RECRUITING

Ferritin and Iron Burden in SAH sIRB

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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. assess the level of ferritin (Ft) in CSF (CSF withdrawn from ventriculostomy tube), 2.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. quantify the the total iron deposition in the brain based on MRI

Official Title

A Phase 1/2a Exploratory Clinical Trial to Evaluate the Safety of Oral Deferiprone (14 Days) Including Its Effect on Decreasing the Content of Iron in Subjects With Aneurysmal Subarachnoid Hemorrhage (aSAH) sIRB

Quick Facts

Study Start:2020-10-01

Study Completion:2026-05-27

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT03754725

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age greater than or equal to 18 and less than or equal to 75 years. 2. Historical modified Rankin Scale Score (mRS) 0-1 (pre-subarachnoid hemorrhage onset). 3. 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. 4. 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). 5. 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. 6. Onset of symptoms of aSAH (ictus) occurred \< 24 hours prior to presentation at the treating facility. 7. Initiation of aneurysm securement procedure occurred \< 48 hours from the ictus and less than 12 hours from admission to the treating facility. 8. 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). 9. 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. 10. Ability to obtain MRI for ischemic changes evaluation. 11. Subject's Legally Authorized Representative (LAR) has provided written informed consent.	1. Angio-negative SAH. 2. A likely hemorrhage event within several days prior to admission related hemorrhage ictus due to the increased risk of early vasospasm. 3. Prior sentinel headache with negative CT or prior sentinel headache where the patient did not seek medical attention does not exclude the patient. 4. Surgical clipping of the ruptured aneurysm or any non-ruptured aneurysm on the same admission prior to enrollment. 5. SAH not caused by aneurysm rupture or aneurysm is identified to be traumatic, mycotic, blister or fusiform type by catheter Digital Subtraction Angiography (DSA). 6. 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. 7. Subject has remaining aneurysm(s) that are untreated and could reasonably be considered a possible alternate cause of the aSAH based on the observed bleeding pattern. Adequate treatment of these aneurysms by coiling embolization would result in the aneurysms no longer causing an exclusion. MRI may be used in some situations to determine that the associated aneurysms did not rupture based on lack of blood seen adjacent to the additional aneurysms. 8. Diagnosis of sepsis (systemic inflammatory response syndrome \[SIRS\] criteria plus the presence of known or suspected infection) or current documented active bacterial or viral infection prior to enrollment (Example: significant upper respiratory infection (URI), community-acquired pneumonia). A minor non-complicated community-acquired urinary tract infection (UTI) would not be an exclusion but should be treated promptly. 9. New parenchymal hemorrhage or new infarction larger the 15 milliliters in volume, or significant increased mass effect as seen on the post coiling pre-enrollment head CT when compared to baseline admission head CT. New hyperdensity on CT scan related to contrast staining is not an exclusion. 10. Subject developed SAH-induced cardiac stunning prior to enrollment, with an ejection fraction\< 30%, or requiring intravenous medications for blood pressure maintenance. 11. 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. 12. Known seizure or epilepsy disorder (diagnosed prior to this aSAH diagnosis) where anti-epileptic medication was previously taken by the patient or have been recommended to be taken by the patient. Childhood seizures that have resolved and no longer require treatment are not part of this exclusion criteria. 13. 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. 14. Immunosuppression therapy including chronic corticosteroid usage. 15. Remote history of previous ruptured cerebral aneurysm. 16. 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. 17. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days. 18. Currently pregnant. 19. Contraindication for MRI. 20. No hydrocephalus requiring EVD or LP. 21. Known hypersensitivity to Deferiprone or to any of the excipients in the formulation. 22. If endovascular treatment of their aneurysm requires adjunctive antiplatelet treatment. 23. Uncontrollable hypertension (\>180 systolic and/or \>110 diastolic) that is not correctable prior to enrollment.

