NCT05782244: CVR-TBI

Sildenafil for Microvasculopathy in Chronic TBI

Recruiting now Phase 2 Last updated 10 December 2025

What this trial tests

Phase 2 trial testing Sildenafil Citrate low dose in Traumatic Brain Injury in 160 participants. Currently enrolling.

Timeline

2 July 2024

Primary endpoint
31 December 2027

31 December 2027

Quick facts

Lead sponsor	University of Pennsylvania
Phase	Phase 2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	sequential
Masking	quadruple
Primary purpose	treatment
Enrollment	160
Start date	2 July 2024
Primary completion	31 December 2027
Estimated completion	31 December 2027
Sites	1 location across United States

Drugs / interventions tested

• Sildenafil Citrate low dose — full drug profile →
• Placebo
• Sildenafil medium dose — full drug profile →
• Sildenafil high dose — full drug profile →

Conditions studied

• Traumatic Brain Injury — all drugs for Traumatic Brain Injury →

Sponsor

University of Pennsylvania

Who can join

Adults 18 to 70, any sex, with Traumatic Brain Injury. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Traumatic Cerebral Vascular Injury (TCVI) is a common consequence of traumatic brain injury (TBI), including mild TBI (mTBI). TCVI is associated with poor recovery after TBI in animal models. TCVI can be measured non-invasively in humans, and therapies targeting TCVI are attractive candidates to ameliorate the consequences of TBI. Sildenafil potentiates nitric oxide (NO) dependent vasodilatation and is approved by the Food and Drug Administration (FDA) for the treatment of erectile dysfunction and primary pulmonary hypertension. In pre-clinical models of stroke, sildenafil improves cerebral blood flow (CBF), promotes, angiogenesis, neurogenesis and improves recovery. In an initial Phase 2a trial (NCT01762475) of sildenafil in patients with chronic moderate to severe TBI, the investigators found that low dose sildenafil (25 mg BID) therapy is safe and well tolerated, that a single dose of sildenafil 50 mg potentiates CVR in areas of the brain with dysfunctional endothelium, and that CVR is a reliable diagnostic marker of TCVI and has potential as a pharmacodynamic and predictive biomarker. In this proposal, the investigators will conduct a randomized clinical trial to determine the optimal PDE5 inhibitor dose to improve or normalize microvascular function (as measured by the change in CVR measurements before and after a single dose of sildenafil, or ΔCVR) using a range of sildenafil citrate doses: 20, 40, 80 mg) in chronic TBI patients. The investigators will also test the safety and tolerability of the same dose ranges of chronic (4-week) thrice daily sildenafil or placebo administration in chronic TBI patients and explore its effects on chronic symptoms and clinical outcomes.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Phosphodiesterase-5 (PDE-5) Inhibitors as Therapy for Cerebrovascular Dysfunction in Chronic Traumatic Brain Injury.
   Kalyani P, Lippa SM, Werner JK, Amyot F, et al · · 2023 · cited 4× · PMID 37697134 · DOI 10.1007/s13311-023-01430-z