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Summary

for people ages 18 years and up (full criteria)
study started
estimated completion:

Description

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

Details

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.

Keywords

Aneurysm Stroke Vasculitis Tumor Necrosis Factor-alpha Necrosis Infliximab

Eligibility

You can join if…

Open to people ages 18 years and up

  1. Vertebral and/or basilar artery dolichoectactic aneurysm not amenable to microsurgical or endovascular treatment.
  2. Age greater than 18 years at time of first study drug administration.

You CAN'T join if...

  1. Use of an anti-TNF or other biologic medication (Including but not limited to abatacept, rituximab, or tocilizumab) within the previous 12 months.
  2. 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)
  3. 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.
  4. 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
  5. Presence of open leg ulcers
  6. Chronic or persistent infection including but not limited to human immunodeficiency virus [HIV], untreated hepatitis B, listeriosis, TB, or other opportunistic infection). Patients with hepatitis C but without evidence of cirrhosis or significant hepatic dysfunction will be considered for inclusion on a case-by-case basis as will patients with chronic hepatitis B on anti-viral therapy.
  7. 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
  8. Receipt of a live vaccine within 4 weeks prior to randomization
  9. 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
  10. . Any medical condition, which, in the opinion of the investigator, would put the subject at risk by participation in the protocol
  11. . 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.
  12. . Pregnant (all women of childbearing potential must have a negative serum pregnancy test) or breastfeeding
  13. . Any investigational agent within the earlier of 4 weeks or 5 half-lives prior to randomization
  14. . History of drug or alcohol abuse within 6 months prior to randomization
  15. . Known allergy or hypersensitivity to any study products
  16. . Any psychiatric disorder that prevents the subject from providing informed consent
  17. . Inability or unwillingness to follow the protocol.
  18. . Unable to undergo MR imaging.

Details

Status
not yet accepting patients
Start Date
Completion Date
(estimated)
Sponsor
University of California, San Francisco
ID
NCT02638701
Phase
Phase 1/2
Lead Scientist
Daniel L. Cooke
Study Type
Interventional
Last Updated
November 2016
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