) were dispensed and sent by courier. The weight-based COLD-fX standard dose (n=13) was 26 mg/kg on day 1, 17 mg/kg on day 2, and 9 mg/kg on day 3. Children who received the standard adult dose (600 mg on day 1, 400 mg on day 2, and 200 mg on day 3) weighed over 45 kg. The weight-based COLD-fX low-dose group (n=14) received 13 mg/kg on day 1, 8.5 mg/kg on day 2, and 4.5 mg/kg on day 3. Children in the low dose group also weighed less than 45 kg. The placebo group (n=15) received a liquid solution similar in appearance to the COLD-fX formulation. The placebo or COLD-fX formulations were dispensed into 3 equal portions to be taken 3 times daily for 3 days. The children received other medications and tests as determined by their physicians. The severity and duration of the URIs were measured using the Canadian Acute Respiratory Infection Flu Scale (CARIFS) score, a validated 18-item scale that covers 3 domains: symptoms, function, and parental impact. The severity and duration of the treatment effect was measured as the average length of time in days from treatment onset to resolution of symptoms, defined as a 25% decrease from the baseline CARIFS score.
No serious adverse events were reported. A total of 31 subjects reported 51 adverse events. Out of these, 8 were classified as moderate: 2 in the low-dose group (fever and secondary bacterial throat infection), 6 in the placebo group, and none in the standard dose group. In addition, 11 adverse events were classified as possibly related to the intervention. Those receiving the standard dose had fewer of these adverse events than either those receiving low-dose or placebo, but there was no statistically significant between-group difference.
The severity and duration of treatment effect was 1.5 days for the standard dose group, 1.9 days for the low dose group, and 1.9 days for the placebo group. This is all-the-more impressive given that those in the standard dose group were the sickest group at the outset. Nevertheless, the study group was too small for this trend to reach statistical significance. From this information, however, the authors were able to calculate that repeating the study with 48 children in each treatment arm could confirm whether COLD-fX shortens the duration of colds in children. The use of antipyretics (fever-reducing medications) was highest in the low-dose group (P=0.48). Otherwise, there was no significant difference in the use of cold and flu remedies, antibiotics, or asthma medications among the groups.
The authors conclude that the standard weight-based dose of COLD-fX used in this study is safe and well-tolerated in children and appropriate for larger, phase III clinical trials. The difference in the use of NHPs and asthma medication was not significant among the treatment arms, but the authors recommend that future investigators caution subjects not to use other NHPs during the study and to include a specific measure of asthma status. The authors also recommend rigorous stepwise clinical trials from phase I to phase III on NHPs, which could help to avoid expensive negative phase III trials. Future research on the efficacy of COLDfX in the treatment of pediatric URIs is warranted. In addition, the authors recommend studies evaluating daily use of COLD-fX in children for preventing URIs.
In February 2007 the American Botanical Council published an extensive clinical monograph on COLD-fX (also known by the name of its extract, CVT-E002), available on the ABC Web site at http://cms.herbalgram.org/herbclip/306/review44663.html.
—Marissa Oppel, MS