These data, along with positive results from a Canadian study (CMAJ 2005;173:1043-8), prompted the Wake Forest group to look at the potential of the ginseng extract to reduce infection risk in CLL patients.
A total of 293 untreated CLL patients were randomized to take COLD-FX, 200 mg twice daily, or matching placebo for 3 months. The patients were instructed to keep a daily record of ARI symptoms in written diaries and to rate their symptoms on a 0-3 scale of severity. Subjects also recorded activity limitations, episodes of fever, and antibiotic use.
The patients had a mean age in the mid-60s; 75% of the active treatment group and 78% of the placebo group had been vaccinated against influenza. The investigators excluded people with HIV, cirrhosis, cardiovascular disease, multiple sclerosis, other malignancies, and liver enzyme abnormalities. They also excluded people on immunomodulatory drugs, hematopoietic stem cell recipients, and those on corticosteroids, antibiotics, or warfarin.
Of all subjects, 53% had an ARI during the study period from January to March. On average, ARI days occurred at a rate of 0.1/patient-day. Put another way, 1 of every 10 days is an ARI day for these patients, Dr. Shaw explained. Since only about half of the subjects actually had ARIs, this means that for them 1 out of every 5 days is an ARI symptom day.
Overall, there were no major differences between the treatment and placebo groups in terms of the primary study end points. In the ginseng-treated group, 50% had at least one ARI episode, compared with 55% in the placebo group, but this difference was not statistically significant.
In terms of symptom duration, the ginseng group had a mean total of 8.9 ARI days vs. 6.9 days, but this difference was also deemed not statistically significant.
There were no differences in use of antibiotics or other secondary end points. While there was a trend toward lower incidence of moderate to severe ARIs in patients taking the ginseng supplement (31% vs. 39%), it did not reach significance.
In terms of adverse events, there were 13 "serious" episodes in the ginseng group versus 27 in the placebo group. Diarrhea, dizziness, hyperglycemia, and joint pain were among the most common reported adverse effects, but these were rare, and only 2 of the 40 episodes were considered "possibly related to the treatment."
Both the ginseng-treated and placebo-treated groups showed a mean increase in total white blood cells, with the increase being slightly higher in the placebo group. However, both groups showed a decrease in absolute neutrophil counts. Peripheral blood CD4 cell counts decreased in the active treatment group but increased in the placebo group. None of these differences were statistically or clinically significant.
The study was funded by the National Cancer Institute and Afexa Life Sciences.
The researchers said they did not know why the ginseng extract failed to produce the expected reductions in ARI among these CLL patients, but suggested that it may be a dosing issue. "We went with the dose used in the previous studies of healthy elderly, noncancer patients. It might not have been enough for CLL patients with impaired immune function." Dr. Shaw added that dose-escalation studies are in the works.