58 Participants Needed

Antioxidant Therapy for Neurofibromatosis Type 1

(DoDNAC Trial)

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Overseen ByDonald L Gilbert, MD MS
Age: < 18
Sex: Any
Trial Phase: Phase 2
Sponsor: Children's Hospital Medical Center, Cincinnati
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

If you are taking stimulant or psychotropic medications, you need to stay on a stable dose for at least 30 days before joining the study and keep that dose during the study. If you are using antidepressants, dopamine blocking agents, or mood stabilizers, you cannot participate in the trial.

What evidence supports the effectiveness of the drug N-Acetyl cysteine (NAC) for treating Neurofibromatosis Type 1?

Research suggests that oxidative stress plays a role in the development of tumors in Neurofibromatosis Type 1 (NF1), and NAC is known to help reduce oxidative stress. Although not directly tested for NF1, NAC's ability to balance oxidative stress may offer potential benefits for managing NF1-related conditions.12345

Is N-Acetyl cysteine (NAC) safe for use in humans?

N-Acetyl cysteine (NAC) has been studied for its ability to reduce oxidative damage and side effects of chemotherapy in pediatric cancer models, suggesting it is generally safe for use in humans.12367

How does the drug N-Acetyl cysteine (NAC) differ from other treatments for Neurofibromatosis Type 1?

N-Acetyl cysteine (NAC) is unique because it is an antioxidant that aims to reduce oxidative stress, which is a different approach compared to other treatments that may not target oxidative stress directly. This drug is also used in other conditions to protect cells from damage, which highlights its potential to address underlying cellular issues in Neurofibromatosis Type 1.6891011

Research Team

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Donald Gilbert, MD MS

Principal Investigator

Children's Hospital Medical Center, Cincinnati

Eligibility Criteria

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.

Inclusion Criteria

You have an abnormal PANESS score.
I have been diagnosed with neurofibromatosis type 1.
I have been on a stable dose of my psychiatric medication for at least 30 days.
See 2 more

Exclusion Criteria

I have epilepsy.
I have a stable low-grade brain tumor or epilepsy.
For females, pregnancy
See 11 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N-acetylcysteine (NAC) or placebo for 8 weeks to assess safety, tolerability, and efficacy on motor behavior and neurocognitive symptoms

8 weeks
Visits at weeks 0, 8, and 12

Washout

Participants undergo a 4-week washout period after treatment to assess the persistence of NAC effects

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks
Visit at week 12

Treatment Details

Interventions

  • N-Acetyl cysteine
  • Placebo
Trial OverviewThe 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.
Participant Groups
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.

N-Acetyl cysteine is already approved in United States, European Union for the following indications:

🇺🇸
Approved in United States as NAC for:
  • Antidote for acetaminophen overdose
  • Mucolytic agent
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Approved in European Union as NAC for:
  • Antidote for paracetamol overdose
  • Mucolytic agent

Find a Clinic Near You

Who Is Running the Clinical Trial?

Children's Hospital Medical Center, Cincinnati

Lead Sponsor

Trials
844
Recruited
6,566,000+

United States Department of Defense

Collaborator

Trials
940
Recruited
339,000+

References

Dynamic thiol/disulphide homeostasis in children with neurofibromatosis type 1 and tuberous sclerosis. [2020]
The Contribution of Oxidative Stress to NF1-Altered Tumors. [2023]
Peroxynitrite supports a metabolic reprogramming in merlin-deficient Schwann cells and promotes cell survival. [2021]
Tumor growth of neurofibromin-deficient cells is driven by decreased respiration and hampered by NAD+ and SIRT3. [2022]
Combining APR-246 and HDAC-Inhibitors: A Novel Targeted Treatment Option for Neuroblastoma. [2021]
N-acetylcysteine chemoprotection without decreased cisplatin antitumor efficacy in pediatric tumor models. [2018]
Metabolic activation and genotoxicity of N-hydroxy-2-acetylaminofluorene and N-hydroxyphenacetin derivatives in Reuber (H4-II-E) hepatoma cells. [2013]
A Phase II Randomized Placebo-Controlled Trial of Oral N-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress In Vivo. [2021]
Use of oral N-acetylcysteine for protection of melanocytic nevi against UV-induced oxidative stress: towards a novel paradigm for melanoma chemoprevention. [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Antioxidants accelerate lung cancer progression in mice. [2022]
Antioxidants Promote Intestinal Tumor Progression in Mice. [2021]