What is osteoarthritis? What are glucosamine and chondroitin sulfate?

Glucosamine / chondroitin Arthritis Intervention Trial
Primary and subsidiary findings
Glucosamine / chondroitin Arthritis Intervention Trial were more randomized, placebo-controlled study conducted in several locations throughout the United States.
study, which examined whether glucosamine and / or chondroitin can heal the pain of knee osteoarthritis.
ancillary or supplementary study, we examined whether dietary supplements can reduce the structural damage of knee osteoarthritis.
Primary GAIT Results: February 2006
Researchers led by rheumatologist Daniel O. Clegg, MD, University of Utah School of Medicine, conducted a 4-year primary GAIT study at 16 sites. The results, published in the New England Journal of Medicine, February 22, 2006, showed that the popular dietary supplement combination of glucosamine plus chondroitin sulfate did not provide significant relief from osteoarthritis more to all participants. However, a smaller subgroup of study participants with moderate to severe pain showed significant relief with the combined supplements.

What is the Glucosamine / chondroitin Arthritis Intervention Trial
Gait first large-scale multicenter clinical study in the United States to test the impact of dietary supplements containing glucosamine hydrochloride (glucosamine) and sodium chondroitin sulfate (chondroitin sulfate) for treatment of knee osteoarthritis. The study tested whether glucosamine and chondroitin sulfate used separately or in combination reduced pain in participants with knee osteoarthritis.
Previous studies in the medical literature had conflicting results on the effectiveness of glucosamine and chondroitin sulfate for treating osteoarthritis. GAIT was designed to test short-term (6 months) effectiveness of glucosamine and chondroitin sulfate in reducing pain in a large number of participants with knee osteoarthritis.
What was the basic design study?
In the walk, participants were randomly assigned to one of five treatment groups: (1) glucosamine alone, (2) chondroitin sulfate alone, (3) glucosamine and chondroitin sulfate combined (4) celecoxib, or (5) placebo ( inactive substance that is similar to the study substance). Glucosamine and chondroitin sulfate and their combination compared with placebo to evaluate whether these substances significantly improve pain in the joints. Celecoxib, which is an effective medicine in the management of osteoarthritis pain, as compared to placebo to validate the study design.

To reduce the likelihood of biased results, the study was double blind-neither the researchers nor the participants knew which of the five treatment groups the participants were in. Participants received treatment within 24 weeks. Participants were evaluated at baseline and at 4 weeks, 8, 16 and 24 and closely monitor the improvement of their condition, as well as for any possible adverse reactions to the study agents. X-rays documented each participant in the diagnosis of osteoarthritis. Participants were also divided into two subgroups, over 1229 participants (78 percent) with mild and more than 354 participants (22 percent) with moderate to severe pain.

A positive response to treatment was defined as 20 percent or more reduction of more than 24 per week compared with the beginning of the study. All participants had the opportunity to use up to 4000 mg of paracetamol, if necessary, to control pain from osteoarthritis throughout the study, except for 24 hours prior to the knees with their assessment. Paracetamol use was low: on average, participants used fewer than two tablets of 500 mg per day.

A positive response to treatment was defined as 20 percent or more reduction of more than 24 per week compared with the beginning of the study. All participants had the opportunity to use up to 4000 mg of paracetamol, if necessary, to control pain from osteoarthritis throughout the study, except for 24 hours prior to the knees with their assessment. Paracetamol use was low: on average, participants used fewer than two tablets of 500 mg per day.

What is osteoarthritis?
An estimated 27 million adults in the United States live with osteoarthritis, the most common form of arthritis. Osteoarthritis, also called degenerative joint disease, cause destruction of cartilage, which is the connective tissue between the ends of bones in the joint. Osteoarthritis is characterized by pain, joint damage and limited movement. The disease usually occurs in late life, and most commonly affects hands and weight bearing, such as the knee. Age, female gender, and obesity are risk factors for this condition.

