Atorvastatin for Cavernous Hemangioma

(AT CASH EPOC Trial)

Overseen By Agnieszka Stadnik, MS, CCRP

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must not be taking: Statins

Disqualifiers: Pregnancy, Renal disease, Liver dysfunction, Myopathy, others

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 24 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of atorvastatin, a cholesterol-lowering drug, on reducing iron buildup in the brain for people with cavernous hemangioma (CCM), a condition where blood vessel clusters form in the brain and can bleed. Participants will receive either atorvastatin or a placebo (a pill with no active ingredient) to determine if atorvastatin can lessen these iron deposits. The trial is ideal for individuals who experienced a symptomatic CCM bleed within the last year and can travel to the study site for regular visits. As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but it does exclude people who are currently treated with or likely to need treatment with certain prohibited medications. It's best to discuss your specific medications with the trial team.

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

Research has shown that atorvastatin is generally safe for use. Past studies have found no major safety issues with this drug, which reassures those considering participation in a trial involving atorvastatin. Some studies have even tested atorvastatin for treating rare diseases and found it safe. While atorvastatin is primarily known for lowering cholesterol, its use for other conditions has not revealed any major safety problems. This suggests it could be a safe choice for patients in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for cavernous hemangioma focus on managing symptoms or surgical removal. But atorvastatin, typically known for lowering cholesterol, is being explored for its potential to directly affect these blood vessel clusters. Researchers are excited because atorvastatin may reduce the size and number of these lesions by targeting underlying cellular mechanisms. This approach is different because it could offer a non-surgical, medication-based option that addresses the condition's root cause rather than just its symptoms.

What evidence suggests that atorvastatin might be an effective treatment for cavernous hemangioma?

Research has shown that atorvastatin, which participants in this trial may receive, may help prevent the growth and bleeding of cavernous hemangiomas, based on animal studies. These studies suggest that atorvastatin blocks a protein that reduces the development and bleeding of these lesions. However, one study found that atorvastatin did not significantly change iron buildup in brain lesions over two years compared to a placebo, the comparator in this trial. While early results are promising, more research is needed to confirm its effectiveness in humans for this condition. ^{1 2 3 5 6}

Who Is on the Research Team?

Daniel F Hanley, MD

Principal Investigator

Director, Division of Brain Injury Outcomes Service The Johns Hopkins Medical Institutions

Issam A Awad, MD

Principal Investigator

Director of Neurovascular Surgery University of Chicago Medicine and Biological Sciences

Are You a Good Fit for This Trial?

This trial is for individuals with a recent symptomatic bleed from Cavernous Hemangioma, who can visit the study site regularly. Excluded are those allergic to statins, with liver disease, substance abuse issues, serious illnesses not stable for 30 days, pregnant or likely to become so during the study, prior treatments on CCM lesion, MRI safety concerns (like metal implants), severe kidney issues or on certain medications.

Inclusion Criteria

My imaging tests show I have cerebral cavernous malformations.

I can travel to the study site for all required visits over 2 years.

I had a bleeding event due to CCM within the last year.

Exclusion Criteria

You are allergic or intolerant to gadolinium.

Inability or unwillingness of subject or legal guardian/representative to give written informed consent

I am prescribed statins for reasons not related to my heart condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive atorvastatin or placebo and are monitored for changes in CCM lesional iron deposition using MRI studies

24 months

Baseline, 12 months, and 24 months MRI evaluations

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atorvastatin
• Placebo

Trial Overview The AT CASH EPOC trial is testing whether atorvastatin reduces iron deposits in brain lesions caused by bleeding cavernous hemangiomas versus a placebo. It's randomized and double-blinded—meaning neither participants nor researchers know who gets the drug or placebo—and involves regular MRI scans over two years.

How Is the Trial Designed?

Group I: Treatment Active Control 1 Intervention

Atorvastatin 80mg OD (optimal dose). Treatment dose will be de-escalated to 40mg based on reported adverse events.

Group II: Placebo Placebo Group 1 Intervention

Identically looking capsules containing no active ingredient

Atorvastatin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in United States as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Canada as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia
• Prevention of cardiovascular disease

Approved in Japan as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in China as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Approved in Switzerland as Lipitor for:

• Hypercholesterolemia
• Mixed dyslipidemia
• Homozygous familial hypercholesterolemia

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Published Research Related to This Trial

Atorvastatin is a highly effective statin that significantly lowers LDL and total cholesterol levels, and it is the first statin proven to reduce triglycerides in patients with high triglyceride levels.

In addition to its cholesterol-lowering effects, atorvastatin has beneficial non-lipid effects, such as improving blood vessel function and reducing inflammation, although clinical trial evidence is still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin. Wierzbicki, AS.[2019]

Atorvastatin is generally well tolerated across various dosages, with only a slight increase in liver enzyme elevations at the highest dose (80 mg/day), but no significant risk of serious adverse events.

Unlike some other statins, atorvastatin has a low incidence of muscular toxicity and does not require dosage adjustments for patients with renal dysfunction, making it a safe option for older adults (65 years and older) as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atorvastatin: a safety and tolerability profile. Arca, M.[2021]

Atorvastatin effectively lowers elevated levels of LDL cholesterol and triglycerides in patients with various dyslipidemic disorders, showing tailored efficacy based on the specific lipid abnormalities present in each patient group.

The drug was well-tolerated among 231 patients in the study, with a safety profile comparable to other medications in the same class, indicating it is a safe option for managing cholesterol levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. Bakker-Arkema, RG., Best, J., Fayyad, R., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40120614/

Safety and efficacy of atorvastatin for rebleeding in cerebral ... Atorvastatin did not affect the mean change in lesional iron deposition on brain MRI over 2 years when compared with placebo.

2. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(25)00036-5/abstract

Safety and efficacy of atorvastatin for rebleeding in cerebral ... Atorvastatin was shown to prevent CCM growth and bleeding in animal models. We aimed to assess the safety and efficacy of atorvastatin on rebleeding in patients ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7054711/

Atorvastatin Treatment of Cavernous Angiomas with ... Preclinical studies show that atorvastatin blunts CA lesion development and hemorrhage through inhibiting RhoA kinase (ROCK), suggesting it may ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02603328

Study Details | NCT02603328 | Atorvastatin Treatment of ... Safety and efficacy of atorvastatin for rebleeding in cerebral cavernous malformations (AT CASH EPOC): a phase 1/2a, randomised placebo-controlled trial.

5. ahajournals.org ahajournals.org/doi/10.1161/STROKEAHA.123.044068

Trial Readiness of Cavernous Malformations With ... CONCLUSIONS: We report SH rate, functional, and patient-reported outcomes in trial-eligible cerebral cavernous malformation with SH patients.

6. alliancetocure.org alliancetocure.org/home/research-clinical-trials/completed-research-projects/atorvastatin-trial/

Atorvastatin Trial Atorvastatin was found to not affect symptomatic hemorrhage caused by CCM, but the trial paved the way for future CCM drug trials.