Ferritin and Iron Burden in SAH sIRB

NCT03754725 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PRO00110138
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

Ruptured cerebral aneurysms lead to subarachnoid hemorrhage (SAH),that has a high morbidity and mortality rate, the severity of which is predicted by the "Hunt-Hess grade" (HHG). SAH leads to iron (Fe) and hemoglobin (Hb) accumulation in the brain, which is toxic for neurons. Ferritin (iron reported in the brian) and iron overload leads to brain atrophy, specifically in the mesial temporal lobe (hippocampus, impairing patients' cognition. It is estimated that 50% of survivors have cognitive deficits. Most of the survivors of SAH could not return to work. Iron chelation therapy has been recently gaining ground as a therapeutic intervention in intraparenchymal hemorrhage and in SAH. However, there has not been any study that assess the iron deposition in the brain and the level of ferritin in the cerebrospinal fluid of SAH patients. The investigators propose to conduct a randomized trial using Deferiprone (oral chelating agent, "De") + standard of care versus standard of care in patient with SAH to:

1. 1.assess the level of ferritin (Ft) in CSF (CSF withdrawn from ventriculostomy tube),
2. 2.assess functional outcomes measured by the Montreal Cognitive Assessment (MoCA) score, a score used to assess the level of dementia, mainly in Alzheimer disease patients.
3. 3.quantify the the total iron deposition in the brain based on MRI

Conditions

SAH; Dementia

Keywords

Deferiprone

Outcome Measures

Primary Outcomes (1)

• Ferritin levels in cerebrospinal fluid

  Concentration of ferritin in the cerebrospinal fluid

  Day 10 from enrollment

Secondary Outcomes (8)

• Assess functional outcomes

  6 and 12 months from enrollment

• Change in hippocampus size

  On admission and at 6 and 12 months

• Change in amygdala measured size

  On admission and at 6 and 12 months

• Change in the amount of iron deposition in the brain

  On admission and at 6 and 12 months

• Indications of clinical vasospasm

  During hospitalization, up to 4 weeks

Study Arms (2)

Deferiprone

EXPERIMENTAL

This is the drug arm (deferiprone). Patients will receive oral deferiprone

Drug: Deferiprone pill; Behavioral: Montreal Cognitive Assessment

Control

PLACEBO COMPARATOR

this group will only receive the placebo (sugar pill)

Drug: placebo; Behavioral: Montreal Cognitive Assessment

Interventions

Deferiprone pill DRUG

1000 mg of deferiprone (oral) BID (15 mg/Kg)

Also known as: Ferritin

Deferiprone

placebo DRUG

patients will receive placebo orally

Control

Montreal Cognitive Assessment BEHAVIORAL

Neurocognitive assessment, lower score indicates lower cognitive level

Also known as: MoCA

Control; Deferiprone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 and less than or equal to 75 years.
• Historical modified Rankin Scale Score (mRS) 0-1 (pre-subarachnoid hemorrhage onset).
• World Federation of Neurosurgical Societies SAH Scale (WFNS) grade less than or equal to 4, due to a spontaneous SAH attributed to a ruptured cerebral aneurysm. Initial WFNS grade may be determined at admission or enrollment, preferably after the patient's mental status has been optimized by resuscitation and interval treatment of hydrocephalus (i.e., placement of intraventricular catheter or lumbar puncture \[LP\]) or reversal/wearing-off of sedating medications used commonly during patient transfers and transport or procedure related anesthesia.
• Admission head CT showing modified Fisher grade 1-4 due to aneurysmal subarachnoid hemorrhage (aSAH) primarily in the supratentorial space. The Modified Fisher CT rating scale is: Grade 1 (minimal or diffuse thing SAH without intraventricular hemorrhage); Grade 2 (minimal or thin SAH with intraventricular hemorrhage), Grade 3 (thick cisternal clot without intraventricular hemorrhage), Grade 4 (thick cisternal clot with intraventricular hemorrhage).
• Location and pattern of the SAH must have the majority of the SAH in the supratentorial space caused by either an intradural anterior circulation aneurysm or a basilar apex/posterior circulation aneurysm with primarily supratentorial hemorrhage extension. Angiographic location of the aneurysm will be confirmed by catheter digital subtraction angiography usually obtained during the coil embolization procedure.
• Onset of symptoms of aSAH (ictus) occurred \< 24 hours prior to presentation at the treating facility.
• Initiation of aneurysm securement procedure occurred \< 48 hours from the ictus and less than 12 hours from admission to the treating facility.
• All aneurysm(s) suspected to be responsible for the hemorrhage or potentially responsible for the hemorrhage must be secured in the following manner prior to enrollment: endovascular Coil Embolization with a post-embolization Raymond-Roy Score of 1 (Complete) or 2 (Residual Neck).
• Ability to screen the patient and obtain head CT and CT perfusion on admission and follow after recovering from anesthesia following the aneurysm coiling procedure, the patient must remain a WFNS SAH grade less than or equal to 4 without evidence of a significant new focal neurological deficit including monoparesis / monoplegia, hemiparesis / hemiplegia, or receptive, expressive or global aphasia. New minor cranial nerve defect without any other new findings is permissible. If a national institute of health stroke scale (NIHSS) score was obtained prior to the aneurysm coiling procedure, a post-coiling (pre-enrollment) NIHSS score must not have increased by 4 points or more and Glasgow coma score must not be decreased by 2 points or less. The clinician should use their best clinical judgment as to whether a significant neurological decline has occurred due to the coiling procedure.
• Ability to obtain MRI for ischemic changes evaluation.
• Subject's Legally Authorized Representative (LAR) has provided written informed consent.

