- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02603328
Atorvastatin Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC) Trial (AT CASH EPOC)
October 4, 2023 updated by: University of Chicago
Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cavernous Angiomas With Symptomatic Hemorrhage Exploratory Proof of Concept (AT CASH EPOC)
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.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Interventional
Enrollment (Actual)
80
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Illinois
-
Chicago, Illinois, United States, 60637
- University of Chicago
-
-
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.
Eligibility Criteria
Ages Eligible for Study
16 years to 78 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Inclusion Criteria:
- Diagnosis of CCM of any genotype supported by relevant imaging studies.
- Symptomatic CCM bleeding event within 1 year prior to enrollment.
- 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:
- Pre-menopausal women who are breastfeeding, pregnant or likely to get pregnant during the study period.
- Previous cranial irradiation or surgical/radiosurgical treatment of CCM lesion.
- Failure to pass MRI safety screening (claustrophobia, metal implant . . . etc)
- Known allergy or intolerance to gadolinium.
- Severely impaired renal function (eGFR < 60ml/min), active renal disease or status post-kidney transplants.
- Statin therapy, for any indication, for more than 7 continuous days or greater than 14 total days within 12 months preceding enrollment.
- Indication to use statin medication for current approved indication, unrelated to CCM
- Known allergy or intolerance to statins
- Liver dysfunction or active liver disease (including chronic viral hepatitis) defined as baseline serum transaminases levels twice the upper range of normal.
- Previous diagnosis of skeletal muscle disorders of any cause (myopathy), or baseline creatine kinase level five times the upper range of normal.
- Currently treated with or likely to need treatment with one or more of prohibited medications listed in the protocol.
- Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- 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.
- 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).
- In the investigator's opinion, the patient is unstable, and would benefit from a specific intervention rather than treatment with atorvastatin.
- Inability or unwillingness of subject or legal guardian/representative to give written informed consent.
- No documentation of valid healthcare insurance.
- No medical record confirmation of primary care physician.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: Treatment
Atorvastatin 80mg OD (optimal dose).
Treatment dose will be de-escalated to 40mg based on reported adverse events.
|
40-80 mg OD
|
Placebo Comparator: Placebo
Identically looking capsules containing no active ingredient
|
inactive
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
mean percent change in lesional QSM per year (called the change score)
Time Frame: End of study (24-month) MRI scan
|
Each patient contributes two outcome measurements (at year 1 and year 2) based on intention-to-treat.
Evaluation of the intervention on this outcome will be performed as a time-averaged difference between two arms using a repeated measures analysis implemented as an unadjusted linear mixed model.
Patients with outcome measurements in both periods will be included in the initial intention-to-treat analysis.
In cases with multiple lesions, only QSM measurements in the lesion with initial hemorrhage (index lesion) shall be considered for the primary outcome assessment.
|
End of study (24-month) MRI scan
|
Percent QSM change per year
Time Frame: End of study (24-month) MRI scan
|
A secondary analysis of the percent QSM change per year shall be conducted per treatment rendered for all patients with at least one annual epoch of measurements.
|
End of study (24-month) MRI scan
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in DCEQP vascular permeability measurements in the index lesion and in brain (white matter far from lesion)
Time Frame: End of study (24-month) MRI scan
|
Changes in DCEQP vascular permeability measurements in the index lesion and in brain (white matter far from lesion)
|
End of study (24-month) MRI scan
|
Rates of QSM and DCEQP biomarker events
Time Frame: End of study (24-month) MRI scan
|
Rates of QSM and DCEQP biomarker events, representing increases in index lesional QSM or DCEQP above previously articulated "biomarker thresholds"; rates of clinically overt hemorrhages in the index lesion per adjudicated criteria; and rates of lesional expansion, defined as an increase in maximum lesion diameter on T2 sequences by 2 or more mm
|
End of study (24-month) MRI scan
|
Adverse event rates
Time Frame: End of study (24-month) MRI scan
|
End of study (24-month) MRI scan
|
|
Serious adverse event rates
Time Frame: End of study (24-month) MRI scan
|
End of study (24-month) MRI scan
|
|
Drug compliance by tracking daily medication bottle opening
Time Frame: End of study (24-month) MRI scan
|
We plan to use a compliance device that would record every time the bottle was opened, thus allowing the study team to track compliance with the protocol and help keep subjects accountable.
|
End of study (24-month) MRI scan
|
Changes in functional outcome as measured using the modified Rankin scale which measures the degree of disability or dependence in patients with neurological disability.
