GAIT - Purpose and Design
The goal of the study was to conduct a multicenter, double-blind, placebo-controlled, active comparator, two-part, long-term trial to determine the effectiveness of glucosamine and chondroitin in subjects with documented knee osteoarthritis.
The study design utilized five treatment groups (or arms) and 1,583 subjects (over 300 per arm). The total cost is estimated at $16 million.
There were 5 Intervention Groups:
Group 1: orally administered glucosamine HCl alone (1,500 mg)
Group 2: orally administered chondroitin sulfate alone (1,200 mg)
Group 3: combination of glucosamine and chondroitin (in the dosages above)
Group 4: the anti-inflammatory drug celecoxib (Celebrex®) at the FDA approved dose of 200 mg once daily
Group 5: placebo
In phase I of the study (6 months of intervention), changes in pain and function were evaluated. In part II, which will be completed in 2006, about 720 study subjects underwent weight-bearing knee x-ray at the start of the study. They will get x-rays at the end of the two years. By measuring the difference in the width of the space of the joints, the investigators will be able to determine if cartilage was lost or gained during the 2-year intervention. [More on this later].
The investigators had a hard time recruiting study subjects. It is difficult to find arthritis patients who are not taking glucosamine and chondroitin or who are willing to be randomly put into a placebo group (or a group that is just taking Celebrex). The restriction on past use of glucosamine and chondroitin was relaxed and people who had taken these supplements were allowed to enter the study.
Unfortunately, since the effect from these supplments can last for years, we would expect the results of the study to significantly underestimate the real benefit of the supplements (we wouldn't expect a change in people who were given glucosamine and/or chondroitin in the study if they have already been taking it).
Subjects who were enrolled in the study met the following criteria:
(1) aged 40 years or older
(2) have been diagnosed with osteoarthritis of the knee
(3) not have any other arthritis-like disease (like gout)
(4) be willing to travel to one of the centers where the study will take place.
(5) be willing to stop taking glucosamine or chondroitin (if currently taking either or both)
(6) be willing to take a COX-2 inhibitor drug (like Celebrex)
The results do prove the theory in The Arthritis Cure that the combination of Glucosamine + Chondroitin have a synergistic effect in patients that have significant symptoms.
Though the overall study is very technical and has many different outcomes to evaluate, keep in mind that we need to focus on those patients who were most severely affected by their disease (called the high WOMAC group). In the real world, these are the patients that are most likely to end up requiring drugs, physical therapy or surgery.
Patients who started out with low pain scores (also called the low WOMAC group) and the overall groups combined (which really mirrored the results in the low WOMAC group because the population consisted mostly of subjects who started with very little pain (78% low WOMAC pain scores) could get pain relief from almost any intervention - why choose the most toxic and expensive one (Celebrex?).
You may be surprised to learn that this study was highly biased and very likely to yield no results just based on the way it was designed... see the commentary section for full details...
Click to see the Full abstract results.
Origins and Steps < > Commentary by Dr. Theo