Treatment Resistant Epilepsy and N-Acetyl Cysteine (TRE-NAC)

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Seizures; Autistic Disorder; Irritability
• Intervention / Treatment: Drug: N-Acetyl Cysteine (NAC)

Detailed Description

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

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Columbus, Ohio, United States, 43205
      • Nationwide Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Children and adolescents/young adults ages 6-21, male or female, all races and ethnicities.
2. Autism
3. IQ less than 80
4. 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.
5. Children with at least 1 grand mal/generalized seizure per week.

Exclusion Criteria:

1. Inability to swallow capsules
2. In females, pregnancy or sexual activity
3. Daily acetaminophen, glucocorticoid, or nonsteroidal anti-inflammatory drugs, or daily NAC or high-dose antioxidant vitamin supplements within 30 days of baseline.
4. History of acute or chronic liver, renal, endocrine, infectious, autoimmune, hematologic, metabolic, or other disorder in the judgement of the study physician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: N-Acetyl Cysteine (NAC); 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); 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
side effect rating form for children and adolescents	parent and child will be queried about changes in physical and mental health between study visits using a standardized form.	at baseline, 4, and 8 weeks
Aberrant Behavior Checklist	58 item parent-completed questionnaire	baseline, 4, and 8 weeks
Autism Spectrum Rating Scale	parent report form on symptoms and behaviors in autism	baseline, 4, and 8 weeks
oxidative stress measures	blood is collected and analyzed for oxidative changes in lipids, proteins.	baseline, 4, and 8 weeks

Collaborators and Investigators

• Sponsor: Nationwide Children's Hospital
• Investigators: Principal Investigator: Barbara Gracious, MD, Nationwide Children's Hospital

Study record dates

Study Major Dates

• Study Start: April 1, 2013
• Primary Completion (Actual): January 1, 2015
• Study Completion (Actual): January 1, 2015

Study Registration Dates

• First Submitted: February 3, 2014
• First Submitted That Met QC Criteria: February 3, 2014
• First Posted (Estimate): February 4, 2014

Study Record Updates

• Last Update Posted (Estimate): October 9, 2015
• Last Update Submitted That Met QC Criteria: October 7, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: N-acetyl cysteine; Refractory Seizures
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder; Epilepsy; Seizures; Autistic Disorder; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: IRB12-00325