Infliximab Therapy for Dolichoectactic Vertebrobasilar Aneurysms

Not yet recruiting

Phase 1/2 Results N/A

Trial Description

Patients harboring dolichoectactic vertebrobasilar (DVB) aneurysms are at risk of suffering SAH, ischemic stroke, and/or brainstem compression and many patients are not offered invasive treatment due to the futility of existing surgical methods. Consequently, there is demand for development of medical therapy for DVB aneurysms

Detailed Description

Dolichoectatic vertebrobasilar (DVB) aneurysms are fusiform in geometry and often large (< 10 cm) in size limiting traditional microsurgical clipping or endovascular coiling strategies. Collectively, DVB aneurysms represent ≤ 0.01% of all aneurysms (~ 600 US) and, consequently, their study is limited to a few small series. Despite their rarity, the location and geometry of DVB aneurysms make surgical intervention, microsurgical or endovascular, nearly uniformly fatal. Therefore, most DVB aneurysms are observed providing greater insight into their natural history than many more surgically amenable aneurysms. One series noted 28% of patients manifesting any neurological deficit, ischemic or hemorrhagic, over a 4 year interval with an overall mortality rate of ~ 20%.
Tumor necrosis alpha (TNFα). From the many implicated genetic pathways in aneurysm formation, tumor necrosis alpha (TNFα) has been noted a pivotal actor. In pre-clinical studies, the ability to inhibit TNFα induction prevents aneurysm rupture and even aneurysm growth altogether. In humans, TNFα inhibitor therapy has proven effective for many types of vascular inflammation including carotid wall thickening in the setting of rheumatoid arthritis. Over 12- and 24-month intervals, others have demonstrated significant decreases in carotid intima-media thickness in patients taking the TNFα inhibitor, infliximab. Furthermore, infliximab therapy has proven effective in refractory Kawasaki's disease, a condition characterized by post-infectious coronary artery inflammation in children. There is also evidence that infliximab therapy is effective in treatment of IVIG-refractory Kawasaki's disease including regressing coronary aneurysms. Despite the multitude of agents and indications both on and off-label, TNFα inhibitor therapy has not been used for the treatment of brain aneurysm.

Conditions

Interventions

  • Infliximab Drug
    Other Names: Remicade
    ARM 1: Kind: Experimental
    Label: Infliximab treatment
    Description: Administer infliximab intravenously to patients with DVB aneurysms (3 mg/kg at 0, 3 and 7 weeks, then at 8-week intervals x 7) for a total of 12-months. Patients will undergo MR imaging at 0, 12, and 24-month time points.

Trial Design

  • Masking: Open Label
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Single Group Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Reduction in aneurysm volume (ml) 12 months No
Secondary Aneurysm computational fluid dynamic (CFD) metrics: flow velocity (ml/sec) 12 months No
Secondary Aneurysm computational fluid dynamic (CFD) metrics: shear stress (pascal) 12 months No
Secondary Aneurysm computational fluid dynamic (CFD) metrics: oscillatory index (0 - 0.5) 12 months No
Secondary Aneurysm wall enhancement (ratio of signal post:signal pre contrast) 12 months No

Sponsors