Deferoxamine for Subarachnoid Hemorrhage

(DISH Trial)

Recruiting at 1 trial location

Overseen By Aditya Pandey, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Aditya S. Pandey, MD

Must not be taking: Antiplatelets, Anticoagulants, Iron supplements

Disqualifiers: Giant aneurysm, Severe anemia, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 days

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called Deferoxamine for individuals who have experienced an aneurysmal subarachnoid hemorrhage (aSAH), a potentially dangerous type of brain bleed. The researchers aim to determine if Deferoxamine can safely reduce brain swelling and damage by removing excess iron in the brain. Participants will receive either a low or high dose of Deferoxamine or a placebo and will be monitored for six months. This trial suits those who have had aSAH confirmed by imaging and have had their aneurysm treated but still require help managing the effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are using anti-platelet or anticoagulant drugs or taking iron supplements with more than 325 mg of ferrous iron.

Is there any evidence suggesting that Deferoxamine is likely to be safe for humans?

Research has shown that deferoxamine has been studied for treating brain bleeding. In earlier studies, deferoxamine helped with brain swelling and the absorption of bleeding. Researchers have also examined the safety of different doses. For example, doses of 32 mg/kg have been used without major safety issues. Another study found that doses above 16 mg/kg in animals led to better recovery after brain bleeding.

While deferoxamine remains under study, these findings suggest it is generally well-tolerated. However, the current trial is in an early stage, so researchers are still collecting safety data. Overall, previous studies provide a hopeful view of deferoxamine's safety for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for aSAH?

Unlike the standard treatments for subarachnoid hemorrhage, which typically include surgical interventions like clipping and endovascular coiling, Deferoxamine offers a unique approach by targeting iron accumulation in the brain. This drug works by chelating excess iron, potentially reducing oxidative stress and neuronal damage following a hemorrhage. Researchers are excited about Deferoxamine because its distinct mechanism could provide a non-invasive treatment option that addresses the underlying biochemical damage, offering hope for improved recovery outcomes.

What evidence suggests that Deferoxamine might be an effective treatment for subarachnoid hemorrhage?

Research has shown that Deferoxamine, a medication that binds to iron, can help reduce damage from iron in brain injuries. In earlier studies, Deferoxamine improved recovery in patients with brain bleeding by reducing brain swelling. Specifically, some studies found that patients were 2.7 times more likely to have a good recovery when treated with Deferoxamine. This trial will evaluate two different doses of Deferoxamine to determine its effectiveness in treating aneurysmal subarachnoid hemorrhage (aSAH), a condition where bleeding occurs around the brain. These findings suggest that Deferoxamine could be effective in this context. ^{2 6 7 8 9}

Who Is on the Research Team?

Aditya Pandey, MD

Principal Investigator

University of Michigan

Are You a Good Fit for This Trial?

This trial is for patients with a recent brain aneurysm bleed who were independent before the event, can start treatment within 24 hours, and have had their aneurysm secured. They must be able to give consent and not have severe kidney issues, hearing loss, low blood counts, or allergies to deferoxamine.

Inclusion Criteria

You have been diagnosed with a brain aneurysm using special imaging tests.

You need to have a Glasgow Coma Scale score of 7 or higher after having an External Ventricular Drain placed if it is needed.

Informed consent obtained by patient or legal authorized representative (LAR)

Exclusion Criteria

I have a significant disability, with difficulty in daily activities.

I have a serious lung condition or need home oxygen.

I have severe anemia or need blood transfusions often.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants are randomized to receive either Deferoxamine at one of two doses or placebo for the treatment of aSAH

3 days

Daily in-hospital visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive assessments and monitoring for delayed cerebral ischemia

6 months

Regular follow-up visits post-discharge

What Are the Treatments Tested in This Trial?

Interventions

• Deferoxamine
• Placebo

Trial Overview The study tests if Deferoxamine (DFO), which binds iron in the body to prevent damage from free radicals, is safe and effective for treating bleeding from a brain aneurysm. Participants will receive either DFO at two different doses or a placebo.

How Is the Trial Designed?