Inclusion Criteria

Exclusion Criteria

1. Age greater than or equal to 18 and less than or equal to 75 years.
2. Historical modified Rankin Scale Score (mRS) 0-1 (pre-subarachnoid hemorrhage onset).
3. 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.
4. 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).
5. 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.
6. Onset of symptoms of aSAH (ictus) occurred \< 24 hours prior to presentation at the treating facility.
7. Initiation of aneurysm securement procedure occurred \< 48 hours from the ictus and less than 12 hours from admission to the treating facility.
8. 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).
9. 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.
10. Ability to obtain MRI for ischemic changes evaluation.
11. Subject's Legally Authorized Representative (LAR) has provided written informed consent.

1. Angio-negative SAH.
2. A likely hemorrhage event within several days prior to admission related hemorrhage ictus due to the increased risk of early vasospasm.
3. Prior sentinel headache with negative CT or prior sentinel headache where the patient did not seek medical attention does not exclude the patient.
4. Surgical clipping of the ruptured aneurysm or any non-ruptured aneurysm on the same admission prior to enrollment.
5. SAH not caused by aneurysm rupture or aneurysm is identified to be traumatic, mycotic, blister or fusiform type by catheter Digital Subtraction Angiography (DSA).
6. 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.
7. Subject has remaining aneurysm(s) that are untreated and could reasonably be considered a possible alternate cause of the aSAH based on the observed bleeding pattern. Adequate treatment of these aneurysms by coiling embolization would result in the aneurysms no longer causing an exclusion. MRI may be used in some situations to determine that the associated aneurysms did not rupture based on lack of blood seen adjacent to the additional aneurysms.
8. Diagnosis of sepsis (systemic inflammatory response syndrome \[SIRS\] criteria plus the presence of known or suspected infection) or current documented active bacterial or viral infection prior to enrollment (Example: significant upper respiratory infection (URI), community-acquired pneumonia). A minor non-complicated community-acquired urinary tract infection (UTI) would not be an exclusion but should be treated promptly.
9. New parenchymal hemorrhage or new infarction larger the 15 milliliters in volume, or significant increased mass effect as seen on the post coiling pre-enrollment head CT when compared to baseline admission head CT. New hyperdensity on CT scan related to contrast staining is not an exclusion.
10. Subject developed SAH-induced cardiac stunning prior to enrollment, with an ejection fraction\< 30%, or requiring intravenous medications for blood pressure maintenance.
11. 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.
12. Known seizure or epilepsy disorder (diagnosed prior to this aSAH diagnosis) where anti-epileptic medication was previously taken by the patient or have been recommended to be taken by the patient. Childhood seizures that have resolved and no longer require treatment are not part of this exclusion criteria.
13. 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.
14. Immunosuppression therapy including chronic corticosteroid usage.
15. Remote history of previous ruptured cerebral aneurysm.
16. 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.
17. Major surgery (including open femoral, aortic, or carotid surgery) within previous 30 days.
18. Currently pregnant.
19. Contraindication for MRI.
20. No hydrocephalus requiring EVD or LP.
21. Known hypersensitivity to Deferiprone or to any of the excipients in the formulation.
22. If endovascular treatment of their aneurysm requires adjunctive antiplatelet treatment.
23. Uncontrollable hypertension (\>180 systolic and/or \>110 diastolic) that is not correctable prior to enrollment.

Contacts and Locations

Study Contact

David Hasan, MD

CONTACT

919-681-2512

david.hasan@duke.edu

Beth Perry, RN

CONTACT

919-681-2695

beth.perry@duke.edu

Principal Investigator

David Hasan, MD

PRINCIPAL_INVESTIGATOR

Duke University

Study Locations (Sites)

Univesity of Iowa Hospital and Clinics

Iowa City, Iowa, 52242

United States

Duke University Health System

Durham, North Carolina, 27710

United States

Collaborators and Investigators

Sponsor: Duke University

David Hasan, MD, PRINCIPAL_INVESTIGATOR, Duke University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-10-01

Study Completion Date2026-05-27

Study Record Updates

Study Start Date2020-10-01

Study Completion Date2026-05-27

Terms related to this study

Keywords Provided by Researchers

Deferiprone

Additional Relevant MeSH Terms

SAH
Dementia