Trial Outcomes & Findings for Antioxidant Therapy With N-acetylcysteine for Learning and Motor Behavior in Children With Neurofibromatosis Type 1 (NCT NCT04481035)

Last Updated: 2025-07-31

Results Overview

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preliminary data suggest may demonstrate more extreme problems in children with NF1 than age-matched healthy controls (unpublished data from CCHMC).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).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

5 participants

Primary outcome timeframe

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).

Results posted on

2025-07-31

Participant Flow

Participant milestones

Participant milestones
Measure	N-Acetylcysteine Followed by Placebo 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, followed by placebo three times per day for 8 weeks.	Placebo Followed by N-Acetylcysteine Participants will be dosed three times per day with a placebo for eight (8) weeks followed by 70 mg/kg/dose (max dose 900 mg) three times per day of N-Acetylcysteine for 8 weeks.
Period 1 STARTED	3	2
Period 1 COMPLETED	3	2
Period 1 NOT COMPLETED	0	0
Period 2 STARTED	3	2
Period 2 COMPLETED	3	2
Period 2 NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 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).

Population: Descriptive only

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=5 Participants 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. N-acetylcysteine (NAC): The study design is essentially a cross-sectional survey and then longitudinal evaluation of cognition and behavior, motor function, cortical function, and metabolomics profiles in NF1 before and after 8 weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC) or placebo. This is a cross-over double-blind placebo controlled study. Participants in the experimental phase/arm will receive 70 mg/kg/dose (max dose 900 mg) three times per day of NAC for eight (8) weeks.	Placebo n=5 Participants 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. Placebo: The study design is essentially a cross-sectional survey and then longitudinal evaluation of cognition and behavior, motor function, cortical function, and metabolomics profiles in NF1 before and after 8 weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC) or placebo. This is a cross-over double-blind placebo controlled study. Participants in the placebo phase/arm will receive placebo (non-drug) three times per day for eight (8) weeks.
Change From Baseline in Motor Function Measured by Physical and Neurological Examination for Subtle Signs (PANESS)	0 score on a scale Interval -8.0 to 2.0	3 score on a scale Interval -4.0 to 25.0

PRIMARY outcome

Population: Modified ITT - all participants who received at least one dose of study drug

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 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).

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=5 Participants 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. N-acetylcysteine (NAC): The study design is essentially a cross-sectional survey and then longitudinal evaluation of cognition and behavior, motor function, cortical function, and metabolomics profiles in NF1 before and after 8 weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC) or placebo. This is a cross-over double-blind placebo controlled study. Participants in the experimental phase/arm will receive 70 mg/kg/dose (max dose 900 mg) three times per day of NAC for eight (8) weeks.	Placebo n=5 Participants 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. Placebo: The study design is essentially a cross-sectional survey and then longitudinal evaluation of cognition and behavior, motor function, cortical function, and metabolomics profiles in NF1 before and after 8 weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC) or placebo. This is a cross-over double-blind placebo controlled study. Participants in the placebo phase/arm will receive placebo (non-drug) three times per day for eight (8) weeks.
Change From Baseline in ADHD Symptoms as Reported Via Parent/Teacher Surveys	-12.5 units on a scale Standard Deviation 13.1	-3.75 units on a scale Standard Deviation 12.0

SECONDARY outcome

Population: modified ITT - at least one dose given

Transcranial Magnetic Stimulation (TMS) - Cortical Silent Period (CSP). This measure describes the function and physiology of the motor system using Transcranial Magnetic Stimulation (TMS) over the brain to evoke a muscle twitch in the hand. These evoked potentials provide information about the instantaneous balance of excitation and inhibition in the brain, which in turn relate in part to neurotransmitter levels that can be altered by diseases and by treatments. This measure reflects an inhibitory neurotransmitter called GABA-B and its action at a particular receptor - the "GABA B" receptor. A lengthening of the duration of CSP indicates more inhibition, which is good (within a healthy range of approximately 50 to 150 ms, because outside of that range is abnormal). Here we report the average difference before and after treatment.

Outcome measures

Outcome measures
Measure	N-Acetylcysteine n=5 Participants 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. N-acetylcysteine (NAC): The study design is essentially a cross-sectional survey and then longitudinal evaluation of cognition and behavior, motor function, cortical function, and metabolomics profiles in NF1 before and after 8 weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC) or placebo. This is a cross-over double-blind placebo controlled study. Participants in the experimental phase/arm will receive 70 mg/kg/dose (max dose 900 mg) three times per day of NAC for eight (8) weeks.	Placebo n=5 Participants 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. Placebo: The study design is essentially a cross-sectional survey and then longitudinal evaluation of cognition and behavior, motor function, cortical function, and metabolomics profiles in NF1 before and after 8 weeks of treatment with an FDA approved medication, N-acetylcysteine (NAC) or placebo. This is a cross-over double-blind placebo controlled study. Participants in the placebo phase/arm will receive placebo (non-drug) three times per day for eight (8) weeks.
Transcranial Magnetic Stimulation (TMS) - Cortical Silent Period	6 ms Standard Deviation 19	-4 ms Standard Deviation 18

SECONDARY outcome

The investigators propose to evaluate the autotaxin/LPC axis. High autotaxin levels correlate with a worse outcome. Low lysophosphatidylcholine (LPC) levels correlate to a worse outcome. The investigators will collect serum and plasma from participants to assess autotaxin/LPC axis prior and post-NAC therapy. We will perform serum targeted analysis for LPC, autotaxin activity and LPA measurements pre and post-treatment. We will perform a highly specific mass spectrometry target analysis of LPC species from serum for clinical correlation. We will use authentic standards to accurately measure low and high levels of these biomarkers. We will quantify autotaxin enzyme activity using a fluorometric assay to correlate with LPC measurements. We will quantify LPA using serum ELISA kit. Data is not yet available as the samples in storage for follow up study.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

In the same cohort, to evaluate metabolomics profiles as a possible disease biomarker that is affected by NF1 and by treatment with NAC as per Aim 1. Hypothesis 4: The investigators hypothesize that specific profiles will predict clinical response to antioxidant therapy compared to age-matched healthy control (unpublished data from CCHMC).

Outcome measures

Outcome data not reported

Adverse Events

N-Acetylcysteine Treatment

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Donald L. Gilbert MD

Cincinnati Children's Hospital Medical Center

Phone: 513-636-4222

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	N-Acetylcysteine Followed by Placebo n=3 Participants 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, followed by placebo three times per day for 8 weeks.	Placebo Followed by N-Acetylcysteine n=2 Participants Participants will be dosed three times per day with a placebo for eight (8) weeks followed by 70 mg/kg/dose (max dose 900 mg) three times per day of N-Acetylcysteine for 8 weeks.	Total n=5 Participants Total of all reporting groups
Age, Continuous	13 years n=5 Participants	14.5 years n=7 Participants	13 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Physical and Neurological Examination for Subtle Signs (PANESS) Total	45 units on a scale STANDARD_DEVIATION 11 • n=5 Participants	38 units on a scale STANDARD_DEVIATION 4.2 • n=7 Participants	42 units on a scale STANDARD_DEVIATION 8.7 • n=5 Participants
Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS), DuPaul DSM-5 based scale	35 units on a scale STANDARD_DEVIATION 5.4 • n=5 Participants	51 units on a scale STANDARD_DEVIATION 0 • n=7 Participants	39 units on a scale STANDARD_DEVIATION 8.3 • n=5 Participants