Clinical trial NCT03523650: Oral Propanolol for Surgically Inaccessible Cavernous Malformations
Official title: Oral Propanolol for Surgically Inaccessible Cerebral and Spinal Cavernous Malformations
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Cavernous Malformations,Cerebral and/or Spinal
Lead sponsor: University of Virginia
Sponsor class: OTHER
First posted: 2018-05-14
Enrollment: 346
Sex: ALL
Minimum age (years): 1
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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.
2. Written and informed consent obtained prior to study enrollment.
3. Subject is able and willing to return for outpatient visits.
4. Negative pregnancy test at time of enrollment for women and child-bearing potential.

Exclusion Criteria:

1. Age less than 1 year-old.
2. Propranolol allergy or allergy to other b-blockers.
3. Estimated life expectancy of less than 1 year.
4. History of severe anemia, cardiac dysfunction, or diabetes.
5. A psychiatric or substance abuse problem that may interfere with study compliance.
6. Pregnant and lactating women.

Primary outcomes:
measure: Number of symptomatic and silent hemorrhages on MRI
timeFrame: 36 months
Secondary outcomes:
measure: Rate of de novo lesion formation; changes in rate of breakthrough seizures or other neurological deficits
timeFrame: 36 months
Other outcomes:
Locations:
city: Charlottesville
country: United States
facility: Univeristy of Virginia
state: Virginia
Study officials:
affiliation: University of Virginia Medical Center
name: Yashar Kalani, MD, PHD
role: PRINCIPAL_INVESTIGATOR
References: