Infliximab Therapy for Dolichoectactic Vertebrobasilar Aneurysms
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorUniversity of California, San Francisco
About this trial
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
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Vertebral and/or basilar artery dolichoectactic aneurysm not amenable to microsurgical or endovascular treatment.
Age greater than 18 years at time of first study drug administration.
Disqualifiers
Use of an anti-TNF or other biologic medication (Including but not limited to abatacept, rituximab, or tocilizumab) within the previous 12 months.
The following laboratory parameters at the Screening visit: Neutropenia (absolute neutrophil count < 1,500/microliter; Thrombocytopenia (platelets < 100,000/ • Anemia (hemoglobin < 8 g/dL); Greater than or equal to 3 times the upper limit of normal (ULN) for either of the following liver function tests (LFTs): aspartate transaminase (AST) or alanine transaminase (ALT); Renal insufficiency (serum creatinine> 2.0 mg/dL)
Purified protein derivative (PPD) test of > 5 mm induration regardless of prior BacilleCalmette Guerin vaccine administration or positive QuantiFERON®-TB Gold In-Tube Test (QFT-G_IT) without documentation of completed treatment or evidence of ongoing treatment of latent tuberculosis (TB) for 30 days. Subjects with active TB infection are excluded.
History of positive PPD, positive QuantiFERON®-TB Gold In-Tube Test (QFT-G_IT), or chest x-ray findings indicative of prior TB infection, without documentation of either treatment for TB infection or chemoprophylaxis for TB exposure
Trial design
Design model
Single group
Treatments tested in this trial
Infliximab
DrugPlease see protocol for details.
Treatment groups
8 Participants
are divided into 1 treatment groupGroup A: Infliximab treatmentExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Reduction in aneurysm volume (ml)
Our primary outcome for assessing the effectiveness of the infliximab treatment will be the reduction in aneurysm volume over the treatment course based on the 0 and 12 month MR scans. DVB aneurysm volume will be assessed by review of standardized 1.5 mm slices in the axial plane. The contour of the aneurysm using time-of-flight MR angiography sequences will generate a cross-sectional area at each slice level. The volume will be estimated by summing the imputed volume of each slice. Standard T1- and T2-weighted sequences will also be obtained, as well as iron-sensitive sequencing.
Time frame
12 monthsSecondary outcomes
1
Aneurysm computational fluid dynamic (CFD) metrics: flow velocity (ml/sec)
The investigators will capture MR-based, quantitative changes in the aneurysm computational fluid dynamics (CFD) metrics including flow velocity post 12-month IV infliximab administration. The investigators will compare pre- and post-treatment flow velocities using baseline and interval MR angiographic data. Such data is important in predication of aneurysm growth.
Time frame
12 months2
Aneurysm computational fluid dynamic (CFD) metrics: shear stress (pascal)
The investigators will capture MR-based, quantitative changes in the aneurysm computational fluid dynamics (CFD) metrics including wall shear stress post 12-month IV infliximab administration. The investigators will compare pre- and post-treatment CFD metrics using baseline and interval MR angiographic data. Such data is important in predication of aneurysm growth.
Time frame
12 months3
Aneurysm computational fluid dynamic (CFD) metrics: oscillatory index (0 - 0.5)
The investigators will capture MR-based, quantitative changes in the aneurysm computational fluid dynamics (CFD) metrics including oscillatory shear (OSI) index post 12-month IV infliximab administration. The investigators will compare pre- and post-treatment CFD metrics using baseline and interval MR angiographic data. Such data is important in predication of aneurysm growth. OSI ranges from 0 to 0.5, where 0 describes a total unidirectional WSS and the latter a purely unsteady, oscillatory shear flow with a net amount of zero WSS. Areas of high OSI are predisposed to endothelial dysfunction.
Time frame
12 months4
Aneurysm wall enhancement (ratio of signal post:signal pre contrast)
Continued improvements in higher field MR imaging have generated series noting the ability to not only resolve aneurysmal wall enhancement, but also the presence of such findings to reliably predict aneurysm growth and correlate with symptomatic events. To perform wall enhancement, the patient will first be scanned at 3T/7T using T1 weighted 3D black blood MRI technique (SPACE). Gadolinium will be injected and a 3D isotropic, high-resolution first-pass contrast-enhanced MR angiogram (CEMRA) will be obtained; immediately following that a post-contrast SPACE will be acquired. Contrast enhancement of the vessel wall will be graded as 0-2 scale or quantified by an enhancement ratio (Signal-post/Sigal-pre). Wall thickness can be estimated by the full width half maximal (FWHM) of the line profile across the vessel wall.
Time frame
12 monthsSponsors and contacts
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Source ClinicalTrials.gov