Treatment Resistant Epilepsy and N-Acetyl Cysteine

Study Overview
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Brief Summary
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This is a study to find out whether the dietary amino acid supplement, N-acetyl cysteine (NAC) is helpful in reducing the frequency of seizures in children with autism and comorbid epilepsy whose seizures are not responding well to usual medical treatment. The study is also looking to see if this supplement is helpful for immediate and ongoing treatment of symptoms of irritability. Additionally, this study will also look to see if certain substances in the blood that measure a specific type of stress on cells in the body can help tell us how NAC may be helping.

Detailed Description
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One third of patients with idiopathic autism have treatment resistant epilepsy, associated with earlier onset of seizures. In addition to insufficient response to medical treatment, they also have poorer responses to surgical and VNS approaches (Sansa et al 2011). Novel approaches to reduce seizure burden and improve quality of life for the children and their caregivers are needed. There is a plethora of basic research documenting elevated oxidative stress in animal models of seizures. Several animal models have decreased oxidative stress through using compounds with antioxidant effects, but suprisingly, few human studies have been done to date. This small open-label pilot study will examine the use of N-acetyl cysteine, an inexpensive but readily available over-the-counter nutritional supplement, to reduce seizure frequency in 10 youth with autism who have not responded completely to conventional anticonvulsant therapy

Official Title
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Pilot Study of N-acetyl Cysteine for Refractory Generalized Epilepsy in Children With Autism

Conditions
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Autistic Disorder, Seizures, Irritability

Intervention / Treatment
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* Drug: N-Acetyl Cysteine (NAC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children and adolescents/young adults ages 6-21, male or female, all races and ethnicities. Autism IQ less than 80 10 subjects with treatment resistant generalized epilepsy as defined by trials of 3 or more anticonvulsants with continued seizure frequency of at least 1 per week, need to use a helmet, or vagal nerve stimulator placement. Children with at least 1 grand mal/generalized seizure per week. Exclusion Criteria: Inability to swallow capsules In females, pregnancy or sexual activity Daily acetaminophen, glucocorticoid, or nonsteroidal anti-inflammatory drugs, or daily NAC or high-dose antioxidant vitamin supplements within 30 days of baseline. History of acute or chronic liver, renal, endocrine, infectious, autoimmune, hematologic, metabolic, or other disorder in the judgement of the study physician.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: N-Acetyl Cysteine (NAC)<br>NAC will be started at 500 mg by mouth twice daily for the first 2 weeks, then increased to 500 mg in the am and 1000 mg in the pm for week 3, and then increased to 1000 mg am and pm for weeks 4 through 8. Subjects will be maintained at the highest tolerated dose. | Drug: N-Acetyl Cysteine (NAC)<br>* NAC will be started at 500 mg by mouth twice daily for the first 2 weeks, then increased to 500 mg in the am and 1000 mg in the pm for week 3, and then increased to 1000 mg am and pm for weeks 4 through 8. Subjects will be maintained at the highest tolerated dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recruitment rate | screening to enrollment and retention rates will be measured | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seizure frequency | seizure count | up to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetyl cysteine, Refractory Seizures