Effects of pentoxifylline on cognitive deficits in cerebral small vessel disease: a prospective, randomized controlled, multi-center trial protocol

Cognitive impairment caused by white matter injury in cerebral small vessel disease (CSVD) is common among the elderly but currently lacks effective treatment. Pentoxifylline (PTX) is a nonselective phosphodiesterase inhibitor that exhibits protective effects in a variety of vascular diseases. Previous animal studies have revealed that PTX can alleviate cognitive impairment mediated by chronic ischemic white matter injury (white matter hyperintensity, WMH) and mitigate WMH progression. However, there is still a lack of clinical studies on whether pentoxifylline can improve cognitive dysfunction caused by cerebral small vessel disease. This trial was designed to evaluate the safety and efficacy of pentoxifylline in improving cognitive impairment caused by WMH in cerebral small vessel disease. A prospective, randomized controlled, open-label, multicenter clinical study will be conducted at 13 medical centers in China. Approximately 240 eligible patients will be randomly assigned in a 1:1 ratio to receive or without pentoxifylline (400 mg tablets twice daily) for 6 months, with a follow-up of 1–2 years. Both groups will receive basic treatments (controlling blood pressure, blood sugar, etc.). Randomization sequences will be computer-generated by a professional clinical statistician and stratified by participating centers. The primary outcome is the change in white matter hyperintensity (WMH) volume from baseline to 6 months. The secondary outcomes include changes in white matter hyperintensity (WMH) volume from baseline to 1 year and 2 years, changes in cognitive performance from baseline to follow-up assessments (6 months, 1 year and 2 years after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention. Safety outcomes are adverse events, adverse drug reactions, severe or life-threatening hemorrhage and the occurrence of complex cardiovascular and cerebrovascular events. ChiCTR, ChiCTR2300069867. Registered on 28 March 2023, ( https://www.chictr.org.cn/showproj.html?proj=192462ChiCTR-2300069867 ). Date: 14/12/2022