Oral Propanolol for Surgically Inaccessible Cavernous Malformations

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the role of propranolol as an alternative treatment for cavernous malformation in patients that may not be ideal candidates for surgery.

Detailed Description
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Patients between the ages of 1 and 80 years of age, that have been diagnosed with a spinal or cerebral cavernous malformation(s) that can not be surgically treated, will be enrolled in this randomized study. All eligible patients will be enrolled in one of two groups. Group 1 will receive oral propranolol tablets 3 times a day for 36 months. Group 2 will receive oral placebo tablets 3 times per day for 36 months. Prior to beginning treatment, all imaging, including MRIs, will be evaluated. During the first visit a blood sample will be collected for genomic analysis. Patients will return to clinic every 6 months. Each time the patient returns to clinic monitoring of how the patient is feeling and evaluation of how the patient is tolerating the propranolol will take place. At the end of the three years, evaluators will determine if the propranolol was able to stop the growth of the cavernous malformation and change the imaging features of the lesion on MRI. Once the study is completed patients will no longer receive the study drug.

Official Title
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Oral Propanolol for Surgically Inaccessible Cerebral and Spinal Cavernous Malformations

Conditions
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Cavernous Malformations,Cerebral and/or Spinal

Intervention / Treatment
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* Drug: Propranolol Oral Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of isolated or familial cavernous malformation syndrome: symptomatic cavernous malformation not amenable to surgical resection. familial cavernous malformation with seizure, other neurological symptom or surgically inaccessible lesion. Written and informed consent obtained prior to study enrollment. Subject is able and willing to return for outpatient visits. Negative pregnancy test at time of enrollment for women and child-bearing potential. Exclusion Criteria: Age less than 1 year-old. Propranolol allergy or allergy to other b-blockers. Estimated life expectancy of less than 1 year. History of severe anemia, cardiac dysfunction, or diabetes. A psychiatric or substance abuse problem that may interfere with study compliance. Pregnant and lactating women.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Propranolol Group<br>Group 1: Propranolol - group of randomized patients will receive one propranolol pill tid for 36 months. | Drug: Propranolol Oral Tablet<br>* A randomized group of patients with cerebral or spinal cavernous malformations, will receive a Propranolol Oral tablets, tid, for 36 months.<br>|
| Placebo Comparator: Group 2: Placebo Group<br>Group 2: Placebo - group of randomized patients will receive one placebo pill tid for 36 months. | Drug: Placebo Oral Tablet<br>* A randomized group of patients with cerebral or spinal cavernous malformations, will receive a Placebo Oral Tablet, tid, for 36 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of symptomatic and silent hemorrhages on MRI | Using MRI imaging the size of the cavernous malformation will be measured. The primary outcome is the number of symptomatic and silent hemorrhages as assessed by review of a fine-cut, axial T2-weighted MRI obtained at each visit. | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of de novo lesion formation; changes in rate of breakthrough seizures or other neurological deficits | The secondary outcome is the rate of de novo lesion formation; changes in rate of breakthrough seizures or other neurological deficits; quality of life measured using the SF-36 at each visit, patient satisfaction with treatment; and the incidence of treatment failure. | 36 months |