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Effect of Oral Propranolol on mRNA Expresssion in Symptomatic Cavernous Malformation

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ClinicalTrials.gov Identifier: NCT03474614
Recruitment Status : Recruiting
First Posted : March 22, 2018
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Norissa Honea, 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.


Condition or disease Intervention/treatment Phase
Cerebral Cavernous Malformations Drug: Propranolol Genetic: DNA and RNA Analysis Phase 2

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  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Two groups, intervention and control
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Effect of Oral Propranolol on mRNA Expression in Symptomatice Caavernous Malformation
Actual Study Start Date : January 24, 2018
Estimated Primary Completion Date : January 24, 2020
Estimated Study Completion Date : August 30, 2020


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

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




Primary Outcome Measures :
  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 [ Time Frame: -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 :
  1. To correlate treatment response to propranolol with the underlying established mutations in cerebral cavernous malformation (CCM) genes. [ Time Frame: -7 to -10 days until surgery ]
    correlate and compare genetic mutations seen in CCM genes in tissue of patients who receive propranolol preoperatively

  2. Record adverse event (tolerance to) related to low-dose oral propranolol (60mg ER once daily) [ Time Frame: -7 to -10 days until surgery ]
    Number of reported adverse events in patients taking propranolol



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03474614


Contacts
Contact: Dignity Health project leader 602-406-6267 Norissa.Honea@dignityhealth.org
Contact: Steev Mallon, BSN, RN 602-406-4217 Steev.Mallon@dignityhealth.org

Locations
United States, Arizona
Barrow Neurological Institute Recruiting
Phoenix, Arizona, United States, 85013
Contact: Norissa Honea, PhD, RN    602-406-6267    Norissa.Honea@dignityhealth.org   
Contact: Steev Mallon, BSN, RN    602-406-4217    Steev.Mallon@dignityhealth.org   
Principal Investigator: Joseph M Zabramski, MD         
Sponsors and Collaborators
St. Joseph's Hospital and Medical Center, Phoenix

Responsible Party: Norissa Honea, Research Program Manager, St. Joseph's Hospital and Medical Center, Phoenix
ClinicalTrials.gov Identifier: NCT03474614     History of Changes
Other Study ID Numbers: 17-0173-30-12
First Posted: March 22, 2018    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Congenital Abnormalities
Hemangioma, Cavernous, Central Nervous System
Hemangioma, Cavernous
Central Nervous System Vascular Malformations
Nervous System Malformations
Vascular Malformations
Cardiovascular Abnormalities
Propranolol
Hemangioma
Neoplasms, Vascular Tissue
Neoplasms by Histologic Type
Neoplasms
Nervous System Diseases
Cardiovascular Diseases
Hemostatic Disorders
Vascular Diseases
Hemorrhagic Disorders
Hematologic Diseases
Adrenergic beta-Antagonists
Adrenergic Antagonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Antihypertensive Agents
Vasodilator Agents