This study, totaling $14 million will also determine whether the combination of these two substances is more effective than glucosamine or chondroitin alone. Only a few rather small studies have been published in the worldwide literature, to-date," according to Stephen E. Straus, M.D., NCCAM Director. "Those short-term, controlled clinical trials suggested that, glucosamine is effective in relieving pain and increasing range of motion in patients with osteoarthritis. This major new study will provide compelling answers about the safety and effectiveness of glucosamine and/or chondroitin, to the nearly 40 million Americans who suffer with osteoarthritis," Dr. Straus added.

Since the contract was awarded, protocol development has been completed so that the study — now called the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), will proceed. The study investigators held a "kick-off" meeting September 27-29, 2000.

The ambitious study will be a 24 week, placebo-controlled, parallel, double blind, five-arm clinical trial. A total of 1588 individuals will be enrolled in the study at thirteen clinical centers. The efficacy of glucosamine alone, chondroitin alone, and the combination of glucosamine and chondroitin will be compared to placebo in treating knee pain of osteoarthritis (OA). Moreover, in order to verify that the study is able to detect significant treatment effects, celecoxib-an established effective conventional treatment for OA will also be compared to placebo. Patients will be able to take acetaminophen if they experience severe pain.

The study will be conducted in three phases. Phase I of the study has already been completed. This phase involved refining the study design, hiring personnel, developing operating policies and procedures, testing the electronic data entry system, obtaining local Institute Review Board (IRB) approvals and securing the Investigational New Drug (IND) exemption for the study from the Food and Drug Administration. Phase II is the enrollment and treatment phase, which will take approximately 33 months. During this phase patients will be recruited and evaluated, study data will be checked for errors and completeness, and reports will be prepared on patient recruitment, the status of data collection, and quality control. Phase III is expected to last 6 months, which will include data clean-up, analysis and preparation of the final report due in March 2005.

To thoroughly evaluate whether these substances impact the progression of knee OA, an additional study or "sub-study" has been added to the primary GAIT trial. In this sub-study, approximately one-half of patients enrolled in the primary GAIT trial will receive blinded treatment (whereby patients do not know the specific treatment they receive) for an additional eighteen months. Specially positioned knee radiographs will be obtained at the beginning of the study and after one and two years of treatment. These films will be compared and evaluated for any structural change among the five groups. Two-year clinical efficacy and safety data will also be collected. This sub-study is jointly funded by NCCAM and NIAMS.

Daniel O. Clegg, M.D, Professor of Medicine and Chief of the Division of Rheumatology, University of Utah School of Medicine, will direct the coordinating center, which will oversee the research, patient recruitment, and data collection efforts of thirteen study centers across the country.

The participating 13 study centers and contact numbers for study coordinators are as follows:

• University of Alabama at Birmingham, Birmingham AL (Larry W. Moreland, M.D.)
  Melinda Robertson (205) 934-7423

• Cedars-Sinai Medical Center, Los Angeles, CA (Michael Weisman, M.D.)
  Carol Joseph (310) 358-5757

• University of California, San Francisco, San Francisco, CA (Nancy Lane, M.D.)
  Rosita Stuart-Thiessen (415) 206-8644

• Indiana University, Indianapolis, IN (John Bradley, M.D.)
  Heather Countryman (317) 278-0555

• Arthritis Research Center Foundation, Wichita, KS (Frederick Wolfe, M.D.)
  Nancy Flowers (315) 263-2125

• Hospital For Joint Diseases, New York, NY (Clifton Bingham, III, M.D.)
  Vivian Abellana (212) 598-6650

• Case Western Reserve University, Cleveland, OH (Michele Hooper, M.D.)
  Traci Tomaro (216) 844-5253

• University of Pennsylvania, Philadelphia, PA (H. Ralph Schumacher, Jr., M.D.)
  Allison Van Dyke (215) 823-4480

• Arthritis Consultation Center at Presbyterian Hospital of Dallas, Dallas, TX (John Cush, M.D.)
  Emma Barnboym (214) 345-8067

• University of Pittsburgh, Pittsburgh, PA (Susan Manzi, M.D.)
  Michele Pauli (412) 692-4269

• University of Utah, Salt Lake City, UT (Christopher Jackson, M.D.)
  Sheldon Smith (801) 581-4911

• Virginia Mason Research Center, Seattle, WA (Daniel Furst, M.D.)
  Eching Voon (206) 223-6836 extension 2

• University of Nebraska Medical Center, Omaha, NE (James O'Dell, M.D.)
  Gail Paulsen (402) 559-4873

The Biostatistical Center is located at the VA Hospital, Hines, IL (Domenic Reda, M.S.), and The Pharmacy Center at the VA Medical Center, Albuquerque, NM (Carol Fye, R.Ph., M.S.) will also be involved in the study.

The glucosamine hydrochloride used in this study is manufactured by Pfanstiehl Laboratories located in Waukegan, IL and donated by Wilke Resources. The chondroitin sulfate is manufactured and donated by Bioiberica, S.A. located in Barcelona, Spain. Open-label acetaminophen 500mg capsules, donated by McNeil Consumer Healthcare, will also be provided to each center.

For information regarding patient recruitment, please contact the study center closest to you.