Focal Cerebral Arteriopathy Steroid Trial

NCT06040255 | Enrolling By Invitation Phase 4 DMC FDA Drug

• 2 other identifiers: UH3NS1197024UH3NS119702-02
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This comparative effectiveness trial (CET) in children with suspected focal cerebral arteriopathy (FCA) presenting with arterial ischemic stroke (AIS) or transient ischemic attack (TIA) will compare the use of early corticosteroid treatment (Arm A) versus delayed/no corticosteroid treatment (Arm B). Delayed corticosteroid treatment is given only for those demonstrating disease progression and is initiated as soon as the progression is detected (at any time after randomization). All participants will also receive standard of care therapy (aspirin and supportive care). Sites will randomize participants 1:1 to Arm A or B. Participants will be enrolled and randomized as soon as possible after their stroke/TIA up until 96 hours following the initial stroke/TIA event.

Conditions

Pediatric Stroke; Arteriopathy; Arterial Ischemic Stroke

Keywords

FCA; Focal cerebral arteriopathy; Pediatric stroke; Arterial ischemic stroke

Outcome Measures

Primary Outcomes (1)

• Change in Focal Cerebral Arteriopathy Severity Score (FCASS)

  Change in FCASS from baseline to 1 month (1-month delta FCASS) measured centrally on MRA studies (performed on scanners with the same magnet strength). The FCASS is a novel ordinal scale designed and validated for the FOCAS and PASTA trials (Fullerton HJ, Stroke, 2018; Slalova, Eur J Paediatr Neurol, 2020) . The FCASS sums the severity of involvement of each of 5 different arterial segments that can be involved in FCA: (1) supraclinoid ICA (very common), (2) M1 segment of the MCA (very common), (3) M2 branches, (4) A1 segment of the ACA, (5) A2 branches of the ACA. The involvement of the ICA, M1, and A1 are scored on a scale of 0 to 4: 0=no involvement, 1=irregularity or banding without stenosis, 2=less than 50% stenosis, 3= 50% stenosis or greater), 4=complete occlusion. The M2 and A2 are scored: 0=no involvement, 1=irregularity, 3=stenosis, 4=complete occlusion (no option for 2).

  Baseline to one month

Secondary Outcomes (6)

• Focal Cerebral Arteriopathy Severity Score (FCASS) at 1 month (required)

  Baseline to 1 month

• Focal Cerebral Arteriopathy Severity Score (FCASS) at 1 month at 12 months (when imaging is available)

  Baseline to 12 months

• Relative infarct volume at 1 month (required)

  1 month after baseline

• Relative infarct volume at 12 months (when imaging is available)

  12 months after baseline

• Pediatric Stroke Outcome Measure (PSOM) at 6 months

  6 months after baseline

Study Arms (2)

Arm A

ACTIVE COMPARATOR

Treat all children with suspected FCA with corticosteroids as soon as the diagnosis is made.

Drug: methylprednisolone, prednisolone, prednisone

Arm B

ACTIVE COMPARATOR

Treat only the subset of children that develop evidence of FCA disease progression.

Drug: methylprednisolone, prednisolone, prednisone

Interventions

methylprednisolone, prednisolone, prednisone DRUG

Any generic or brand-name methylprednisolone at the appropriate dose may be used. Likewise, any generic or brand-name prednisolone, or prednisone, at the appropriate dose may be used.

Arm A; Arm B

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 1 year through 18 years at stroke/TIA ictus (ineligible as of 19th birthday).
• Acute arterial ischemic stroke (AIS) or transient ischemic attack (TIA) in prior 4 days (96 hours).
• AIS definition: neurological deficit with acute onset (including seizures) and acute infarct(s) corresponding to arterial territory(ies) on brain imaging.
• TIA definition: neurological deficit with acute onset (not including seizures) consistent with ischemia of an arterial territory(ies) but without acute infarction on brain imaging.
• a. Baseline imaging findings consistent with FCA: i. unilateral focal irregularity, banding, stenosis, wall thickening/enhancement, or occlusion of the distal internal carotid artery (ICA) and/or its proximal branches (A1, M1, posterior communicating artery, proximal PCA), OR ii. unilateral infarction in the territory of the lenticulostriate arteries with normal MRA.
• b. Ability to return at 1-month (±7 days) post-stroke for an MRI/MRA (non-contrast) on a scanner of the same magnet strength as baseline MRI/MRA.\*
• Consent to study procedures.
• A repeat baseline MRI/MRA can be performed as a research scan within 24 hours of enrollment if needed to meet this requirement.

You may not qualify if:

• Prior stroke.
• Another identified cause of stroke/TIA, other than FCA. (Intracranial dissection is considered a subtype of FCA and will be included if the patient is not predisposed to dissection for the reasons listed below.)
• Presence of childhood stroke risk factors (known to be present at the time of enrollment):
• Risk factors for arterial dissection: connective tissue disorder (e.g., Ehlers-Danlos type IV, Marfan syndrome, osteogenesis imperfect); severe head or neck trauma in the two weeks preceding AIS/TIA (defined as skull or cervical fracture, or an ICU admission for trauma).
• Risk factors for moyamoya: genetic disorder or syndrome that predisposes to moyamoya (e.g., trisomy 21, neurofibromatosis type 1, tuberous sclerosis, sickle cell anemia, MOPD type II, PHACE syndrome); prior cranial radiation therapy.
• Risk factors for secondary vasculitis or vasospasm: acute meningitis, systemic lupus erythematosus or other autoimmune disorder that can cause vasculitis, recent cocaine/amphetamine use (prior 7 days), recent subarachnoid hemorrhage (prior 14 days).
• Risk factors for cardioembolism: complex congenital heart disease; recent cardiac surgery or catheterization (prior week); endocarditis or other cardiac valve disease with vegetations; right-to-left cardiac shunting lesion with deep vein thrombosis (DVT) or a known thrombophilia.
• Baseline parenchymal imaging demonstrating remote or bilateral infarcts
• Vascular imaging demonstrating bilateral arteriopathy or moyamoya collaterals
• Contraindication to corticosteroid therapy (e.g., baseline immunosuppression, significant infection, etc.) as determined by the treating physicians.
• Current or recent (within prior week) treatment with corticosteroids.
• Pregnant, post-partum (within 6 months of childbirth), or nursing.

Sponsors & Collaborators

• University of California, San Francisco: lead
• University of Cincinnati: collaborator
• Medical University of South Carolina: collaborator
• M.D. Anderson Cancer Center: collaborator
• University of Colorado, Denver: collaborator
• University of Iowa: collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• American Heart Association: collaborator

Study Sites (1)

University of California San Francisco

San Francisco, California, 94158, United States

Location

Related Publications (13)

• Wintermark M, Hills NK, DeVeber GA, Barkovich AJ, Bernard TJ, Friedman NR, Mackay MT, Kirton A, Zhu G, Leiva-Salinas C, Hou Q, Fullerton HJ; VIPS Investigators. Clinical and Imaging Characteristics of Arteriopathy Subtypes in Children with Arterial Ischemic Stroke: Results of the VIPS Study. AJNR Am J Neuroradiol. 2017 Nov;38(11):2172-2179. doi: 10.3174/ajnr.A5376. Epub 2017 Oct 5.

  PMID: 28982784 BACKGROUND

• Fullerton HJ, Stence N, Hills NK, Jiang B, Amlie-Lefond C, Bernard TJ, Friedman NR, Ichord R, Mackay MT, Rafay MF, Chabrier S, Steinlin M, Elkind MSV, deVeber GA, Wintermark M; VIPS Investigators. Focal Cerebral Arteriopathy of Childhood: Novel Severity Score and Natural History. Stroke. 2018 Nov;49(11):2590-2596. doi: 10.1161/STROKEAHA.118.021556.

  PMID: 30355212 BACKGROUND

• Elkind MS, Hills NK, Glaser CA, Lo WD, Amlie-Lefond C, Dlamini N, Kneen R, Hod EA, Wintermark M, deVeber GA, Fullerton HJ; VIPS Investigators*. Herpesvirus Infections and Childhood Arterial Ischemic Stroke: Results of the VIPS Study. Circulation. 2016 Feb 23;133(8):732-41. doi: 10.1161/CIRCULATIONAHA.115.018595. Epub 2016 Jan 26.

  PMID: 26813104 BACKGROUND

• Steinlin M, Bigi S, Stojanovski B, Gajera J, Regenyi M, El-Koussy M, Mackay MT; Swiss NeuroPediatric Stroke Registry. Focal Cerebral Arteriopathy: Do Steroids Improve Outcome? Stroke. 2017 Sep;48(9):2375-2382. doi: 10.1161/STROKEAHA.117.016818. Epub 2017 Jul 21.