What are glucosamine and chondroitin sulfate?
Glucosamine and chondroitin sulfate are natural substances found in and around the cells of cartilage. Glucosamine amino sugar that the body produces and distributes in cartilage and other connective tissue, and chondroitin sulfate complex carbohydrate that helps cartilage retain water. In the United States, glucosamine and chondroitin sulfate are sold as dietary supplements are regulated as foods rather than drugs.

What is celecoxib?
Celecoxib (brand Celebrex) is a type of nonsteroidal anti-inflammatory drugs (NSAIDs) called COX-2 inhibitor. Like traditional NSAIDs, celecoxib blocks the COX-2 in the body, stimulates inflammation. Unlike traditional NSAIDs, however, celecoxib does not block the action of COX-1 enzyme, which is known to protect the gastric mucosa. As a result, celecoxib reduces joint pain and inflammation with reduced risk of gastrointestinal ulcers and bleeding. Recent reports have linked the possible side effects of the cardiovascular system to the COX-2 inhibitors. Although the walk is not designed to study the safety celecoxib, participants were observed for adverse events and no increase in such side effects were observed.

What doses were used for different treatments?
Doses in gait was based on the doses seen in the current scientific literature.

Glucosamine alone: 1500 mg per day given as 500 mg three times a day
Chondroitin sulfate alone: 1200 mg per day given as 400 mg three times a day
Glucosamine plus chondroitin sulfate combined: same doses of 1500 mg and 1200 mg per day
Celecoxib: 200 mg per day
Acetaminophen: participants were allowed to receive up to 4000 mg (500 mg tablets) a day to control pain, except for 24 hours before the pain were evaluated.

The researchers concluded that:

Participants taking the positive control, celecoxib, experienced statistically significant pain relief compared with placebo, about 70 percent of those taking celecoxib had 20 percent or more reduction in pain compared with about 60 percent of placebo.
In general, there were no significant differences between the other test procedures and placebo.
For a subset of participants with moderate to severe pain, glucosamine combined with chondroitin sulfate provided statistically significant pain relief compared with placebo, about 79 percent had 20 percent or more reduction in pain compared with about 54 percent of placebo. According to researchers, because of the small size of this subgroup, these data should be considered preliminary and must be confirmed in further studies.
For a subset of participants with a softer, glucosamine and chondroitin sulfate together or alone did not provide statistically significant pain relief.

Consumer Information and Next Steps
Should people with osteoarthritis use glucosamine and chondroitin sulfate?
People with osteoarthritis should work with their healthcare provider to develop a comprehensive plan for managing their arthritis pain: eat right, exercise, weight loss, and use proven pain medications. If people have moderate to severe pain, they should talk to your doctor about whether glucosamine plus chondroitin sulfate, a suitable treatment option.

Can U.S. consumers get glucosamine and chondroitin sulfate products used in gait?
Identical products may not be commercially available. GAIT was conducted under the Investigational New Drug application filed with the Food and Drug Administration (FDA). All products used in the study were developed for the study and subject to FDA pharmaceutical regulations. Products were evaluated and production of collaborative research A. Program Clinical Research Pharmacy, FDA-licensed clinical center pharmacy research. Glucosamine and chondroitin sulfate used were tested for purity, potency, quality and consistency between batches. Products were again to ensure stability throughout the study.

Is GAIT team to do further studies of glucosamine and chondroitin sulfate?
Yes. Original GAIT study to include additional or auxiliary, a study to assess whether these dietary supplements can reduce the structural damage of osteoarthritis of the knee. In sub-study, interested GAIT patients were given the opportunity to continue their original study treatment for another 18 months, a total of 2 years. At the end of sub-study, the team collected data on 581 knees. After evaluating the X-Ray data, the researchers concluded that glucosamine and chondroitin sulfate, together or separately, appear to fare no better than placebo in slowing loss of cartilage in osteoarthritis of the knee joint. Interpreting the results of the study was complicated, however, because participants taking placebo had less loss of cartilage, or joint space width, than predicted. Results were obtained in October 2008 issue of Arthritis & Rheumatism.