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Trial record 2 of 7 for:    cerebral cavernous malformations

Atorvastatin Therapy in Cerebral Cavernous Malformation: A Proof of Concept Phase I/II Trial (AT-CCM I/II)

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2016 by University of Chicago
Sponsor:
Collaborator:
Johns Hopkins University
Information provided by (Responsible Party):
University of Chicago
ClinicalTrials.gov Identifier:
NCT02603328
First received: November 9, 2015
Last updated: March 4, 2016
Last verified: March 2016
  Purpose
The study aims to demonstrate that extended course atorvastatin therapy reduces lesional iron deposition without increasing the risk of rebleeding (acute hemorrhage) in patients with cerebral cavernous malformation (CCM). Subjects will be randomized to daily atorvastatin (20,40 or 80mg PO) or placebo and followed for 36 months, or until a clinically overt CCM hemorrhage or attrition from drug related adverse events. Subjects will undergo a total of four MRI scans with biomarker studies, and serial clinical assessments.

Condition Intervention Phase
Cerebral Cavernous Malformation
Drug: Atorvastatin
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: Phase I-II Randomized, Placebo-Controlled, Single-Blinded, Single-Site Clinical Trial of Atorvastatin in the Treatment of Cerebral Cavernous Malformation

Resource links provided by NLM:


Further study details as provided by University of Chicago:

Primary Outcome Measures:
  • lesional iron concentration [ Time Frame: End of study (36-month) MRI scan ]
    Lesional iron load measured by QSM protocol during the end of trial visit.


Secondary Outcome Measures:
  • Rebleeding Rate [ Time Frame: Three years ]
    Number of recurrent hemorrhagic events on Atorvastatin Vs Placebo


Estimated Enrollment: 60
Study Start Date: July 2016
Estimated Study Completion Date: June 2021
Estimated Primary Completion Date: June 2021 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Treatment
Atorvastatin 40mg OD for the first six month into the trial. Treatment dose will then be escalated based on biomarker evaluation at the six month visit.
Drug: Atorvastatin
20-80 mg OD
Placebo Comparator: Placebo
Identically looking capsules containing no active ingredient
Other: Placebo

Detailed Description:
The proposed study is a prospective phase I/II randomized, placebo-controlled, single-blinded, single-site clinical trial. Sixty CCM subjects will be randomized in a 2:1 fashion to receive either atorvastatin (40 mg PO) or placebo, All subjects will undergo baseline and three interval MRI studies at 6, 18 and 36 months throughout the three-year study period. Systematic dose escalation regime will be followed based on lesional and brain vascular permeability assessed by dynamic contrast enhanced quantitative perfusion (DCEQP). At the six month MRI scan, subjects with > 30% reduction in either lesional or brain permeability will be continued on the same dose. If neither lesional or background brain permeability exhibit >30% reduction, the dose will be escalated to 80 mg in the absence of any side effects. Enrolled subjects and investigators assessing dose related DCEQP and iron deposition in lesions by Quantitative Susceptibility Mapping (QSM) will be blinded to treatment group allocation.
  Eligibility

Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of CCM of any genotype supported by relevant imaging studies.
  2. Symptomatic CCM bleeding event within 2 years prior to enrollment.
  3. Must be willing/able to travel to the study site for all study visits (baseline, 6 months, 18 months and 36 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.
  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, 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 section 5.3.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02603328

Contacts
Contact: Maged D Fam, MD 7732514624 mfam@surgery.bsd.uchicago.edu
Contact: Agnieska Stadnik, MS, CCRP Phone: (773) 702-8996 mailto:astadnik@surgery.bsd.uchicago.edu

Sponsors and Collaborators
University of Chicago
Johns Hopkins University
Investigators
Study Chair: Issam A Awad, MD, MSc, FACS, MA (hon) 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
  More Information

Responsible Party: University of Chicago
ClinicalTrials.gov Identifier: NCT02603328     History of Changes
Other Study ID Numbers: IRB16-0024
Study First Received: November 9, 2015
Last Updated: March 4, 2016

Keywords provided by University of Chicago:
Cerebral cavernous malformation
Statins
MRI
Permeability
Quantitative susceptibility mapping

Additional relevant MeSH terms:
Congenital Abnormalities
Hemangioma, Cavernous, Central Nervous System
Hemangioma, Cavernous
Central Nervous System Vascular Malformations
Nervous System Malformations
Vascular Malformations
Cardiovascular Abnormalities
Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Nervous System Diseases
Cardiovascular Diseases
Hemostatic Disorders
Vascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on March 24, 2017