Time Frame: End of study (24-month) MRI scan
|
Using the modified Rankin scale, we will track subjects' functional outcome changes over the course of the trial.
|
End of study (24-month) MRI scan
|
Impact of sex on primary and secondary outcomes (pre specified subgroup analyses)
Time Frame: End of study (24-month) MRI scan
|
End of study (24-month) MRI scan
|
|
Impact of genotype on primary and secondary outcomes (pre specified subgroup analyses)
Time Frame: End of study (24-month) MRI scan
|
End of study (24-month) MRI scan
|
|
Impact of lesion location on primary and secondary outcomes (pre specified subgroup analyses)
Time Frame: End of study (24-month) MRI scan
|
End of study (24-month) MRI scan
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Study Chair: Issam A Awad, MD, Director of Neurovascular Surgery University of Chicago Medicine and Biological Sciences
- Study Chair: Daniel F Hanley, MD, Director, Division of Brain Injury Outcomes Service The Johns Hopkins Medical Institutions
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 Major Dates
Study Start (Actual)
July 17, 2018
Primary Completion (Estimated)
December 31, 2024
Study Completion (Estimated)
June 30, 2025
Study Registration Dates
First Submitted
November 9, 2015
First Submitted That Met QC Criteria
November 9, 2015
First Posted (Estimated)
November 11, 2015
Study Record Updates
Last Update Posted (Actual)
October 6, 2023
Last Update Submitted That Met QC Criteria
October 4, 2023
Last Verified
October 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Nervous System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Cardiovascular Abnormalities
- Hemangioma
- Neoplasms, Vascular Tissue
- Nervous System Malformations
- Vascular Malformations
- Central Nervous System Vascular Malformations
- Hemorrhage
- Congenital Abnormalities
- Hemangioma, Cavernous, Central Nervous System
- Hemangioma, Cavernous
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antimetabolites
- Anticholesteremic Agents
- Hypolipidemic Agents
- Lipid Regulating Agents
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Atorvastatin
Other Study ID Numbers
- IRB18-0445
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cerebral Cavernous Malformation
-
University of California, San FranciscoUniversity of Chicago; National Institute of Neurological Disorders and Stroke... and other collaboratorsRecruitingCerebral Cavernous Malformations | Cavernous Angioma, Familial | Cerebral Cavernous HemangiomaUnited States
-
yuanli ZhaoPeking University International HospitalRecruitingEpilepsy | Seizures | Seizures, Epileptic | Cavernous Malformation, Cerebral | Cavernous Angioma | Cavernous Hemangioma | Cavernous Hemangioma of BrainChina
-
University of New MexicoNational Institute of Neurological Disorders and Stroke (NINDS); University...TerminatedCerebral Cavernous Malformations | Cavernous Angioma, Familial | Cerebral Cavernous HemangiomaUnited States
-
University of ChicagoJohns Hopkins University; Mayo Clinic; National Institute of Neurological Disorders... and other collaboratorsCompletedCerebral Cavernous Malformation | Cavernous Angioma | Cavernoma | CCM | Cerebral Cavernous Malformations 1 | Cerebral Cavernous Malformations 2 | Cerebral Cavernous Malformations 3United States
-
First Affiliated Hospital of Fujian Medical UniversityRecruitingCerebral Cavernous MalformationsChina
-
University of VirginiaUnknownCavernous Malformations,Cerebral and/or SpinalUnited States
-
St. Joseph's Hospital and Medical Center, PhoenixTerminatedCerebral Cavernous MalformationsUnited States
-
Recursion Pharmaceuticals Inc.Active, not recruitingCerebral Cavernous MalformationUnited States
-
University of New MexicoUniversity of California, San FranciscoRecruitingCerebral Cavernous MalformationUnited States
-
Mario Negri Institute for Pharmacological ResearchIFOM, The FIRC Institute of Molecular OncologyCompletedCerebral Cavernous MalformationItaly
Clinical Trials on Atorvastatin
-
GlaxoSmithKlineCompletedDiabetes Mellitus, Type 2Korea, Republic of, Malaysia, Philippines, Thailand, Russian Federation, Mexico
-
Organon and CoCompleted
-
Obafemi Awolowo University Teaching HospitalOpen PhilanthropyRecruitingTuberculosis | Pulmonary Tuberculosis | Koch's DiseaseNigeria
-
Hippocration General HospitalCompletedCoronary Artery Disease | Atherosclerosis | Endothelial Dysfunction | Oxidative Stress | HMG-CoA Reductase Inhibitor ToxicityGreece
-
PfizerCompletedHypertriglyceridemia | Hyperlipoproteinemia Type IVUnited States, Canada
-
St. Olavs HospitalUllevaal University Hospital; Oslo University Hospital; University Hospital of... and other collaboratorsNot yet recruiting
-
Organon and CoCompleted
-
Zhejiang Hisun Pharmaceutical Co. Ltd.Unknown
-
Beijing HospitalUnknownCarotid Artery StenosisChina