Group I: Deferoxamine lower dose Experimental Treatment 1 Intervention

Deferoxamine 32 Milligram Per Kilogram (mg/kg)

Group II: Deferoxamine higher dose Experimental Treatment 1 Intervention

Deferoxamine 48 mg/kg

Group III: Placebo Placebo Group 1 Intervention

normal saline

Deferoxamine is already approved in United States, European Union for the following indications:

Approved in United States as Desferal for:

• Acute Iron Poisoning
• Chronic Iron Overload

Approved in European Union as Desferal for:

• Iron overload
• Aluminum toxicity

Who Is Running the Clinical Trial?

Aditya S. Pandey, MD

Lead Sponsor

Trials

1

Recruited

120+

Michigan Medicine PKUHSC Joint Institute for Translational & Clinical Research

Collaborator

Trials

1

Recruited

120+

Published Research Related to This Trial

Intranasal administration of deferoxamine (DFO) significantly increases its concentration in the brain compared to intravenous delivery, achieving up to 200 times more targeted delivery to the cortex, which is crucial for treating stroke.

In animal studies, both pre-treatment and post-treatment with intranasal DFO reduced stroke damage by 55%, indicating its potential as an effective treatment and preventive measure for ischemic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intranasal deferoxamine provides increased brain exposure and significant protection in rat ischemic stroke. Hanson, LR., Roeytenberg, A., Martinez, PM., et al.[2021]

In a study of 84 pediatric patients treated with deferoxamine (DFO) for transfusional hemochromatosis, only 1.2% experienced ocular toxicity, indicating that such side effects are rare when regular ophthalmic screenings are conducted.

The single case of ocular toxicity was mild and reversible, suggesting that with proper monitoring and dose adjustments, the risks associated with DFO treatment can be effectively managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferoxamine-related ocular toxicity: incidence and outcome in a pediatric population. Baath, JS., Lam, WC., Kirby, M., et al.[2013]

Intracerebroventricular (ICV) administration of deferoxamine (DFX) after subarachnoid hemorrhage (SAH) significantly reduced neuronal damage and improved cognitive outcomes in a mouse model, demonstrating superior neuroprotection compared to systemic administration.

The neuroprotective effects of DFX are linked to the expression of heme oxygenase-1 (HO-1) in microglial/macrophages, suggesting that monitoring HO-1 levels in patients could help predict their response to DFX treatment for hemorrhagic stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heme oxygenase-1-mediated neuroprotection in subarachnoid hemorrhage via intracerebroventricular deferoxamine. LeBlanc, RH., Chen, R., Selim, MH., et al.[2018]

Iron chelation therapy, including deferoxamine (DFO), deferiprone (DFP), and deferasirox (DFX), is generally safe for young patients under 25 with hemoglobinopathies, based on safety data from 2040 patients across 34 studies.

While DFO shows minimal serious adverse effects at recommended doses, DFP and DFX can lead to rare but serious reactions, and all therapies have specific safety risks, including increased transaminases and gastrointestinal disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profiles of iron chelators in young patients with haemoglobinopathies. Botzenhardt, S., Li, N., Chan, EW., et al.[2017]

A multicenter phase-I study involving 20 patients with spontaneous intracerebral hemorrhage (ICH) demonstrated that intravenous infusions of deferoxamine mesylate (DFO) are feasible and well-tolerated, with only 10% of subjects discontinuing due to adverse events.

The study identified a maximum tolerated dose of 62 mg/kg per day, and while some patients experienced mild blood-pressure-lowering effects, the overall safety profile was acceptable, paving the way for future efficacy studies of DFO in ICH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Selim, M., Yeatts, S., Goldstein, JN., et al.[2021]

A Phase I study found that the iron chelator Deferoxamine Mesylate (DFO) is well-tolerated in patients with intracerebral hemorrhage (ICH) at doses up to 62 mg/kg/day, showing no increase in serious adverse events or mortality.

