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

• Status: Recruiting
• Trial end date: 2024-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Children with neurofibromatosis type 1 (NF1) commonly suffer from the effects of cognitive, behavioral, and motor impairments. At present, there is no specific treatment for this NF1 complication. In this project, the investigators will assess the safety and clinical benefit of N-acetylcysteine (NAC) as a pharmacological intervention in children with NF1. This drug choice is based on the recent findings from mouse models to study the central nervous system manifestations of NF1 at Cincinnati Children's Hospital Medical Center (CCHMC). These findings revealed a role for myelin-forming oligodendrocytes in the control of nitric oxide synthases (NOS) and their product, nitric oxide (NO), in maintenance of brain structure and function, including regulation of behavior and motor control. Treating these mice with NAC corrected cellular and behavioral abnormalities. This data from animal models of NF1 along with uncontrolled clinical observations in children with NF1 suggest that the antioxidant compound, NAC, may reduce these impairments. Therefore, the investigators propose performing a single center double-blind placebo controlled, prospective, Phase II study to explore safety, tolerability, and efficacy of NAC on motor behavior and/or learning in children with NF1 aged 8 through 16 years old. Participants will be carefully monitored for side effects. Primary and secondary outcome measures will be administered at baseline, follow-up, and post-treatment.

• Phase: Phase 2
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborator: United States Department of Defense
• Treatments: Acetylcysteine; N-monoacetylcystine

Criteria

Inclusion Criteria:

• Male and females aged 8 - 16 years (up to 16 years and 6 months) at time of enrollment

• Meets NIH diagnostic criteria for NF1

• Abnormal PANESS study (score at or above the age/sex-based mean)

• Participants must have a full scale intelligence quotient (IQ) of 70 or above, as determined by neurocognitive testing within the last 3 years or during the enrollment process

• Participants on stimulant or any other psychotropic medication should stay on a stable dose (no change in dose) for at least 30 days before entering the study. A stable dose should be maintained throughout the study until completion of all study visits.

Exclusion Criteria:

• Participants should not be receiving chemotherapy currently, or have received chemotherapy in the 6 months prior to entering the study

• Active intracranial lesions (stable low grade glioma is acceptable)

• History of seizure disorder or epilepsy. History of a single seizure that occurred more than 12 months prior to enrollment is acceptable. History of febrile seizures if the last febrile seizure occurred more than 12 months prior to enrollment is acceptable. Recurrent, unprovoked seizures (epilepsy) is sufficient for exclusion.

• Major Depression, Bipolar Disorder, Conduct Disorder, Adjustment Disorder, other major Anxiety Disorders, or other developmental psychiatric diagnoses, based on history

• For females, pregnancy

• Implanted brain stimulator, vagal nerve stimulator, ventriculoperitoneal shunt, cardiac pacemaker, or implanted medication port

• Asthma (bronchospasm has been reported as occurring infrequently and unpredictably when NAC is used as a mucolytic agent)

• High risk of upper gastrointestinal hemorrhage. Examples: presence of esophageal varices or peptic ulcers

• Current use of MEKINIST (MEK-inhibitor) or use within 30 days