Phase 2 Randomized Controlled Trial of Sildenafil Citrate for Treatment of Cerebrovascular Dysfunction in Chronic Traumatic Brain Injury
Abstract
The failure of multiple clinical trials for traumatic brain injury (TBI) highlight the urgent need for biomarker-driven strategies to identify specific brain pathologies and provide an objective measure to monitor pharmacodynamics and evaluate therapeutic efficacy. This project builds on our Phase 2a study of a phosphodiesterase 5 (PDE5) inhibitor, sildenafil citrate, in chronic TBI (ClinicalTrials.gov NCT01762475). We demonstrated that: (1) CVR is decreased in patients with chronic TBI; (2) sildenafil improves CVR in these patients; and (3) 8-weektreatment with sildenafil citrate, at 25 mg twice daily, was well tolerated and associated with a trend towards clinical improvement. This Phase IIb trial will extend these findings by identifying the optimal effective and tolerated dose, fine tune study procedures and inclusion/exclusion criteria, and further assess the effect of sildenafil on post-TBI symptoms and cognitive function. Over the first year of this project we have completed all the regulatory requirements to launch the project, including IRB and OHRO approval, have hired and trained research staff, purchased investigational product and manufactured placebo tablets, finalized the protocol, manual of operations, analytical plan, and pharmacy manual.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2023
- Accession Number
- AD1219036
Entities
People
- Carol Moore
- Pamela Bonner
- Priyanka Kalyani
- Ramon Diaz-Arrastia
Organizations
- University of Pennsylvania