July 1, 1998

A recently completed clinical trial study of glucosamine hydrochloride was completed at Mt. Sinai Hospital in Toronto. Here are the results of this study.

The bulk Glucosamine Hydrochloride used in this landmark study was supplied by Pfanstiehl Laboratories, the manufacturer of the glucosamine used in Glucosamine-ES. Pfanstiehl is a US manufacturer of high quality pharmaceutical ingredients and operates an FDA inspected, cGMP plant in Waukegan, IL. Pfanstiehl is also the only manufacturer registering a Drug Master File on Glucosamine HCl with the FDA.

The results of North America's first clinical trial studying glucosamine hydrochloride, an alternative treatment for osteoarthritis, was announced on June 22nd, 1998 at the 12th Panamerican Conference of Rheumatology. Dr. Joseph Houpt, Chief of Rheumatology and clinical investigator from Mount Sinai Hospital in Toronto, led the study that found a trend toward improved pain management among subjects treated with glucosamine hydrochloride.

"Until now, the information about glucosamine in North America has been unscientific and largely based on testimonials," said Dr. Houpt. "When we began to consider studying glucosamine two and a half years ago, no one was willing to even give it a serious scientific look." Dr. Houpt decided to study glucosamine hydrochloride because many of his patients reported a benefit from taking it. Recently, one of the world's foremost biomedical research centers in the United States, the National Institutes of Health, began the process to identify researchers who would be interested in conducting a study on glucosamine as a treatment for osteoarthritis.

The initial study1, by Dr. Houpt and his colleagues, was double-blind and placebo-controlled, and took place over a 10-week period, including a two week wash-out to ensure that other medications were out of the patients' systems. Participants were given either 500 mg of glucosamine hydrochloride or placebo three times daily in order to measure the effect of these agents on the pain of osteoarthritis. Patients were encouraged to use acetaminophen for pain as required. Forty-five patients received glucosamine hydrochloride, while 53 received a placebo. Study participants were selected due to osteoarthritis in their knee joint; their knees were examined four times over the 10-week period.

The greatest patient benefits were revealed in an analysis of their daily diaries. The patients were asked to note their level of pain compared to the previous day, and to the start of the trial, as well as how many tablets of acetaminophen they took.

"Those who took glucosamine hydrochloride appeared to have less painful days overall than the patients who took a placebo," said Dr. Houpt. "In addition, a clinical examination of the affected knees suggested an improvement in glucosamine hydrochloride takers, noted over the last four weeks of the study.' This is consistent with earlier European studies on glucosamine sulfate with respect to the time (4 weeks) and dosage (1,500 mg daily) necessary for glucosamine to have an demonstrable effect.

In the Canadian study, the knee joint was selected because it is often plagued by osteoarthritis. Osteoarthritis leads to pain, stiffness, and sometimes the inability to use or move a joint because a breakdown occurs in the cartilage that lines and protects it. The disease typically affects older adults over age 65; in Canada, approximately 2.7 million people suffer with osteoarthritis. In Dr. Houpt's study, subjects ranged from age 40 to 85, with an average age of 62.

Of particular interest also are the results of the WOMAC (University of Western Ontario McMaster Osteoarthritis Index) questionnaire which compares those patients on glucosamine HCl versus those on placebo. A total of 24 specific questions dealing with pain (5 questions), stiffness (2 questions) and function (17 questions) were asked of the participants two weeks before testing started, at the start of testing and eight weeks after the start of testing. The mean response for 23 out of 24 of the questions showed a significant improvement (reduced pain & stiffness and improved joint function) in the glucosamine group over those on placebo. For such a strongly positive response to occur randomly, the odds would be approximately 1 in 650,000.

Following the 10 week double-blind trial, all subjects were given a two month supply of open label glucosamine hydrochloride2. Patients were asked to report by telephone at 4 and 8 weeks after completion of the closed trial and 83 were subsequently telephone surveyed. In addition to checking on compliance, continued glucosamine use and NSAID or analgesic use, each patient was asked if they were better, the same, or worse with regard to pain and function at 4 weeks, 8 weeks and at the end of the open trial (13 weeks) compared to the end of the closed trial.

Of significant note, more patients felt better at 4 and 8 weeks (approximately 53%) than at the beginning of the open trial (only 36%). Even more impressively, 77% of the 83 respondents continued to use Glucosamine Hydrochloride after the end of the open study even though they had to purchase their own supply.

Both the closed and open trials clearly show that glucosamine can reduce pain and stiffness as well as improve joint function. They also show that we need to continue to evaluate not only glucosamine but also our method of testing the effects of this product. The interest now being shown by NIH (National Institutes of Health) in glucosamine and their active solicitation of researchers willing to pursue additional studies is a clear sign that glucosamine will emerge as an accepted treatment for osteoarthritis.

Papers to be published this year.

"Effect of Glucosamine Hydrochloride in the Treatment of Pain of Osteoarthritis of the Knee," J. B. Houpt, R. McMillan, D. Paget-Dellio, A. Russell & H. K. Gahunia, Rheumatic Disease Unit, Mount Sinai Hospital, University of Toronto, Toronto, Canada

"Open Trial of Glucosamine Hydrochloride in the Treatment of Pain of Osteoarthritis of the Knee," C. R. Wein, J. B. Houpt, R. McMillan, A. Russell & H. K. Gahunia, Rheumatic Disease Unit, Mount Sinai Hospital, University of Toronto, Toronto, Canada