Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation

Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation

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 Overview

• Status: Terminated
• Conditions: Cerebral Cavernous Malformations
• Intervention / Treatment: Drug: Propranolol; Genetic: DNA and RNA Analysis

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 Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Barrow Neurological Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: treatment group; 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; 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); Genetic: DNA and RNA Analysis; 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
Other: Control Group; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Investigators: Principal Investigator: Joseph Zabramski, MD, Barrow Brain and Spine

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2018
• Primary Completion (Actual): February 11, 2021
• Study Completion (Actual): February 11, 2021

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 15, 2018
• First Posted (Actual): March 22, 2018

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Cardiovascular Abnormalities; Hemangioma; Neoplasms, Vascular Tissue; Nervous System Malformations; Vascular Malformations; Central Nervous System Vascular Malformations; Hemangioma, Cavernous; Cavernous Sinus Syndromes; Congenital Abnormalities; Hemangioma, Cavernous, Central Nervous System; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: 17-0173-30-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No