You may not qualify if:

• Angio-negative SAH.
• A likely hemorrhage event within several days prior to admission related hemorrhage ictus due to the increased risk of early vasospasm.
• Prior sentinel headache with negative CT or prior sentinel headache where the patient did not seek medical attention does not exclude the patient.
• Surgical clipping of the ruptured aneurysm or any non-ruptured aneurysm on the same admission prior to enrollment.
• SAH not caused by aneurysm rupture or aneurysm is identified to be traumatic, mycotic, blister or fusiform type by catheter Digital Subtraction Angiography (DSA).
• Any intracranial stent placement or non-coil intra-aneurysmal device (i.e., stent- assisted coiling with Neuroform, Enterprise, LVIS, LVIS Jr, Barrel Stent, Pulse Rider, LUNA, Medina or a similar device) where the stent device is implanted to treat the ruptured aneurysm and / or antiplatelet therapy is needed.
• Subject developed SAH-induced cardiac stunning prior to enrollment, with an ejection fraction\< 30%, or requiring intravenous medications for blood pressure maintenance.
• Concurrent significant intracranial pathology identified prior to enrollment, including but not limited to, Moyamoya disease, high suspicion or documented CNS vasculitis, severe fibromuscular dysplasia, arteriovenous malformation, arteriovenous fistula, significant cervical or intracranial atherosclerotic stenotic disease (greater or equal to 70%), or malignant brain tumor.
• Serious co-morbidities that could confound study results including but not limited to: Multiple Sclerosis, dementia, severe major depression, cancer likely to cause death in 2 years, multi-system organ failure, or any other conditions that could cause any degree of cognitive impairment.
• Immunosuppression therapy including chronic corticosteroid usage.
• Remote history of previous ruptured cerebral aneurysm.
• History of gastrointestinal hemorrhage or major systemic hemorrhage within 30 days, hemoglobin less than 8 g/dL, international normalized ratio greater than or equal to1.5, severe liver impairment, creatinine greater than 2.0 mg/dL, or estimated glomerular filtration rate less than 60 ml/min.
• Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days.
• Currently pregnant.
• Contraindication for MRI.

Sponsors & Collaborators

• Duke University: lead

Study Sites (2)

Univesity of Iowa Hospital and Clinics

Iowa City, Iowa, 52242, United States

ACTIVE NOT RECRUITING

Duke University Health System

Durham, North Carolina, 27710, United States

RECRUITING

Related Publications (1)

• Van der Loo LE, Aquarius R, Teernstra O, Klijn K, Menovsky T, van Dijk JMC, Bartels R, Boogaarts HD. Iron chelators for acute stroke. Cochrane Database Syst Rev. 2020 Nov 24;11(11):CD009280. doi: 10.1002/14651858.CD009280.pub3.

  PMID: 33236783 DERIVED

MeSH Terms

Conditions

Dementia

Interventions

Deferiprone; Ferritins; Mental Status and Dementia Tests

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyridones; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Iron-Binding Proteins; Carrier Proteins; Proteins; Amino Acids, Peptides, and Proteins; Metalloproteins; Neuropsychological Tests; Psychological Tests; Behavioral Disciplines and Activities

Study Officials

• David Hasan, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

David Hasan, MD

CONTACT

919-681-2512; david.hasan@duke.edu

Beth Perry, RN

CONTACT

919-681-2695; beth.perry@duke.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2018
• First Posted: November 27, 2018
• Study Start: October 1, 2020
• Primary Completion: April 30, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)