Media Contact: Betsy Boyd-Flynn
Embargoed For Release at 5:30 pm PT, Sunday Nov. 13, 2005
GLUCOSAMINE AND CHONDROITIN SULFATE MAY BE USEFUL FOR PATIENTS WITH
MODERATE TO SEVERE PAIN FROM KNEE OSTEOARTHRITIS
SAN DIEGO, CALIFORNIA – Glucosamine and chondroitin sulfate may be an
effective combination in reducing pain associated with osteoarthritis
of the knee, according to research presented this week at the American
College of Rheumatology Annual Scientific Meeting in San Diego, California.
Glucosamine is an amino sugar naturally produced by the body and widely
distributed to the connective tissues, including cartilage. The body also
produces chondroitin sulfate, a complex carbohydrate molecule which, among
its other roles, helps retain water in cartilage. Over the past 25 years,
oral glucosamine and chondroitin sulfate, derived from animal products,
have become popular dietary supplements with patients attempting to combat
the cartilage wear and tear associated with osteoarthritis. The precise
biologic mechanisms that enable oral supplements to emulate the body's
natural products, however, remain undefined.
GAIT (The Glucosamine/Chondroitin Arthritis Intervention Trial) funded by the National Institutes of Health, was designed to rigorously assess the effectiveness and safety of these supplements
when taken separately or in combination. Almost 1,600 patients with painful
knee osteoarthritis were recruited from 16 U.S. academic rheumatology
centers for the study. The patients, who had experienced significant knee
pain for more than six months and had x-ray evidence of knee osteoarthritis,
were evaluated at the beginning of the study, and at weeks 4, 8, 16 and
24. Each was randomly assigned to receive glucosamine hydrochloride, sodium
chondroitin sulfate, both supplements, celecoxib, or placebo therapy and
allowed up to 4,000 mg daily of acetaminophen. The primary outcome measure
was a 20 percent improvement in knee pain by week 24.
“As expected, celecoxib improved knee pain in patients with osteoarthritis.
For the study as a whole, the supplements were not shown to be effective;
however, an exploratory analysis suggested that the combination of glucosamine
and chondroitin sulfate might be effective in osteoarthritis patients
who had moderate to severe knee pain,” stated Daniel O. Clegg, MD, Chief,
Division of Rheumatology, University of Utah School of Medicine, Salt
Lake City, Utah. Adverse events that were seen in GAIT were generally
mild and evenly distributed across all groups. Dr. Clegg continued, “Given
the results of this study, patients might want to discuss treatment options
with their physicians.”
The American College of Rheumatology is the professional organization
for rheumatologists and health professionals who share a dedication
to healing, preventing disability and curing arthritis and related rheumatic
and musculoskeletal diseases. For more information on the ACR's
annual meeting, see www.rheumatology.org/annual.
Editor's Notes: Dr. Clegg will present this research during a scientific
session at the ACR Annual Scientific Meeting from 10:45 am-12:30pm PT
on Monday, November 14, 2005 in Ballroom 20 A-D of the San Diego Convention
Center. He will be available for media questions and briefing at 8:30
am PT on Tuesday, November 15, in Room 23 A of the Convention Center.
Presentation Number: 622
The Efficacy of Glucosamine and Chondroitin Sulfate in Patients
with Painful Knee Osteoarthritis (OA): The Glucosamine/chondroitin Arthritis
Daniel O. Clegg 1, Domenic J. Reda 2, Crystal L. Harris 3, Marguerite
A. Klein 4, for the GAIT Investigators. 1 University of Utah, Salt Lake
City, UT; 2 VACSP, Hines, IL; 3 VACSP, Albuquerque, NM; 4 NCCAM/NIH, Bethesda,
PURPOSE: Glucosamine (G) and chondroitin
sulfate (CS) are widely promoted to “reduce joint pain and provide support
for healthy cartilage and joint function.” GAIT was designed to rigorously
assess the efficacy and safety of these agents alone and in combination.
G and CS were required to meet pharmaceutical standards as GAIT was conducted
under an Investigational New Drug application.
METHODS: Patients were =40 years
of age with knee pain (WOMAC Pain 125-400 mm) of at least 6 months duration
and x-ray evidence of knee OA [Kellgren-Lawrence (KL) Grades 2 or 3].
Patients were randomly assigned double-blind to placebo (P); G(Glucosamine
HCl 500 mg) tid; Sodium CS 400 mg tid; G+CS at the above doses tid; or
celecoxib (CE) 200 mg daily. All patients were allowed up to 4000 mg daily
of acetaminophen (APAP) as rescue analgesia, except within 24 hours of
study visits. Allocation was stratified by Center and by WOMAC Pain severity
(125-300mm and 301-400mm). Patients were evaluated at baseline and weeks
4, 8, 16 and 24. The primary outcome measure was a 20% improvement from
baseline in WOMAC Pain at week 24. Adverse events were documented at each
visit. Analysis was based on intention-to-treat.
RESULTS: 3238 patients were screened
at 16 US academic rheumatology centers. 1583 were randomized and 1258
(80%) completed the study. Baseline characteristics were: mean age 58.6
years, BMI 31.7 kg/m 2 , OA symptoms 10 years, 64% female, summed mean
WOMAC Pain 236±73mm (206mm for 125-300mm stratum, 341mm for 301-400mm
stratum), 59% KL Grade 2, and 78% were in the 125-300mm WOMAC Pain stratum
and were evenly distributed across all arms.
The response rate for CE (70.1%) was higher than the response rate for
P (60.1%) in the primary outcome analysis of all patients (p=0.008). In
the 301-400 mm WOMAC pain stratum, the response rate for G+CS (79.2%)
was higher than P (54.3%) (p=0.002). Secondary outcomes in the 301-400
mm stratum, including 50% WOMAC Pain response, WOMAC Stiffness, WOMAC
Function, HAQ, patient assessments, and use of rescue APAP all demonstrated
changes consistent with the primary outcome. Adverse events were generally
mild and evenly distributed among the groups.
Response Rates by Treatment Group and Pain Stratum
WOMAC Pain 301-400mm
WOMAC Pain 125-300mm
** p= 0.008 CE vs. P
+ p= 0.09 G+CS vs. P
¶p = 0.06 CE vs. P
# p = 0.002 G+CS vs. P
* p= 0.04 CE vs. P
CONCLUSIONS : Combination G+CS is effective in treating
moderate to severe knee pain due to OA. The lack of response in patients
with mild pain may be due to a floor effect, limiting ability to detect
response. All study agents were well tolerated.
Disclosure: D.O. Clegg, Pfizer 2; McNeil 5; D.J.
Reda, None; C.L. Harris, None; M.A.