Clinical trials of propentofylline in vascular dementia

The neuroprotective glial cell modulator propentofylline has been used in c linical trials involving more than 800 patients with vascular dementia (VaD ). These data derive from two sources: a pooled group of VaD patients from four early phase III European trials, and a multinational European;Canadian phase III study (MN 305) that features a combined randomized withdrawal/de layed onset of progression design to evaluate the effect of propentofylline on disease progression. In the pooled studies, DSM-III-R criteria, Hachins ki Ischemia Scores, computed tomography (CT), and magnetic resonance imagin g (MRI) were used to select subjects with mild-to-moderate disease; in MN 3 05, National Institute of Neurological Disorders and Stroke/Association Int ernationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIR EN) criteria and neurologic examinations (including CT and MRI scans) were used to select patients with possible or probable VaD. The use of a central rater to assess cerebrovascular disease in neuroradiologic examinations fo r study MN 305 was considered to be a key feature for reducing the heteroge neity of the VaD patient population. In addition, the inclusion of patients with possible VaD in this trial greatly increased the number of eligible p atients; subgroup analyses revealed no substantial differences between pati ents with probable versus possible VaD? justifying their inclusion in the s tudy, VaD patients exhibited a more pronounced placebo response in global a ssessments compared with the Alzheimer disease population in a parallel stu dy. In addition, they experienced less deterioration over time with respect to cognitive and global assessments. Beneficial effects of propentofylline were consistently demonstrated in the domains of cognitive and global func tion fbr both VaD populations; however, no treatment benefits could be demo nstrated for activities of daily living, possibly due to factors relating t o the study population/design, the lack of a validated test instrument for such patients, the caregiver-related phenomenon of "tutoring" or the nature of the disease itself.