Sildenafil for Microvasculopathy in Chronic TBI

Part of paid clinical trials in Philadelphia, Pennsylvania.

Sponsor
University of Pennsylvania
Study ID
NCT05782244
Phase
PHASE2
Status
Recruiting
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Conditions

  • Traumatic Brain Injury

Eligibility Criteria

Sex
ALL
Age
18 Years - 70 Years
Healthy Volunteers
Not accepted

Interventions

  • Sildenafil Citrate low dose — DRUG
    Sildenafil citrate 20 mg, oral, TID
  • Placebo — DRUG
    Placebo, oral, TID
  • Sildenafil medium dose — DRUG
    Sildenafil 40 mg, oral, TID
  • Sildenafil high dose — DRUG
    Sildenafil 80 mg, oral, TID

Study Details

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.

Key Dates

Start date
Jul 2, 2024
Status verified
Dec 2025
Primary completion
Dec 31, 2027
Completion
Dec 31, 2027

Study Design

Enrollment
160 participants (estimated)
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Sildenafil citrate low dose
    Sildenafil citrate 20 mg, oral, TID
  • Placebo Comparator: Placebo
    Placebo, oral, TID
  • Active Comparator: Sildenafil citrate medium dose
    Sildenafil citrate 40 mg, oral, TID
  • Active Comparator: Sildenafil citrate high dose
    Sildenafil citrate 80 mg, oral, TID

Primary Outcome Measure

Optimal Dose [ Time Frame: Assessed at baseline visit ]

Central Contacts

Locations (1)

FacilityCityStateZIPSite coordinators
University of PennsylvaniaPhiladelphiaPennsylvania19104
Ramon Diaz-Arrastia, MD, PhD
[email protected]
Ramon Diaz-Arrastia, MD, PhD (PRINCIPAL_INVESTIGATOR)

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By research site
University of Pennsylvania· Philadelphia, PA

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