Diabetes clinical trials role

A number of inhibitors directed towards the active site of PKC have been developed [4]. Many of these have therapeutic potential and some are in clinical trials. The drug enzastaurin (LY317615) shows selectivity towards inhibiting PKC 3 and is currently in clinical trials for cancer. This drug has particular potential as a treatment for colon cancer because of the specific role ofPKC (311 in this disease (see above). A separate PKC (3 inhibitor, ruboxistaurin (LY333531) has been developed as a drug to treat the microvasculature complications of diabetes hyperactivation of both PKC (311 and PKC (31 contribute to diabetic retinopathy and microvasculature complications. 

PTKs have been implicated in the regulation of a variety of biological responses such as cell proliferation, migration, differentiation, and survival. They have been demonstrated to play significant roles in the development of many disease states, including immunodeficiency, atherosclerosis, psoriasis, osteoporosis, diabetes, and cancer. In recent clinical trials impressive antitumor effects of PTK inhibitors have been observed. In future, PTK inhibitors may therefore become important drugs for the treatment of specific cancers. 

At least four clinical candidates including GSK-256073 [112], MK-0354 [102], MK-1903 [113], and INCB-19062 [91], and one preclinical candidate MK-6892 [77] have been reported. Neither the structure of GSK-256073, nor the clinical data, has been reported. In Phase II clinical trials, neither GPR109A partial agonist MK-0354, nor the full agonist MK-1903 showed substantial lipoprotein effects, and both candidates were discontinued. INCB-19062 is targeted to a type II diabetes indication based upon the related role of FFA to insulin sensitization in type II diabetes, and the robust FFA lowering effect observed in a Phase I clinical trial devoid of FFA rebound. 

Subsequent studies in experimental animals have yielded provocative results. Resveratrol is known to extend the lifespan of a number of organisms from yeast to vertebrates. Resveratrol is also known to prevent or slow the progression of cancer, cardiovascular diseases, diabetes, inflammation, and ischemic injuries in experimental animals. In short, the suggestion that resveratrol in red wine may be responsible for favorable outcomes in human health is supported by a number of studies in experimental animals. However, the support is suggestive but certainly not definitive. Carefully controlled clinical trials in people will be required to establish the role, if any, of resveratrol or related small molecules in human health. Such clinical trials are currently underway. 

Dietary protein has long been thought to play a role in the progression of chronic renal disease, but clinical trials have not consistently shown that dietary protein restriction is beneticial. A meta-analysis including the Modification of Diet in Renal Disease (MDRD) Study, of 1413 patients from 1966 to 1994 showed that dietary protein restriction slows the progression of both diabetic and non-diabetic renal disease (see Klahr et al., 1994). It is advisable to restrict protein intake moderately to 1 g/kg daily. 

One danger is that because herbal medications are not regulated, few if any clinical trials are performed even for safety or efficacy. One example is bilberry. Bilberry fruit is used to treat diabetes and diabetic retinopathy. Although animal models support the antioxidant role in vasoprotection, no well-designed and conducted clinical trials exist.The antioxidant effect may have benefit in AMD, as well. The antioxidant efficacy in bilberry is likely due to the tannin content, which is also found in grapes. 

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