Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation

Phase 2

Terminated

• Conditions: Cerebral Cavernous Malformations
• Interventions: Drug: Propranolol; Genetic: DNA and RNA Analysis

• Registration Number: NCT03474614
• Lead Sponsor: St. Joseph's Hospital and Medical Center, Phoenix

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.

Study Timeline

• Study Start: 2018-01-24
• Study First Submitted: 2018-03-05
• Study First Submitted QC: 2018-03-15
• Study First Posted: 2018-03-22
• Primary Completion: 2021-02-11
• Study Completion: 2021-02-11
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-17
• Last Update Posted: 2024-04-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
treatment group	DNA and RNA Analysis	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	DNA and RNA Analysis	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.
treatment group	Propranolol	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.

Primary Outcome Measures

Name	Time	Method
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	-7 to -10 days until surgery	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Barrow Neurological Institute; 🇺🇸 Phoenix, Arizona, United States