In a 2 2 factorial design , the effects of a diet-and-exercise program and of oral glucosamine sulfate ( double blind and placebo-controlled ) on the incidence of knee osteoarthritis were evaluated in a high-risk group of 407 middle-aged women with a body mass index 27 kg/m ( 2 ) without clinical signs of knee osteoarthritis at baseline ( ISRCTN 42823086 ) .