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

80 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if atorvastatin can help patients who had a recent brain bleed by reducing iron deposits in their brain. Atorvastatin has shown potential in reducing lesion development and hemorrhage in cerebral cavernous angiomas. The study will use MRI scans to measure changes over time.

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.

What data supports the effectiveness of the drug Atorvastatin for treating cavernous hemangioma?

Preclinical studies suggest that atorvastatin may help reduce the development and bleeding of cavernous angiomas by inhibiting a specific enzyme (RhoA kinase), which indicates it could be beneficial for patients with these lesions. ^{1 2 3 4 5}

Is atorvastatin safe for humans?

Atorvastatin, also known as Lipitor, is generally safe and well-tolerated in humans. It has a good safety profile, with a low incidence of muscle-related side effects and no significant impact on the liver or kidneys at typical doses. ^{6 7 8 9 10}

How does the drug atorvastatin differ from other treatments for cavernous hemangioma?

Atorvastatin is unique because it may help reduce the development and bleeding of cavernous hemangiomas by inhibiting a specific enzyme called RhoA kinase, which is not a common target in existing treatments for this condition. ^{1 5 11 12 13}

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Atorvastatin Treatment of Cavernous Angiomas with Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Regression of Macular Cavernous Hemangioma with Systemic Infliximab. [2019]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Impact of Long-Term Antithrombotic and Statin Therapy on the Clinical Outcome in Patients with Cavernous Malformations of the Central Nervous System: A Single-Center Case Series of 428 Patients. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

Familial cavernous hemangioma: An expanding ocular spectrum. [2015]

5. United States pubmed.ncbi.nlm.nih.gov

Combined HMG-COA reductase and prenylation inhibition in treatment of CCM. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Atorvastatin. [2019]

7. Ireland pubmed.ncbi.nlm.nih.gov

A brief review paper of the efficacy and safety of atorvastatin in early clinical trials. [2019]

8. England pubmed.ncbi.nlm.nih.gov

Atorvastatin is not cataractogenic in beagle dogs. [2019]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Atorvastatin: a safety and tolerability profile. [2021]

10. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Atorvastatin and diabetic vascular complications. [2019]

11. England pubmed.ncbi.nlm.nih.gov

The use of atorvastatin for chronic subdural haematoma: a retrospective cohort comparison study. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Bleeding Risk of Cerebral Cavernous Malformations in Patients on Statin and Antiplatelet Medication: A Cohort Study. [2023]

13. England pubmed.ncbi.nlm.nih.gov

Effect of ATorvastatin On Chronic subdural Hematoma (ATOCH): a study protocol for a randomized controlled trial. [2018]