Atorvastatin Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial

The University of Chicago

Status and phase: Completed; Phase 2; Phase 1

Conditions: Cerebral Cavernous Malformation

Treatments: Other: Placebo; Drug: Atorvastatin

Study type: Interventional

Funder types: Other

Identifiers

NCT02603328

IRB18-0445

Details and patient eligibility

About

This phase I/II randomized, placebo-controlled, double-blinded, single-site clinical trial is designed to investigate the effect of a prolonged course of atorvastatin versus placebo on CCM lesional iron deposition assessed by validated quantitative susceptibility mapping (QSM) MRI studies in patients who suffered a symptomatic bleed within the preceding one year.

Full description

This phase I/II randomized, placebo-controlled, double-blinded, single-site clinical trial is designed to investigate the effect of a prolonged course of atorvastatin versus placebo on CCM lesional iron deposition assessed by validated quantitative susceptibility mapping (QSM) MRI studies in patients who suffered a symptomatic bleed within the preceding one year. Subjects will also be assessed by lesional and brain vascular permeability MRI using dynamic contrast enhanced quantitative perfusion (DCEQP) and a number of clinical evaluation tools. Subjects shall be followed for 2 years from randomization, the period of highest likelihood of rebleed after a recent CCM hemorrhage. Subjects will undergo clinical and MRI evaluations at baseline, and at 12 and 24 months during the study period. Enrolled subjects and the treating team will be blinded to treatment group allocation.

Enrollment: 80 patients

Sex: All

Ages: 18 to 80 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Diagnosis of CCM of any genotype supported by relevant imaging studies.
2. Symptomatic CCM bleeding event within 1 year prior to enrollment.
3. Must be willing/able to travel to the study site for all study visits (baseline, 12 months, and 24 months) over the course of the study period.

Exclusion criteria

1. Pre-menopausal women who are breastfeeding, pregnant or likely to get pregnant during the study period.
2. Previous cranial irradiation or surgical/radiosurgical treatment of CCM lesion.
3. Failure to pass MRI safety screening (claustrophobia, metal implant . . . etc)
4. Known allergy or intolerance to gadolinium.
5. Severely impaired renal function (eGFR < 60ml/min), active renal disease or status post-kidney transplants.
6. Statin therapy, for any indication, for more than 7 continuous days or greater than 14 total days within 12 months preceding enrollment.
7. Indication to use statin medication for current approved indication, unrelated to CCM
8. Known allergy or intolerance to statins
9. Liver dysfunction or active liver disease (including chronic viral hepatitis) defined as baseline serum transaminases levels twice the upper range of normal.
10. Previous diagnosis of skeletal muscle disorders of any cause (myopathy), or baseline creatine kinase level five times the upper range of normal.
11. Currently treated with or likely to need treatment with one or more of prohibited medications listed in the protocol.
12. Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
13. Serious illness (requiring systemic treatment and/or hospitalization) until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 30 days prior to study entry.
14. Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated, including conditions resulting in or precipitating myopathy (e.g. HIV, uncontrolled hypothyroidism).
15. In the investigator's opinion, the patient is unstable, and would benefit from a specific intervention rather than treatment with atorvastatin.
16. Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
17. No documentation of valid healthcare insurance.
18. No medical record confirmation of primary care physician.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups, including a placebo group

Treatment

Active Comparator group

Description:

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

Treatment:

Drug: Atorvastatin

Placebo

Placebo Comparator group

Description:

Identically looking capsules containing no active ingredient

Treatment:

Other: Placebo