Clinical trials disease progression

For some of these diseases, such as hypertension and heart disease, drugs such as ACE inhibitors and beta-blockers are available for treatment. For some other diseases, such as Alzheimer s disease, more effective drugs have yet to be discovered. For stroke, two late stage (Phase III) trials of NXY-059 and desmoteplase failed to meet the trial criteria. Other clinical trials in progress for ischemic stroke are presented in Table 11.1. 

Pharmacogenomic studies are often carried out in the context of clinical trials which, by virtue of having both a treatment and placebo group, are able to assess the association between a gene and disease progression independent of therapy as well as interactive effects of genotypes and therapy on disease. Several of the phar-... 

If there is no evidence of interaction, and yet there is evidence of an association between genotype and disease progression, the SNP still may be useful. Identifying fast disease progressors up front may be a mechanism to enrich clinical trials, decreasing the time needed to reach progression-related endpoints. 

The above data demonstrate an important, possibly even critical role of oxidative stress in AD pathogenesis. Therefore, it is reasonable to suggest that antioxidant administration could be useful for the treatment of AD patients. Grundman [320] recently summarized the results of clinical trial, in which vitamin E was administrated to AD patients with moderately severe disease. It has been concluded that the treatment with vitamin E may delay and slow disease progress in these patients. 

Clinical trials have produced unequivocal evidence that ACE inhibitors improve symptoms, slow disease progression, and decrease mortality in patients with HF and reduced LVEF (stage C). These patients should receive ACE inhibitors unless contraindications are present. ACE inhibitors should also be used to prevent the development of HF in at-risk patients (i.e., stages A and B). 

There is overwhelming clinical trial evidence that certain /J-blockers slow disease progression, decrease hospitalizations, and reduce mortality in patients with HF. 

Natalizumab was approved by the U.S. FDA for the treatment of MS in November 2004, and is being evaluated in Phase 3 clinical trials for IBD and CD.105 Based on Phase 3 clinical trials in MS patients, natalizumab appeared to be safe, since an increased rate of infection was not observed after 1 year of treatment.106 The safety of combined treatment with immunosuppressants, other than short courses of corticosteroids, was not evaluated and was not recommended because of the potential for an increased risk of infections. Flowever, barely three months after its approval, natalizumab was voluntarily withdrawn from the MS market by its manufacturer and all ongoing clinical trials were suspended due to the occurrence of a rare neurological disease, progressive multifocal leukoencephalopathy (PML), in 3 out of approximately 3,000 patients enrolled in clinical trials (2 in MS and 1 in CD).107 108 109... 

In clinical trials, biomarkers are used to indicate a particular disease state and its progression. They may be used as surrogate markers in the evaluation of the effectiveness of a drug as representative of the natural endpoint such as survival rate or irreversible morbidity. 

---