The ongoing Phase II trial will assess the efficacy of DFO in improving clinical outcomes in 324 ICH patients over 3 months, providing critical data on whether to proceed to a larger Phase III trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High dose deferoxamine in intracerebral hemorrhage (HI-DEF) trial: rationale, design, and methods. Yeatts, SD., Palesch, YY., Moy, CS., et al.[2021]

Deferoxamine (DFX) was found to effectively limit edema expansion and facilitate hematoma absorption within the first week after intracerebral hemorrhage (ICH) onset, based on a meta-analysis of 7 studies involving various patient outcomes.

However, DFX did not lead to improved neurological outcomes after 3 and 6 months, and it did not significantly increase the risk of serious adverse events, suggesting it may be safe but not necessarily effective for long-term recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deferoxamine in intracerebral hemorrhage: Systematic review and meta-analysis. Sun, T., Zhao, YY., Xiao, QX., et al.[2023]

Desferrioxamine mesylate (DFO) significantly reduced perihematomal edema and hematoma volume in patients with intracerebral hematoma (ICH) within 7 days of treatment, based on a meta-analysis of 5 randomized controlled trials involving 239 patients.

At 30 days post-treatment, DFO also led to a significant improvement in neurological function, as measured by the reduction in National Institute of Health Stroke Scale (NIHSS) scores, indicating its potential as an effective treatment for ICH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of desferrioxamine mesylate in intracerebral hematoma: a systemic review and meta-analysis. Zhao, K., Li, J., Zhang, Q., et al.[2022]

Deferoxamine (DFX) significantly reduced brain water content by 85.7% and improved neurobehavioral scores in animal models of intracerebral hemorrhage (ICH), indicating its potential efficacy as a treatment.

The most effective administration of DFX occurred 2-4 hours after ICH at doses of 10-50 mg/kg, suggesting a critical window for intervention, although further clinical trials are needed to confirm these findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of deferoxamine in animal models of intracerebral hemorrhage: a systematic review and stratified meta-analysis. Cui, HJ., He, HY., Yang, AL., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3932442/

High Dose Deferoxamine in Intracerebral Hemorrhage (Hi- ... We hypothesize that treatment with DFO could minimize neuronal injury and improve outcome in ICH patients. As a prelude to test this hypothesis, we conducted a ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S0303846723000501

Review article Deferoxamine in intracerebral hemorrhage We found that DFX was effective in hematoma absorption on day 7 after onset, but the difference was not significant on day 14. DFX could suppress edema ...

3. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.121.035421

Effect of Deferoxamine on Outcome According to Baseline ... The adjusted odds ratio for deferoxamine treatment effect on good outcome in patients with moderate HV at day-180 was 2.7 (95% CI, 1.13–6.27) ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-deferoxamine-for-patients-with-aneurysmal-subarachnoid-hemorrhage/

Study on Deferoxamine for Patients with Aneurysmal ... This clinical trial investigates the impact of Deferoxamine on recovery in patients with aneurysmal subarachnoid hemorrhage, monitoring new ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02175225?term=DESFERAL&rank=5

Study Details | NCT02175225 | Intracerebral Hemorrhage ... The investigators hypothesize that treatment with the iron chelator, Deferoxamine Mesylate , improves the outcome of patients with brain hemorrhage.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12062813/

Deferoxamine for Spontaneous Intracranial Hemorrhage Deferoxamine administration can, at least within a short timeframe, improve neurological and radiological parameters.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT00598572?term=AREA%5BInterventionSearch%5D(DEFEROXAMINE%20MESILATE)%20AND%20AREA%5BStudyType%5D(INTERVENTIONAL)&rank=3

Dose Finding and Safety Study of Deferoxamine in Patients ... Our main objectives are: 1) to evaluate the safety and tolerability of varying doses of DFO, by determining the treatment related adverse events, in patients ...

8. ahajournals.org ahajournals.org/doi/10.1161/strokeaha.111.617589

Safety and Tolerability of Deferoxamine Mesylate in ... Animal studies have shown that human-equivalent doses of DFO ≥16 mg/kg are associated with improved outcome after experimental ICH. Therefore, ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6494117/

Deferoxamine Mesylate in patients with intracerebral ... In conclusion, our results indicate that patients with ICH continue to improve past 90 days, and that treatment with DFO at 32 mg/kg/day for 3 ...