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lack of accrual
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| treatment group | Experimental | 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. |
|
| Control Group | Other | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Propranolol | Drug | 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) |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Joseph Zabramski, MD | Barrow Brain and Spine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Barrow Neurological Institute | Phoenix | Arizona | 85013 | United States |
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| ID | Term |
|---|---|
| D020786 | Hemangioma, Cavernous, Central Nervous System |
| ID | Term |
|---|---|
| D006392 | Hemangioma, Cavernous |
| D006391 | Hemangioma |
| D009383 | Neoplasms, Vascular Tissue |
| D009370 | Neoplasms by Histologic Type |
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| ID | Term |
|---|---|
| D011433 | Propranolol |
| D004247 | DNA |
| ID | Term |
|---|---|
| D050198 | Phenoxypropanolamines |
| D011412 | Propanolamines |
| D000605 | Amino Alcohols |
| D000438 | Alcohols |
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Two groups, intervention and control
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| DNA and RNA Analysis | Genetic | 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 |
|
Number of reported adverse events in patients taking propranolol |
| -7 to -10 days until surgery |
| D009369 | Neoplasms |
| D000096826 | Cavernous Sinus Syndromes |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D020785 | Central Nervous System Vascular Malformations |
| D009421 | Nervous System Malformations |
| D054079 | Vascular Malformations |
| D018376 | Cardiovascular Abnormalities |
| D002318 | Cardiovascular Diseases |
| D020141 | Hemostatic Disorders |
| D014652 | Vascular Diseases |
| D006474 | Hemorrhagic Disorders |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D000013 | Congenital Abnormalities |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D009930 |
| Organic Chemicals |
| D020005 | Propanols |
| D000588 | Amines |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D011083 | Polycyclic Compounds |
| D009696 | Nucleic Acids |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |