Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation

NCT03474614 | Terminated Phase 2 FDA Drug

• 1 other identifier: 17-0173-30-12
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Cerebral Cavernous Malformations

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• To correlate treatment response to propranolol with the underlying established mutations in cerebral cavernous malformation (CCM) genes.

  -7 to -10 days until surgery

• Record adverse event (tolerance to) related to low-dose oral propranolol (60mg ER once daily)

  -7 to -10 days until surgery

Study Arms (2)

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.

Drug: Propranolol; Genetic: DNA and RNA Analysis

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.

Genetic: DNA and RNA Analysis

Interventions

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)

treatment group

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

Control Group; treatment group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead

Study Sites (1)

Barrow Neurological Institute

Phoenix, Arizona, 85013, United States

Location

MeSH Terms

Conditions

Hemangioma, Cavernous, Central Nervous System

Interventions

Propranolol; DNA

Condition Hierarchy (Ancestors)

Hemangioma, Cavernous; Hemangioma; Neoplasms, Vascular Tissue; Neoplasms by Histologic Type; Neoplasms; Cavernous Sinus Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Central Nervous System Vascular Malformations; Nervous System Malformations; Vascular Malformations; Cardiovascular Abnormalities; Cardiovascular Diseases; Hemostatic Disorders; Vascular Diseases; Hemorrhagic Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Nucleic Acids; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Joseph Zabramski, MD

  Barrow Brain and Spine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Operations Manager

Model Details: Two groups, intervention and control

Study Record Dates

• First Submitted: March 5, 2018
• First Posted: March 22, 2018
• Study Start: January 24, 2018
• Primary Completion: February 11, 2021
• Study Completion: February 11, 2021
• Last Updated: April 19, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)