Each subject will be dosed with approximately 70 mg/kg/day of NAC for 8 weeks. To facilitate drug compounding, three tiers of drug dose will be administered based on body weight as described in Table 3.
Table 3: NAC Dosing Participant's weight (kg) Dose (BID) < 20 700 mg 21-39 1050 mg > 40 1350 mg
*Max dose not to exceed 2700mg/day (1350mg BID)

Each subject will be dosed with placebo for 8 weeks.

Neurofibromatosis 1

Eight (8) weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC).

N-Acetyl cysteine

Eight (8) weeks of treatment with placebo.

Placebo

Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1

Antioxidant Therapy With N-acetylcysteine for Motor Behavior and/or Learning in Children With Neurofibromatosis Type 1

Characterize effects of NAC treatment on motor function in kids with NF1 using the Physical and Neurological Examination for Subtle Signs (PANESS). This is a validated scale that consistently demonstrates significant impairments in children with ADHD, and which preliminary data suggest may demonstrate more extreme problems in children with NF1 than age-matched healthy controls (unpublished data from CCHMC). The investigators hypothesize that motor function scores rated with the PANESS scale will improve after treatment with NAC. The range of this scale is 0-119, higher scores correlate with symptom severity (worse outcome).

Characterize effects of NAC treatment on ADHD symptoms in children with NF1. The investigators hypothesize that ADHD attention and hyperactive/impulsive symptoms, rated with the DuPaul Diagnostic and Statistical Manual Diploma in Social Medicine (DSM-5) based clinical rating scales, will improve after treatment with NAC. The range of this scale is 0-56, higher scores correlate with symptom severity (worse outcome).

Describe the function and physiology of the motor system using Transcranial Magnetic Stimulation (TMS) as a possible disease biomarker of NF1. Preliminary measures in an NF1 population also show abnormalities similar to established findings in ADHD. The investigators hypothesize that children with NF1 will have significantly less motor cortex inhibition using TMS measurements, and these measures will improve ("normalize") upon NAC treatment. The investigators will compare to our internal age-matched healthy controls at Cincinnati Children's.

To quantify microstructural properties of brain tissue based on water diffusion, glutathione GSH concentrations, and gamma-aminobutyric acid (GABA) concentration using brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in children with NF1. This will allow for regional correlation between imaging, spectroscopy and neuropsychometric outcomes. We will also determine if these magnetic resonance based outcomes correlate with clinical effects of NAC treatment.

Children's Hospital Medical Center, Cincinnati

United States Department of Defense

This is a phase II, double blind, placebo-controlled clinical trial with the goal to explore safety, tolerability, and efficacy of N-acetylcysteine (NAC).

In order to preserve the double-masking of the trial, only the investigation pharmacy will be unmasked. Both treatments (NAC and placebo) will be distributed from the investigational pharmacy. Except for the pharmacist, all staff will be blinded to the treatment sequence.

neurofibromatoses/глутатион

Antioxidant Therapy With N-acetylcysteine for Children With Neurofibromatosis Type 1

Најкомплетнија база лековитог биља подржана науком