Clinical trial NCT03474614: Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation
Official title: Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Cerebral Cavernous Malformations
Lead sponsor: St. Joseph's Hospital and Medical Center, Phoenix
Sponsor class: OTHER
First posted: 2018-03-22
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two groups, intervention and control
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Subject is at least 18-years of age.
2. Clinical and imaging diagnosis of a symptomatic Isolated cavernous malformation or Familial cavernous malformation
3. MRI Imaging Grade Type I or Type II (see Table 1)
4. Patient is considered a candidate for surgical resection of their cavernous malformation
5. Written and informed consent obtained prior to the study enrollment.
6. Negative pregnancy test at time of enrollment for women of child-bearing potential.
7. Heart rate greater than 50 beats per minute
8. Systolic blood pressure \> 90 mmHg

Exclusion Criteria:

1. Subject is less than 18-years of age.
2. History of allergy to propranolol or other beta blockers.
3. Patient is already taking another beta blocker for cardiac indications.
4. History of asthma presently requiring any active treatment (oral medications or inhalers).
5. History of cardiac dysfunction (as defined by the New York Heart Association Functional Classification grade II, III or IV).
6. Heart rate \< 50 beats per minute
7. Systolic blood pressure \< 90 mmHg
8. History of diabetes and currently on any anti-hyperglycemic medication.
9. Pregnant and lactating women.

Primary outcomes:
measure: 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
timeFrame: -7 to -10 days until surgery
Secondary outcomes:
measure: To correlate treatment response to propranolol with the underlying established mutations in cerebral cavernous malformation (CCM) genes.
timeFrame: -7 to -10 days until surgery
measure: Record adverse event (tolerance to) related to low-dose oral propranolol (60mg ER once daily)
timeFrame: -7 to -10 days until surgery
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
Study officials:
affiliation: Barrow Brain and Spine
name: Joseph Zabramski, MD
role: PRINCIPAL_INVESTIGATOR
References: