Review of the NIH glucosamine and chondroitin arthritis intervention primary trial study

knee arthritis glucosamine chondroitin

Below is a review of the NIH glucosamine/chondroitin arthritis intervention primary trial study

About the Study

What is the Glucosamine/chondroitin Arthritis Intervention Trial (GAIT)?

This trial tests the effects of the dietary supplements glucosamine hydrochloride (glucosamine) and sodium chondroitin sulfate (chondroitin sulfate) for the treatment of knee osteoarthritis.

The study tested whether glucosamine and chondroitin sulfate used separately or in combination reduced pain in participants with knee osteoarthritis.

The University of Utah, School of Medicine coordinated this study, which was conducted at 16 rheumatology research centers across the US. The study was funded by the National Center for Complementary and Integrative Health (NCCIH) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

What was the purpose of the study?

GAIT was designed to test how effective glucosamine and chondroitin sulfate are in reducing pain in 6 months over a large number of participants with knee osteoarthritis.

What was the basic design of the study?

Participants were randomly assigned to one of five treatment groups:

(1) glucosamine alone

(2) chondroitin sulfate alone

(3) glucosamine and chondroitin sulfate in combination

(4) celecoxib

(5) a placebo (an inactive substance that looks like the study substance).

Glucosamine, chondroitin sulfate and their combination were compared with a placebo to evaluate whether these substances significantly improve joint pain.

Celecoxib, which is a prescription non-steroidal anti-inflammatory drug (NSAID) used in the management of osteoarthritis pain, was also compared with placebo to validate the study design.

The study was double-blinded (the researchers and participants did not know which of the five treatment groups the participants were in) to reduce the chance of biased results. Participants received treatment for 24 weeks and were evaluated at the start of the study and at weeks 4, 8, 16, and 24. They were closely monitored for symptom improvement and for any adverse reactions to the study agents. X-rays documented each participant’s diagnosis of osteoarthritis. Participants were also stratified into two pain subgroups— 1,229 participants (78 percent) with mild pain and 354 participants (22 percent) with moderate-to-severe pain.

A positive response to treatment was defined as a 20% or greater reduction in pain at week 24 compared to the start of the study. All participants had the option to use up to 4000 mg of acetaminophen, as needed, to control pain from osteoarthritis throughout the study, except for the 24 hours prior to having their knee assessed. Acetaminophen use was low: on average, participants used fewer than two 500 mg tablets per day.

Study Background

What is osteoarthritis?

Osteoarthritis, also called degenerative joint disease, is the most common type of arthritis. It is caused by the breakdown of cartilage, which cushions the ends of bones within the joint, and can result in the bones rubbing against each other. Osteoarthritis is characterized by pain, joint damage, and limited motion. The disease generally occurs late in life, and most commonly affects the hands and large weight-bearing joints, such as the knees, ankles and hips.

What are glucosamine and chondroitin sulfate?

Glucosamine and chondroitin sulfate are natural substances found in and around the cells of cartilage. Glucosamine is an amino sugar that the body produces and distributes in cartilage and other connective tissue, and chondroitin sulfate is a complex carbohydrate that helps cartilage retain water. In Australia, glucosamine and chondroitin sulfate are commonly sold as dietary supplements.

What is celecoxib?

Celecoxib (brand name Celebrex) is a COX-2 inhibitor, a type of nonsteroidal anti-inflammatory drug (NSAID).

What doses were used for the various treatments?

The doses used in GAIT were based on the doses seen in the prevailing scientific literature.

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

How many people participated in the study and who were they?

1,583 people participated in the study. People age 40 or older with knee pain and documented x-ray evidence of osteoarthritis were eligible to participate. Participants could not have used glucosamine for 3 months and chondroitin sulfate for 6 months prior to entering the study. Mean age was 59 years and nearly two-thirds of participants were women. Of the 1,583 study participants, 78 percent (1,229) were in the mild pain subgroup and 22 percent (354) were in the moderate-to-severe pain subgroup.


Key Results

What were the key results of the study?

Researchers found that:

  • Participants taking Celecoxib, experienced statistically significant pain relief versus placebo—about 70% of those taking celecoxib had a 20% or greater reduction in pain versus about 60% for placebo.
  • Overall, there were no significant differences between the placebo and other treatments.
  • For a subset of participants with moderate-to-severe pain, glucosamine combined with chondroitin provided statistically significant pain relief compared with placebo—about 79% had a 20 percent or greater reduction in pain versus about 54 percent for placebo. According to the researchers, because of the small size of this subgroup these findings should be considered preliminary and need to be confirmed in further studies.
  • For participants in the mild pain subset, glucosamine and chondroitin sulfate together or alone did not provide statistically significant pain relief.


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