  PMID: 28733481 BACKGROUND

• Steinlin M, O'callaghan F, Mackay MT. Planning interventional trials in childhood arterial ischaemic stroke using a Delphi consensus process. Dev Med Child Neurol. 2017 Jul;59(7):713-718. doi: 10.1111/dmcn.13393. Epub 2017 Jan 25.

  PMID: 28121022 BACKGROUND

• Fullerton HJ, Hills NK, Elkind MS, Dowling MM, Wintermark M, Glaser CA, Tan M, Rivkin MJ, Titomanlio L, Barkovich AJ, deVeber GA; VIPS Investigators. Infection, vaccination, and childhood arterial ischemic stroke: Results of the VIPS study. Neurology. 2015 Oct 27;85(17):1459-66. doi: 10.1212/WNL.0000000000002065. Epub 2015 Sep 30.

  PMID: 26423434 BACKGROUND

• Lanthier S, Armstrong D, Domi T, deVeber G. Post-varicella arteriopathy of childhood: natural history of vascular stenosis. Neurology. 2005 Feb 22;64(4):660-3. doi: 10.1212/01.WNL.0000151851.66154.27.

  PMID: 15728288 BACKGROUND

• Chabrier S, Rodesch G, Lasjaunias P, Tardieu M, Landrieu P, Sebire G. Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke. J Child Neurol. 1998 Jan;13(1):27-32. doi: 10.1177/088307389801300105.

  PMID: 9477245 BACKGROUND

• Braun KP, Bulder MM, Chabrier S, Kirkham FJ, Uiterwaal CS, Tardieu M, Sebire G. The course and outcome of unilateral intracranial arteriopathy in 79 children with ischaemic stroke. Brain. 2009 Feb;132(Pt 2):544-57. doi: 10.1093/brain/awn313. Epub 2008 Nov 27.

  PMID: 19039009 BACKGROUND

• Slavova N, Fullerton HJ, Hills NK, Breiding PS, Mackay MT, Steinlin M. Validation of the focal cerebral arteriopathy severity score (FCASS) in a Swiss cohort: Correlation with infarct volume and outcome. Eur J Paediatr Neurol. 2020 Sep;28:58-63. doi: 10.1016/j.ejpn.2020.07.015. Epub 2020 Aug 4.

  PMID: 32826156 BACKGROUND

• Lo WD, Ichord RN, Dowling MM, Rafay M, Templeton J, Halperin A, Smith SE, Licht DJ, Moharir M, Askalan R, Deveber G; International Pediatric Stroke Study (IPSS) Investigators. The Pediatric Stroke Recurrence and Recovery Questionnaire: validation in a prospective cohort. Neurology. 2012 Aug 28;79(9):864-70. doi: 10.1212/WNL.0b013e318266fc9a. Epub 2012 Aug 15.

  PMID: 22895580 BACKGROUND

• Schechter T, Kirton A, Laughlin S, Pontigon AM, Finkelstein Y, MacGregor D, Chan A, deVeber G, Brandao LR. Safety of anticoagulants in children with arterial ischemic stroke. Blood. 2012 Jan 26;119(4):949-56. doi: 10.1182/blood-2011-06-361535. Epub 2011 Dec 7.

  PMID: 22160380 BACKGROUND

• Fullerton HJ, Hills NK, Chen H, Dlamini N, Stence NV, Wintermark M; VIPS II Investigators. Changing Management of Focal Cerebral Arteriopathy of Childhood From 2010 to 2022. Stroke. 2025 Jun;56(6):1460-1468. doi: 10.1161/STROKEAHA.124.050550. Epub 2025 May 12.

  PMID: 40351190 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Methylprednisolone; Prednisolone; Prednisone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Pregnadienediols

Study Officials

• Heather J Fullerton, MD, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Because corticosteroids cause significant behavioral effects in children, the local study investigators cannot be effectively blinded to the treatment; however, one of the study biostatisticians and all personnel reviewing neuroimaging as a part of the neuroimaging core will be blinded to Study Arm assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2023
• First Posted: September 15, 2023
• Study Start: October 1, 2023
• Primary Completion (Estimated): July 31, 2029
• Study Completion (Estimated): January 31, 2030
• Last Updated: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)