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Verapamil as Therapy for Children and Young Adults With Dravet Syndrome

Information source: Gillette Children's Specialty Healthcare
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Dravet Syndrome

Intervention: Verapamil (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: Beverly S. Wical, M.D.

Official(s) and/or principal investigator(s):
Beverly S Wical, MD, Principal Investigator, Affiliation: Gillette Children's Specialty Healthcare


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.

Clinical Details

Official title: Verapamil as Adjunctive Seizure Therapy for Children and Young Adults With Dravet Syndrome

Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Seizure Frequency

Secondary outcome: Frequency of myoclonic/absence/atypical absence seizures

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.


Minimum age: 2 Years. Maximum age: 25 Years. Gender(s): Both.


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

Locations and Contacts

Children's Memorial Hospital, Chicago, Illinois 60614, United States

Mayo Clinic, Rochester, Minnesota 55905, United States

Gillette Children's Specialty Healthcare, St. Paul, Minnesota 55101, United States

Mary Hitchcock Memorial Hospital, Lebanon, New Hampshire 03756, United States

Additional Information

Related publications:

Skluzacek JV, Watts KP, Parsy O, Wical B, Camfield P. Dravet syndrome and parent associations: the IDEA League experience with comorbid conditions, mortality, management, adaptation, and grief. Epilepsia. 2011 Apr;52 Suppl 2:95-101. doi: 10.1111/j.1528-1167.2011.03012.x.

Delogu AB, Spinelli A, Battaglia D, Dravet C, De Nisco A, Saracino A, Romagnoli C, Lanza GA, Crea F. Electrical and autonomic cardiac function in patients with Dravet syndrome. Epilepsia. 2011 Apr;52 Suppl 2:55-8. doi: 10.1111/j.1528-1167.2011.03003.x.

Iannetti P, Parisi P, Spalice A, Ruggieri M, Zara F. Addition of verapamil in the treatment of severe myoclonic epilepsy in infancy. Epilepsy Res. 2009 Jul;85(1):89-95. doi: 10.1016/j.eplepsyres.2009.02.014. Epub 2009 Mar 20.

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Last updated: March 24, 2015

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