Trial record 4 of 14 for:    Dravet Syndrome

Verapamil as Therapy for Children and Young Adults With Dravet Syndrome

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by Gillette Children's Specialty Healthcare
Sponsor:
Collaborators:
Mayo Clinic
Ann & Robert H Lurie Children's Hospital of Chicago
Mary Hitchcock Memorial Hospital
Information provided by (Responsible Party):
Beverly S. Wical, M.D., Gillette Children's Specialty Healthcare
ClinicalTrials.gov Identifier:
NCT01607073
First received: May 24, 2012
Last updated: October 24, 2013
Last verified: October 2013
  Purpose

This study will assess how well the drug verapamil can improve control of seizures and dysautonomia symptoms in children and young adults diagnosed with Dravet syndrome. The safety of verapamil when given with all concomitant medications will also be assessed.


Condition Intervention Phase
Dravet Syndrome
Drug: Verapamil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Verapamil as Adjunctive Seizure Therapy for Children and Young Adults With Dravet Syndrome

Resource links provided by NLM:


Further study details as provided by Gillette Children's Specialty Healthcare:

Primary Outcome Measures:
  • Seizure Frequency [ Time Frame: Baseline, 8 weeks, 12 weeks, 16 weeks, 24 weeks, and 35 weeks ] [ Designated as safety issue: No ]
    The primary study endpoint is GTCS seizure frequency. A reduction in the number and severity of seizures is anticipated.


Secondary Outcome Measures:
  • Frequency of myoclonic/absence/atypical absence seizures [ Time Frame: Baseline, 8 weeks, 12 weeks, 16 weeks, 24 weeks, and 35 weeks ] [ Designated as safety issue: No ]
    We anticipate a reduction in myoclonic, absence, and atypical absence seizures as well.


Estimated Enrollment: 20
Study Start Date: April 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: Verapamil

    Verapamil will be prepared as a solution. A 50mg/ml oral suspension may be made with immediate release tablets and either a 1:1 mixture of Ora-Sweet and Ora-Plus or a 1:1 mixture of Ora-Sweet SF and Ora-Plus will be used.

    Children will start on a 4 weeks titration period:

    Week 1: 1mg/kg/day divided BID Week 2: 2mg/kg/day divided BID or TID Week 3: 3mg/kg/day divided BID or TID Week 4: 4mg/kg/day divided TID

    In event of adverse events, and in consultation with the family and treating physician, the dosage may be decreased to 2mg/kg/day and remain at that dose for the remainder of the study.

    Other Names:
    • Calan
    • Covera
    • Isoptin
    • Verelan
Detailed Description:

Dravet syndrome (DS) is a devastating form of pediatric seizure disorder (epilepsy), often related to abnormalities of one of the genes that controls sodium channel function in the brain (SCN1A). Most children with DS experience continued seizures even with optimal treatment of currently available anti-seizure therapies [1]. Many of these seizures are prolonged, and can be life threatening.

This pilot study will assess the efficacy of verapamil in improving control of seizures in children and young adults DS. This will be done by adding verapamil as open label adjunctive therapy to medications already being given. Investigators will assess the effect of verapamil therapy on seizure control and on signs of autonomic dysfunction observable to the parents/guardians. Signs of autonomic function include body temperature regulation, sweating, heart rate, pupil size, and flushing of the skin. Iannetti, et al reported treating 2 children with clinical DS (one with an SCN1A mutation) with verapamil as adjunctive therapy [2]. Both children had a positive clinical response persisting for a number of months. No adverse effects were noted. We have treated an additional 4 children with DS with verapamil. There have been no significant adverse effects; 3 of 4 have experienced improved seizure control for months also.

Verapamil has been shown to affect autonomic tone in patients with cardiac disorders (eg. high blood pressure, heart attack). It alters the balance between parts of the autonomic nervous system's function (called sympathetic and parasympathetic function) with a shift toward decreased sympathetic tone and increased parasympathetic (vagus nerve) tone [8, 9, 10]. Verapamil is used as an effective agent to treat certain types of autonomic headaches in both adults and children. In cluster headaches, autonomic symptoms (tearing, nasal congestion, facial sweating, papillary constriction) are prominent; verapamil is an accepted treatment [11, 12].

