Infliximab Therapy for Dolichoectactic Vertebrobasilar Aneurysms

NCT02638701 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 15-16893
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Aneurysm; Stroke; Vasculitis; Tumor Necrosis Factor-alpha

Outcome Measures

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.

  12 months

Secondary Outcomes (4)

• Aneurysm computational fluid dynamic (CFD) metrics: flow velocity (ml/sec)

  12 months

• Aneurysm computational fluid dynamic (CFD) metrics: shear stress (pascal)

  12 months

• Aneurysm computational fluid dynamic (CFD) metrics: oscillatory index (0 - 0.5)

  12 months

• Aneurysm wall enhancement (ratio of signal post:signal pre contrast)

  12 months

Study Arms (1)

Infliximab treatment

EXPERIMENTAL

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.

Drug: Infliximab

Interventions

Infliximab DRUG

Please see protocol for details.

Also known as: Remicade

Infliximab treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• Presence of open leg ulcers
• Active infection or severe infections requiring hospitalization or treatment with intravenous (IV) antibiotics, IV antivirals, or IV antifungals within 30 days prior to randomization, or oral antibiotics, oral antivirals, or oral antifungals within 14 days prior to randomization
• Receipt of a live vaccine within 4 weeks prior to randomization
• History of malignancy within the past 5 years other than treated localized carcinoma in situ of the cervix or adequately treated non-metastatic squamous or basal cell skin carcinoma
• Any medical condition, which, in the opinion of the investigator, would put the subject at risk by participation in the protocol
• Women of childbearing potential who are sexually active and who do not agree to practice one of the following methods of contraception during the duration of the study: condoms, sponge, foams, jellies, diaphragm or intrauterine device; oral or parenteral contraceptives for 2 months prior to study product administration; a vasectomized partner; abstinence.
• Pregnant (all women of childbearing potential must have a negative serum pregnancy test) or breastfeeding
• Any investigational agent within the earlier of 4 weeks or 5 half-lives prior to randomization
• History of drug or alcohol abuse within 6 months prior to randomization
• Known allergy or hypersensitivity to any study products
• Any psychiatric disorder that prevents the subject from providing informed consent

Sponsors & Collaborators

• University of California, San Francisco: lead

Study Sites (1)

UCSF Medical Center

San Francisco, California, 94143, United States

RECRUITING

Related Publications (7)

• Flemming KD, Wiebers DO, Brown RD Jr, Link MJ, Huston J 3rd, McClelland RL, Christianson TJ. The natural history of radiographically defined vertebrobasilar nonsaccular intracranial aneurysms. Cerebrovasc Dis. 2005;20(4):270-9. doi: 10.1159/000087710. Epub 2005 Aug 22.

  PMID: 16123548 BACKGROUND

• Mangrum WI, Huston J 3rd, Link MJ, Wiebers DO, McClelland RL, Christianson TJ, Flemming KD. Enlarging vertebrobasilar nonsaccular intracranial aneurysms: frequency, predictors, and clinical outcome of growth. J Neurosurg. 2005 Jan;102(1):72-9. doi: 10.3171/jns.2005.102.1.0072.

  PMID: 15658099 BACKGROUND

• Starke RM, Raper DM, Ding D, Chalouhi N, Owens GK, Hasan DM, Medel R, Dumont AS. Tumor necrosis factor-alpha modulates cerebral aneurysm formation and rupture. Transl Stroke Res. 2014 Apr;5(2):269-77. doi: 10.1007/s12975-013-0287-9. Epub 2013 Sep 20.

  PMID: 24323710 BACKGROUND

• Ferrante A, Giardina AR, Ciccia F, Parrinello G, Licata G, Avellone G, Giardina E, Impastato R, Triolo G. Long-term anti-tumour necrosis factor therapy reverses the progression of carotid intima-media thickness in female patients with active rheumatoid arthritis. Rheumatol Int. 2009 Dec;30(2):193-8. doi: 10.1007/s00296-009-0935-2.

  PMID: 19387646 BACKGROUND

• Del Porto F, Lagana B, Lai S, Nofroni I, Tinti F, Vitale M, Podesta E, Mitterhofer AP, D'Amelio R. Response to anti-tumour necrosis factor alpha blockade is associated with reduction of carotid intima-media thickness in patients with active rheumatoid arthritis. Rheumatology (Oxford). 2007 Jul;46(7):1111-5. doi: 10.1093/rheumatology/kem089. Epub 2007 Apr 20.

  PMID: 17449484 BACKGROUND

• Burns JC, Best BM, Mejias A, Mahony L, Fixler DE, Jafri HS, Melish ME, Jackson MA, Asmar BI, Lang DJ, Connor JD, Capparelli EV, Keen ML, Mamun K, Keenan GF, Ramilo O. Infliximab treatment of intravenous immunoglobulin-resistant Kawasaki disease. J Pediatr. 2008 Dec;153(6):833-8. doi: 10.1016/j.jpeds.2008.06.011. Epub 2008 Jul 30.

  PMID: 18672254 BACKGROUND

• Hasan DM, Chalouhi N, Jabbour P, Magnotta VA, Kung DK, Young WL. Imaging aspirin effect on macrophages in the wall of human cerebral aneurysms using ferumoxytol-enhanced MRI: preliminary results. J Neuroradiol. 2013 Jul;40(3):187-91. doi: 10.1016/j.neurad.2012.09.002. Epub 2013 Feb 18.

  PMID: 23428244 BACKGROUND

MeSH Terms

Conditions

Aneurysm; Stroke; Vasculitis

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Daniel L Cooke, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Daniel L Cooke, MD

CONTACT

415 353 1863; daniel.cooke@ucsf.edu

Jonathan Graf, MD

CONTACT

415 206 6647; jonathan.graf@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Radiology and Biomedical Imaging

Study Record Dates

• First Submitted: December 15, 2015
• First Posted: December 23, 2015
• Study Start: October 1, 2024
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: July 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)