What is the mechanism of action of this treatment?

The most common treatments for Neurofibromatosis (NF) often target oxidative stress and abnormal cellular signaling pathways. N-Acetyl Cysteine (NAC), an antioxidant and glutamate modulator, reduces oxidative stress and improves cellular function by scavenging reactive oxygen species (ROS) and regulating glutamate levels. This is particularly important for NF patients, as oxidative stress and glutamate dysregulation contribute to cognitive, behavioral, and motor impairments. By mitigating these factors, NAC and similar treatments can potentially improve quality of life and reduce the severity of symptoms in NF patients.

What side effects are associated with this type of intervention?

N-Acetyl Cysteine (NAC) is being studied for its potential to reduce cognitive, behavioral, and motor impairments in children with Neurofibromatosis Type 1 (NF1). Known side effects of NAC include gastrointestinal issues such as nausea, vomiting, and diarrhea, as well as potential allergic reactions like rash or itching. Other antioxidant treatments may have similar side effects, including gastrointestinal discomfort and allergic reactions. It is important to consult with a healthcare provider to understand the full range of potential side effects and benefits.

What prior FDA approvals exist?

Currently, there are no specific FDA-approved treatments for the cognitive, behavioral, and motor impairments associated with Neurofibromatosis Type 1 (NF1). However, N-Acetyl Cysteine (NAC), an antioxidant and glutamate modulating compound, is being studied for its potential benefits in reducing these impairments. Preliminary data from rodent models and uncontrolled clinical observations suggest that NAC may help correct cellular and behavioral abnormalities in NF1. While NAC shows promise, it is not yet FDA-approved for this specific use, and further research is needed to confirm its efficacy and safety.

What other types of research exist?

Promising novel alternatives to N-Acetyl Cysteine (NAC) for Neurofibromatosis patients include: 1) Sulforaphane, which has shown potential in modulating oxidative stress and improving behavioral outcomes in autism spectrum disorder, a condition with overlapping neurological features. 2) Ultra-high-dose methylcobalamin (vitamin B12), which has demonstrated neuroprotective effects in amyotrophic lateral sclerosis and could offer similar benefits in NF. 3) Transcranial Magnetic Stimulation (TMS), which has been explored for motor and cognitive improvements in various neurological disorders and may provide therapeutic benefits for NF patients.

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Antioxidant

Antioxidant Therapy with N-acetylcysteine for Neurofibromatosis Type 1 (NF1NAC Trial)

Phase 2

Waitlist Available

Led By Carlos E Prada, MD

Research Sponsored by Children's Hospital Medical Center, Cincinnati

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up at baseline and end of 8 weeks treatment with either nac or placebo (weeks 0 and 8 for treatment phase one of this cross-over double blind study and at weeks 10 and 18 for treatment phase two).

Summary

This trial tests N-Acetyl Cysteine (NAC), a common supplement, to see if it can help children with neurofibromatosis type 1 (NF1) who have cognitive, behavioral, and motor issues. NAC works by reducing harmful substances in the brain, potentially improving behavior and motor skills. NAC is a precursor to glutathione (GSH) and has been studied for its neuroprotective and cognitive benefits in various conditions.

Who is the study for?

This trial is for children aged 8-16 with Neurofibromatosis type 1 (NF1) and an IQ of 70 or above. They must not be on chemotherapy, have active brain lesions, epilepsy, or use certain medications like antidepressants. Children with asthma or at high risk for GI bleeding are excluded.

What is being tested?

The study tests if the antioxidant N-acetylcysteine (NAC) can improve learning and motor behavior in kids with NF1 compared to a placebo. It's a double-blind study, meaning neither participants nor researchers know who gets NAC or placebo.

What are the potential side effects?

While generally considered safe as it's available over-the-counter, NAC may cause infrequent bronchospasm in people with asthma and has potential risks when used as a mucolytic agent.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ at baseline and end of 8 weeks treatment with either nac or placebo (weeks 0 and 8 for treatment phase one of this cross-over double blind study and at weeks 10 and 18 for treatment phase two).

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~at baseline and end of 8 weeks treatment with either nac or placebo (weeks 0 and 8 for treatment phase one of this cross-over double blind study and at weeks 10 and 18 for treatment phase two).

This trial's timeline: 3 weeks for screening, Varies for treatment, and at baseline and end of 8 weeks treatment with either nac or placebo (weeks 0 and 8 for treatment phase one of this cross-over double blind study and at weeks 10 and 18 for treatment phase two). for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change From Baseline in ADHD Symptoms as Reported Via Parent/Teacher Surveys

Change From Baseline in Motor Function Measured by Physical and Neurological Examination for Subtle Signs (PANESS)

Secondary study objectives

Tumor Markers

Transcranial Magnetic Stimulation (TMS) - Cortical Silent Period

Other study objectives

Evaluation of Change From Baseline in Metabolomics Profiles as a Possible Disease Biomarker Metabolic Testing Biomarkers - Samples in Storage for Follow up Study

Side effects data

From 2014 Phase 3 trial • 264 Patients • NCT00650091

17%

Cough

14%

Dyspnea

13%

Upper respiratory tract infection

13%

Nausea

12%

Idiopathic Pulmonary Fibrosis

10%

Fatigue

10%

Idiopathic pulmonary fibrosis

Diarrhoea

Bronchitis

Dizziness

Sinusitis

Nasopharyngitis

Pneumonia

Headache

Atrial Fibrillation

Constipation

Acute Myocardial infarction

Oedema peripheral

Arthralgia

Intersticial Lung Disease

pneumothorax

Vomiting

Adverse Drug Reaction

Epistaxis

Dyspnoea

Lung Squamous Cell Carcinoma

Death

prostatitis

Dehydration

Prostate Cancer

syncope

Drug Fever

Exacerbation of Idiopathic Pulmonary Fibrosis

Atelectasis

Respiratory Tract Infection

100%

80%

60%

40%

20%

Study treatment Arm

Initial Study: Pred/AZA/NAC

N-Acetylcysteine

Placebo

Initial Study: Placebo

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: N-AcetylcysteineExperimental Treatment1 Intervention

Participants will be dosed with 70 mg/kg/dose (max dose 900 mg) three times per day of N-Acetylcysteine (NAC) for eight (8) weeks. This is a double-blind study, neither study participant nor study team members will know whether the participant is given study drug or placebo until after all data is collected.

Group II: PlaceboPlacebo Group1 Intervention

Participants will be dosed three times per day with a placebo for eight (8) weeks. This is a double-blind study, neither study participant nor study team members will know whether the participant is given study drug or placebo until after all data is collected.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

N-acetylcysteine (NAC)

2020

Completed Phase 3

~870

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Neurofibromatosis (NF) often target oxidative stress and abnormal cellular signaling pathways. N-Acetyl Cysteine (NAC), an antioxidant and glutamate modulator, reduces oxidative stress and improves cellular function by scavenging reactive oxygen species (ROS) and regulating glutamate levels. This is particularly important for NF patients, as oxidative stress and glutamate dysregulation contribute to cognitive, behavioral, and motor impairments. By mitigating these factors, NAC and similar treatments can potentially improve quality of life and reduce the severity of symptoms in NF patients.

Pharmacological inhibition of serine synthesis enhances temozolomide efficacy by decreasing O6-methylguanine DNA methyltransferase (MGMT) expression and reactive oxygen species (ROS)-mediated DNA damage in glioblastoma.Disulfiram and copper combination therapy targets NPL4, cancer stem cells and extends survival in a medulloblastoma model.Cyst(e)ine in nutrition formulation promotes colon cancer growth and chemoresistance by activating mTORC1 and scavenging ROS.