Intense emotion triggers seizures in a subset of children with DS. Modulation of autonomic function is likely an integral part of seizure threshold in those so affected. Children with DS have a higher rate of signs of abnormal autonomic function than do controls [13]. Cardiac autonomic control is also altered in these children, with a shift in the balance between sympathetic (relatively overactive) and parasympathetic (relatively less active) tone [14]. Similar findings have been identified in adults with intractable epilepsy and children with partial epilepsy [15, 16, 17]. Verapamil's action in stabilizing the balance of sympathetic and parasympathetic tone may play a role altering autonomic tone abnormalities in children with DS as well. This may be a part of the mechanism that leads to improved seizure control.

Verapamil has been in clinical use for ~ 25 years. The FDA has granted an Investigational New Drug approval for use of this medication in this population of children and young adults. Investigators propose to add it to the patient's existing medications, and evaluate potential improvement in seizure control. Potential side effects will be screened. Investigators will monitor liver function with blood tests as well as concentrations of anti-seizure medications. Verapamil and nor-verapamil levels will be assessed twice also. Testing of heart rhythm (EKG) will be done before the study starts and twice more during the study.

  Eligibility

Ages Eligible for Study:   2 Years to 25 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 2 to 25 years old
  • Onset of seizures in first year of life
  • seizure type usually generalized tonic-clonic, clonic, or hemiclonic, often prolonged (>10 minutes)
  • myoclonic jerks/myoclonic seizures
  • history of normal development at seizure onset with subsequent developmental delay or regression which occurs after seizure onset
  • presence of documented abnormality on the SCN1A gene
  • medically intractable epilepsy: must have been on at least 2 prior antiepileptic medications without adequate control of epilepsy
  • subject is capable of giving informed consent (or assent if possible) or has an acceptable surrogate capable of giving informed consent on the subject's behalf

Exclusion Criteria:

  • use of clonidine, propranolol, carbamazepine, oxcarbazine, stiripentol, lamotrigine, or cyclosporine
  • Abnormalities of cardiac conduction or rhythm (excluding sinus arrhythmia) on screening EKG
  • significant use of grapefruit juice
  • ketogenic diet
  • pregnancy
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01607073

Contacts
Contact: Heather Wendorf, MPH, CCRC 651-325-2314 hwendorf@gillettechildrens.com
Contact: Beverly S Wical, MD 651-325-2325 BWical@gillettechildrens.com

Locations
United States, Illinois
Children's Memorial Hospital Not yet recruiting
Chicago, Illinois, United States, 60614
Contact: Linda Laux, MD    773-883-9159      
Principal Investigator: Linda Laux, MD         
United States, Minnesota
Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Elaine Wirrell, MD    507-284-2511      
Principal Investigator: Elaine Wirrell, MD         
Gillette Children's Specialty Healthcare Recruiting
St. Paul, Minnesota, United States, 55101
Contact: Heather Wendorf, MPH, CCRC    651-325-2314    hwendorf@gillettechildrens.com   
Contact: Beverly Wical, M.D.    651-325-2325    BWical@gillettechildrens.com   
Principal Investigator: Beverly S Wical, M.D.         
Sub-Investigator: Timothy Feyma, MD         
United States, New Hampshire
Mary Hitchcock Memorial Hospital Not yet recruiting
Lebanon, New Hampshire, United States, 03756
Contact: Julie A Bursey    603-653-9948    Julie.A.Bursey@hitchcock.org   
Contact: Richard P Morse, MD       Richard.P.Morse@hitchcock.org   
Principal Investigator: Richard P Morse, MD         
Sponsors and Collaborators
Beverly S. Wical, M.D.
Mayo Clinic
Ann & Robert H Lurie Children's Hospital of Chicago
Mary Hitchcock Memorial Hospital
Investigators
Principal Investigator: Beverly S Wical, MD Gillette Children's Specialty Healthcare
  More Information

Publications:

Responsible Party: Beverly S. Wical, M.D., Pediatric Neurologist, Gillette Children's Specialty Healthcare
ClinicalTrials.gov Identifier: NCT01607073     History of Changes
Other Study ID Numbers: IND 113666
Study First Received: May 24, 2012
Last Updated: October 24, 2013
Health Authority: United States: Food and Drug Administration
United States: University of Minnesota Institutional Review Board

Keywords provided by Gillette Children's Specialty Healthcare:
Dravet
seizures
verapamil

Additional relevant MeSH terms:
Syndrome
Epilepsies, Myoclonic
Disease
Pathologic Processes
Epilepsy
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Verapamil
Anti-Arrhythmia Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Calcium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Vasodilator Agents

ClinicalTrials.gov processed this record on October 01, 2014