Oral Propanolol for Surgically Inaccessible Cavernous Malformations

Oral Propanolol for Surgically Inaccessible Cerebral and Spinal Cavernous Malformations

The purpose of this study is to evaluate the role of propranolol as an alternative treatment for cavernous malformation in patients that may not be ideal candidates for surgery.

Study Overview

• Status: Unknown
• Conditions: Cavernous Malformations,Cerebral and/or Spinal
• Intervention / Treatment: Drug: Propranolol Oral Tablet; Drug: Placebo Oral Tablet

Detailed Description

Patients between the ages of 1 and 80 years of age, that have been diagnosed with a spinal or cerebral cavernous malformation(s) that can not be surgically treated, will be enrolled in this randomized study. All eligible patients will be enrolled in one of two groups. Group 1 will receive oral propranolol tablets 3 times a day for 36 months. Group 2 will receive oral placebo tablets 3 times per day for 36 months. Prior to beginning treatment, all imaging, including MRIs, will be evaluated. During the first visit a blood sample will be collected for genomic analysis. Patients will return to clinic every 6 months. Each time the patient returns to clinic monitoring of how the patient is feeling and evaluation of how the patient is tolerating the propranolol will take place. At the end of the three years, evaluators will determine if the propranolol was able to stop the growth of the cavernous malformation and change the imaging features of the lesion on MRI. Once the study is completed patients will no longer receive the study drug.

• Study Type: Interventional
• Enrollment (Anticipated): 346
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Univeristy of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 78 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of isolated or familial cavernous malformation syndrome:

   • symptomatic cavernous malformation not amenable to surgical resection.
   • familial cavernous malformation with seizure, other neurological symptom or surgically inaccessible lesion.
2. Written and informed consent obtained prior to study enrollment.
3. Subject is able and willing to return for outpatient visits.
4. Negative pregnancy test at time of enrollment for women and child-bearing potential.

Exclusion Criteria:

1. Age less than 1 year-old.
2. Propranolol allergy or allergy to other b-blockers.
3. Estimated life expectancy of less than 1 year.
4. History of severe anemia, cardiac dysfunction, or diabetes.
5. A psychiatric or substance abuse problem that may interfere with study compliance.
6. Pregnant and lactating women.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Propranolol Group; Group 1: Propranolol - group of randomized patients will receive one propranolol pill tid for 36 months.	Drug: Propranolol Oral Tablet; A randomized group of patients with cerebral or spinal cavernous malformations, will receive a Propranolol Oral tablets, tid, for 36 months.
Placebo Comparator: Group 2: Placebo Group; Group 2: Placebo - group of randomized patients will receive one placebo pill tid for 36 months.	Drug: Placebo Oral Tablet; A randomized group of patients with cerebral or spinal cavernous malformations, will receive a Placebo Oral Tablet, tid, for 36 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of symptomatic and silent hemorrhages on MRI	Using MRI imaging the size of the cavernous malformation will be measured. The primary outcome is the number of symptomatic and silent hemorrhages as assessed by review of a fine-cut, axial T2-weighted MRI obtained at each visit.	36 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of de novo lesion formation; changes in rate of breakthrough seizures or other neurological deficits	The secondary outcome is the rate of de novo lesion formation; changes in rate of breakthrough seizures or other neurological deficits; quality of life measured using the SF-36 at each visit, patient satisfaction with treatment; and the incidence of treatment failure.	36 months

Collaborators and Investigators

• Sponsor: University of Virginia
• Investigators: Principal Investigator: Yashar Kalani, MD, PHD, University of Virginia Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2018
• Primary Completion (Anticipated): January 1, 2019
• Study Completion (Anticipated): January 1, 2019

Study Registration Dates

• First Submitted: April 13, 2018
• First Submitted That Met QC Criteria: May 1, 2018
• First Posted (Actual): May 14, 2018

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 1, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular 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; 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: 20195

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes