Glucosamine Questions & Answers

What is the National Institutes of Health (NIH) Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT)?

GAIT is the first multicenter clinical trial in the United States to test the effects of the dietary supplements glucosamine and chondroitin for treatment of knee osteoarthritis. The study will test whether glucosamine and chondroitin used separately or in combination are effective in reducing pain in patients with knee osteoarthritis. GAIT includes an additional study (or sub-study) that will assess whether glucosamine and chondroitin can reduce or halt the progression of knee osteoarthritis.

The University of Utah School of Medicine was awarded a contract to coordinate this study, which was conducted at 16 research centers across the United States. The National Center for Complementary and Alternative Medicine (NCCAM) and the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) are two components of the National Institutes of Health (NIH) that are responsible for initiating this study.

What was the purpose of the study?
Results of previous studies in the medical literature have yielded conflicting results on the effectiveness of glucosamine and chondroitin as treatments for osteoarthritis. This study tested the short-term (6 months) effectiveness of glucosamine and chondroitin in reducing pain in a large number of patients with knee osteoarthritis. The sub-study will also evaluate the impact of glucosamine and chondroitin on progression of knee osteoarthritis following an additional 18-month treatment regimen.

Why did NIH fund a study of glucosamine and chondroitin for osteoarthritis? On January 27, 1998, NCCAM held a meeting to discuss the need, rationale, and feasibility of conducting a Phase III study (a human study involving over 1,000 patients to test the efficacy, safety, and side effects of a substance[s]) of glucosamine and chondroitin for the treatment of knee osteoarthritis. Meeting participants included experts in osteoarthritis, alternative medicine, biostatistics and family practice, and staff of the NIH and the U.S. Food and Drug Administration. The group determined that there was a real and urgent public health need to test these agents in a rigorous way, and that current scientific data supported short-term testing of glucosamine and chondroitin for pain control and functional improvement of osteoarthritis.

What was the basic design of the study?
In this study, patients were randomly assigned to receive either (1) glucosamine alone, (2) chondroitin alone, (3) glucosamine and chondroitin in combination, (4) celecoxib (brand name Celebrex), or (5) a placebo (an inactive substance that looks like the study substance). Glucosamine and chondroitin and their combination were compared to a placebo to see if these substances significantly improve joint pain. Celecoxib, which is an established effective conventional treatment for osteoarthritis, was also compared to placebo to validate the study design.

To reduce the chance of biased results, double-blind research procedures were used to ensure that neither the researchers nor the patients knew to which of the five treatment groups the patients belonged. In the main or primary study, each patient was treated for 24 weeks. During this time, patients were evaluated at 4, 8, 16, and 24 week intervals and closely monitored for improvement of their symptoms as well as for any possible adverse reactions to the agents. Medical evaluations and x rays were used to document each patient's diagnosis. The primary outcome was measured as improvement in pain. All patients had the option to use acetaminophen (e.g., Tylenol), as required, to control severe pain from osteoarthritis throughout the clinical trial.

In the sub-study, which will evaluate the progression of knee osteoarthritis, about one-half of the patients enrolled in GAIT will receive blinded treatment for an additional 18 months. As in the primary study, patients will not know to which treatment group they are assigned. Researchers will compare x rays taken at the beginning of the study and after 1 and 2 years of treatment. Then they will compare and evaluate x rays from all sub-study participants to identify changes in the knee joints as a result of treatment.

How many patients participated in the study?
A total of 1,583 people were recruited for the study.

Who was eligible to participate in the study?
Patients over age 40 with knee pain and x-ray evidence of osteoarthritis were eligible to participate. People in the study must not have used glucosamine for 3 months and chondroitin for 6 months prior to entering the study.

Where was the study conducted?
The University of Utah School of Medicine, Salt Lake City, Utah, served as the coordinating study center and oversaw the research and patient recruitment efforts of the 16 study centers. The participating 16 study centers were:
A.. University of Alabama at Birmingham, Birmingham, AL
B.. University of Arizona, Tucson, AZ
C.. Cedars-Sinai Medical Center, Los Angeles, CA
D.. University of California Los Angeles, Los Angeles, CA
E.. University of California San Francisco, San Francisco, CA
F.. Northwestern University, Chicago, IL
G.. Indiana University, Indianapolis, IN
H.. The Arthritis Research and Clinical Centers, Wichita, KS
I.. University of Nebraska Medical Center, Omaha, NE
J.. Hospital For Joint Diseases, New York, NY
K.. Case Western Reserve University, North Beachwood, OH
L.. University of Pennsylvania, Philadelphia, PA
M.. University of Pittsburgh, Pittsburgh, PA
N.. Presbyterian Hospital of Dallas, Dallas, TX
O.. University of Utah, Salt Lake City, UT
P.. Virginia Mason Medical Center, Seattle, WA

What is Osteoarthritis?
An estimated 21 million adults in the United States live with osteoarthritis--one of the most common types of arthritis. Osteoarthritis, also called degenerative joint disease, is caused by the breakdown of cartilage, which is the connective tissue that cushions the ends of bones within the joint. It 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. Although the disease can impact several joints, the knees are often affected. Age, female gender, and obesity are risk factors for this condition.

What are glucosamine and chondroitin?
Glucosamine and chondroitin are natural substances found in and around the cells of cartilage. Researchers believe these substances may help in the repair and maintenance of cartilage. In addition, researchers believe that glucosamine inhibits inflammation and stimulates cartilage cell growth, while chondroitin provides cartilage with strength and resilience. Currently, glucosamine and chondroitin are classified as dietary supplements.

What is a dietary supplement?
A dietary supplement is a product (other than tobacco) intended to supplement the diet, which bears or contains one or more of the following dietary ingredients: a vitamin, mineral, amino acid, herb, or other botanical; is intended for ingestion in the form of a capsule, powder, softgel, or gelcap; and is not represented as a conventional food or as a sole item of a meal or the diet (as defined by the U.S. Dietary Supplement Health and Education Act, Oct. 25, 1994).

What is Celecoxib?
Celecoxib (brand name Celebrex) is a new type of nonsteroidal anti-inflammatory drug (NSAID), called a COX-2 inhibitor. Like traditional NSAIDS, celecoxib blocks the COX-2 enzyme in the body that stimulates inflammation. Unlike traditional NSAIDS, however, celecoxib does not block the action of COX-1 enzyme, which is known to protect the stomach lining. As a result, celecoxib reduces joint pain and inflammation with reduced risk of gastrointestinal ulceration and bleeding.