GAIT II: No Benefit from Glucosamine/Chondroitin

SALT LAKE CITY—Results from the second phase of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) were released Sept. 30, surprisingly showing no benefit from the nutritional ingredients or a COX-2 inhibitor on joint space width (JSW) loss as compared with a placebo (Arthri Rheumatis. 2008;58(10):3183-91) (DOI:10.1002/art.23973).
The 24-month, double blind, placebo-controlled study, conducted at nine sites in the United States, enrolled 572 patients with knee osteoarthritis (OA). Patients who had been randomized to one of the five groups in the GAIT continued to receive 500 mg of glucosamine three times daily, 400 mg of chondroitin sulfate (CS) three times daily, the combination of glucosamine and CS, 200 mg/d of celecoxib, or a placebo. Mean JSW loss at two years in knees with OA in the placebo group, adjusted for design and clinical factors, was 0.166 mm. No statistically significant difference in mean JSW loss was observed in any treatment group compared with the placebo group. Treatment effects on K/L grade 2 knees, but not on K/L grade 3 knees, showed a trend toward improvement relative to the placebo group. The power of the study was diminished by the limited sample size, variance of JSW measurement and a smaller than expected loss in JSW. Knees with K/L grade 2 radiographic OA appeared to have the greatest potential for modification by these treatments.
Andrew Shao, Ph.D., vice president, scientific and regulatory affairs, CRN, commented: “The results of the GAIT II trial are perplexing and extremely inconsistent with an existing large body of evidence that shows a benefit from glucosamine and chondroitin supplementation. The results are also inconsistent with the first arm of GAIT, as well as with a series of previously published clinical trials which examined the same outcome—the narrowing of the space between joints—and demonstrated clear benefit. This trial was a follow-up to the original GAIT trial, using only a small subset of the original cohort of patients. In addition, anecdotal reports from consumers overwhelmingly indicate that glucosamine and chondroitin, or their combination, are effective.
“Although the study found overall there was no statistically significant difference in the change in JSW among any of the treatment groups, a series of major limitations with this study render its results questionable. For example, the original hypothesis that glucosamine and chondroitin or a combination of the two may slow or prevent normal JSW narrowing due to OA can’t be answered by this trial. The researchers expected to see a typical JSW narrowing of approximately -0.4 millimeters (mm)—yet the actual JSW change in the placebo group was only -0.166 mm, substantially less than what was expected. Because the placebo group did not worsen as expected, there is no basis for comparison. In addition, the study, intending to enroll nearly 800 knee OA patients, ended up being grossly underpowered, with only 357 patients completing the study, due to loss to follow-up and exclusions, making it highly difficult to draw any meaningful conclusions from the results.”