Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation

Study Overview
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Brief Summary
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This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Patients will be randomized into two groups: A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications, and a Control group of 10 (n=10) patients will receive only their routine medications. Currently, the only active treatment alternative for symptomatic cerebral cavernous malformations is surgery. A control group is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group.

Detailed Description
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This is a single center, randomized, trial that will enroll twenty (n=20) patients with a diagnosis of symptomatic cavernous malformations who are planned candidates for surgical resection by one of the investigators, and who meet all of the inclusion and exclusion criteria. Patients will be randomized into two groups: A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications, and a Control group of 10 (n=10) patients will receive only their routine medications. Currently, the only active treatment alternative for symptomatic cerebral cavernous malformations is surgery. A control group is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group.

Official Title
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Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation

Conditions
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Cerebral Cavernous Malformations

Intervention / Treatment
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* Drug: Propranolol
* Genetic: DNA and RNA Analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is at least 18-years of age. Clinical and imaging diagnosis of a symptomatic Isolated cavernous malformation or Familial cavernous malformation MRI Imaging Grade Type I or Type II (see Table 1) Patient is considered a candidate for surgical resection of their cavernous malformation Written and informed consent obtained prior to the study enrollment. Negative pregnancy test at time of enrollment for women of child-bearing potential. Heart rate greater than 50 beats per minute Systolic blood pressure > 90 mmHg Exclusion Criteria: Subject is less than 18-years of age. History of allergy to propranolol or other beta blockers. Patient is already taking another beta blocker for cardiac indications. History of asthma presently requiring any active treatment (oral medications or inhalers). History of cardiac dysfunction (as defined by the New York Heart Association Functional Classification grade II, III or IV). Heart rate < 50 beats per minute Systolic blood pressure < 90 mmHg History of diabetes and currently on any anti-hyperglycemic medication. Pregnant and lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Two groups, intervention and control
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: treatment group<br>A Treatment group of ten (n=10) patients that will receive oral propranolol at a dose of 60mg per day (one 60mg ER capsule per day) for 7- to 10-days prior to surgery plus their usual medications. | Drug: Propranolol<br>* The medication will be administered so that patient receives a minimum of 7- days and maximum of 10-days of treatment with propranolol prior to planned surgical resection of CCM (routine care)<br>Genetic: DNA and RNA Analysis<br>* During the operative procedure, a small sample of the patient's blood will be obtained and small (1 to 2cc) tissue sample from the resected cavernous malformation will be collected. The blood and tissue samples will be labeled and stored for subsequent DNA and RNA analysis<br>|
| Other: Control Group<br>A control group of 10 (n=10) patients will receive only their routine medications (no propranolol) during the (-7 to -10 days) preoperative period. A control group (n=10) is required to allow for a semi-quantitative comparison with mRNA and miRNA levels in the treatment group. | Genetic: DNA and RNA Analysis<br>* During the operative procedure, a small sample of the patient's blood will be obtained and small (1 to 2cc) tissue sample from the resected cavernous malformation will be collected. The blood and tissue samples will be labeled and stored for subsequent DNA and RNA analysis<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To measure effects of low-dose oral propranolol on global messenger RNA (mRNA) and microRNA (miRNA) expression in the blood and tissue of patients with CCM | compare changes noted in mRNA and miRNA in blood and CCM tissue samples of patients who do and do not receive propranolol preoperatively for CCM | -7 to -10 days until surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To correlate treatment response to propranolol with the underlying established mutations in cerebral cavernous malformation (CCM) genes. | correlate and compare genetic mutations seen in CCM genes in tissue of patients who receive propranolol preoperatively | -7 to -10 days until surgery | 
| Record adverse event (tolerance to) related to low-dose oral propranolol (60mg ER once daily) | Number of reported adverse events in patients taking propranolol | -7 to -10 days until surgery |