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Antioxidant

Antioxidant Therapy for Neurofibromatosis Type 1 (DoDNAC Trial)

Phase 2
Recruiting
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
Has a diagnosis of NF1 (neurofibromatosis type 1)
Has an IQ (intelligence quotient) at or above 70
Must not have
Have epilepsy
Active intracranial lesions (abnormality found on brain imaging such as an MRI) (stable low-grade glioma is acceptable) or epilepsy diagnosis
Timeline
Screening 3 weeks
Treatment Varies
Follow Up through 12 weeks (at weeks 0, 8, and 12)
Awards & highlights

Summary

This trial is testing a medication called NAC in children aged 8-16 with a condition called NF1. These children often have problems with movement and behavior, and there is no current treatment for these issues. NAC works by reducing harmful molecules in the brain, which may help improve these symptoms.

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 have a specific abnormal score on a motor skills test and be on stable doses of any psychotropic medication. It excludes those without NF1, under chemotherapy, with epilepsy, certain medical devices, using specific drugs like MEKINIST within the last month, or with severe psychiatric disorders.
What is being tested?
The study tests N-acetylcysteine (NAC), an antioxidant therapy against a placebo in children with NF1 to see if it improves cognitive and motor functions. This Phase II trial is double-blind and controlled; participants won't know which treatment they're getting to ensure unbiased results.
What are the potential side effects?
While closely monitoring for side effects during the trial, potential risks may include allergic reactions due to NAC's mucolytic properties causing bronchospasm (tightening of airways), gastrointestinal bleeding in high-risk individuals, and other unspecified drug-related adverse events.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below
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I have been diagnosed with neurofibromatosis type 1.
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My IQ is 70 or higher.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:
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I have epilepsy.
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I have a stable low-grade brain tumor or epilepsy.
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I do not have Neurofibromatosis type 1.
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I am at high risk for serious stomach or intestine bleeding.
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I am currently taking medication for depression, mood, or dopamine regulation.
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I am currently on chemotherapy or had it within the last 6 months.
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My IQ is below 70.
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I am either younger than 8 or older than 16 years old.

Timeline

Screening ~ 3 weeks
Treatment ~ Varies
Follow Up ~through 12 weeks (at weeks 0, 8, and 12)
This trial's timeline: 3 weeks for screening, Varies for treatment, and through 12 weeks (at weeks 0, 8, and 12) 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 Motor Function Measured by Physical and Neurological Examination for Subtle Signs (PANESS)
Secondary study objectives
Change from Baseline in ADHD Symptoms as Reported via Parent/Teacher Surveys
Change from Baseline in Microstructural Properties of Brain Tissue Visualized by Magnetic Resonance Imaging (MRI)
Change from Baseline in Motor Function and Physiology Measured by Transcranial Magnetic Stimulation (TMS)

Side effects data

From 2024 Phase 2 trial • 13 Patients • NCT03499249
62%
GGT 400 IU/L >pre-KP value
46%
AST 400 IU/L >pre-KP value
31%
Loss of an IV
23%
Emesis with feeds
15%
Febrile illness
15%
Conjugated bilirubin 3 mg/dL >pre-KP value
8%
Tachycardia
8%
ALT 700 IU/L >pre-KP value
8%
INR >2.0
8%
Total bilirubin 5 mg/dL >pre-KP value
100%
80%
60%
40%
20%
0%
Study treatment Arm
N-Acetylcysteine Treatment

Trial Design

3Treatment groups
Experimental Treatment
Active Control
Placebo Group
Group I: N-Acetylcysteine (NAC)Experimental Treatment1 Intervention
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)
Group II: Single Visit/Non-Treatment ArmActive Control1 Intervention
Based on preliminary data, an additional "Single visit, non-treatment" cohort will include 40 individuals with NF1 for a single "biomarker" study visit. These individuals will undergo motor function (PANESS) and brain-based measures (TMS, MRI-MRS, DTI) as biomarkers of impaired executive function (ADHD-RS; BRIEF-2; TOVA) but will not be assigned to receive NAC/Placebo.
Group III: PlaceboPlacebo Group1 Intervention
Each subject will be dosed with placebo for 8 weeks.
Treatment
First Studied
Drug Approval Stage
How many patients have taken this drug
N-Acetyl cysteine
2022
Completed Phase 4
~190

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
N-acetylcysteine (NAC) is an antioxidant that modulates nitric oxide synthases (NOS) and nitric oxide (NO) levels, which are crucial in maintaining brain structure and function. In Neurofibromatosis type 1 (NF1), dysregulated NO can contribute to cognitive, behavioral, and motor impairments. By reducing oxidative stress and normalizing NO levels, NAC helps alleviate these symptoms, offering a targeted approach to managing the neurological complications of NF1. This mechanism is significant for NF1 patients as it addresses the underlying cellular abnormalities contributing to their condition.
Nitric oxide, peroxynitrite and nitroso-compounds formation by ultraviolet A (UVA) irradiated human squamous cell carcinoma: potential role of nitric oxide in cancer prognosis.Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells.Nf1 loss and Ras hyperactivation in oligodendrocytes induce NOS-driven defects in myelin and vasculature.

Find a Location

Who is running the clinical trial?

Children's Hospital Medical Center, CincinnatiLead Sponsor
831 Previous Clinical Trials
6,564,589 Total Patients Enrolled
United States Department of DefenseFED
899 Previous Clinical Trials
332,757 Total Patients Enrolled
1 Trials studying Neurofibromatosis
19 Patients Enrolled for Neurofibromatosis
Carlos E Prada, MDPrincipal InvestigatorChildren's Hospital Medical Center, Cincinnati
2 Previous Clinical Trials
91 Total Patients Enrolled

Media Library

N-Acetyl cysteine (Antioxidant) Clinical Trial Eligibility Overview. Trial Name: NCT04481048 — Phase 2
Neurofibromatosis Research Study Groups: Single Visit/Non-Treatment Arm, N-Acetylcysteine (NAC), Placebo
Neurofibromatosis Clinical Trial 2023: N-Acetyl cysteine Highlights & Side Effects. Trial Name: NCT04481048 — Phase 2
N-Acetyl cysteine (Antioxidant) 2023 Treatment Timeline for Medical Study. Trial Name: NCT04481048 — Phase 2
~12 spots leftby Oct 2025