Cornelia de Lange SyndromePhase 2NCT04381897

Use of N-Acetylcysteine in the Treatment of Repetitive and Self-Injurious Behaviors in Cornelia de Lange Syndrome

A Phase 2 study testing N-acetyl cysteine in people with Cornelia de Lange Syndrome, run by Johns Hopkins University at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

Search all trials

Trial summary

This research project is a randomized cross-over pilot trial which aims to test the efficacy of N-acetylcysteine (NAC) for the treatment of Repetitive Behaviors (RB) and self-injurious behavior (SIB) in patients with Cornelia de Lange Syndrome (CdLs). Read more about this study

Who is it for?: Ages 13 to 35 years
Conditions the study is for: Cornelia de Lange Syndrome
What is being tested?: N-acetyl cysteine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 10 participants
Where: 1 siteUnited States
Study dates: 1 Nov 2026to 1 May 2027
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 13 to 35 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

Ages 13 to 35 years
A diagnosis of CdLS as determined by a physician during routine care meeting the major and minor criteria from CdLS guidelines
Threshold criteria for the presence of RB/SIB as reported on initial screening Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CYBOCS-PDD) > 6 OR Aberrant Behavior Checklist (ABC) stereotypy subscale > 7)
Being able to attend 4 visits over the course of 18 weeks at the Johns Hopkins Hospital
No acute safety concerns or need for hospitalization due to psychotic, manic or depressive episode
Not currently pregnant or lactating/breastfeeding. Whether a participant is pregnant or not will be determined by the participant/caregiver report based on date last menses. If there is any suspicion of pregnancy, the PI will confer with the family to obtain testing through the primary care provider.

Who cannot join

Allergy to NAC
Allergy to Quinine
Contraindication to NAC (organ transplant; untreated or symptomatic gastric condition)
Need for another medication with which NAC is contraindicated (antibiotics)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Masoud Salehi, M.D. contact

443-857-9365

msalehi3@jhmi.edu

United States1 site

Johns Hopkins University School of Medicine
Baltimore, Maryland, 21205
Masoud Salehi, MD, 443-857-9365, msalehi3@jhmi.edu
Marco A Grados, MD, PHD

Other trials in United States

About this study

Official title: Use of N-Acetylcysteine (NAC) in the Treatment of Repetitive Behaviors (RB) and Self-Injurious Behaviors (SIB) in Cornelia de Lange Syndrome: A Randomized Double-Blind Placebo-Controlled Pilot Study

NAC is a known anti-oxidative stress and neuroprotective agent, which has been shown to decrease the occurrence of SIB such as skin picking. NAC has also shown partial response in trials for compulsive behaviors in Obsessive Compulsive Disorder (OCD) and related disorders in autism.

Cornelia de Lange syndrome (CdLS) is a genetic disorder with autistic features, including RBs and SIB. In this randomized clinical trial, participants with CdLS will be blindly assigned one of two possible treatment arms: 1) placebo (8 weeks) and NAC (8 weeks); or 2) NAC (8 weeks) and placebo (8 weeks), with an intermediate 2-week washout period.

Read the detailed description

Cornelia de Lange syndrome (CdLS) is a genetic condition caused by mutations in cohesin-related genes, mostly notably NIPBL. The CdLS phenotype includes physical features such as typical facies, limb abnormalities, short stature, and hirsutism as well developmental and behavioral manifestations such as intellectual disability, communication deficits, autistic traits and repetitive/self-injurious behaviors (RBs/SIB).

Behavioral challenges such as RBs/SIB pose a significant obstacle to quality of life to individuals with CdLS and families. In CdLS, disruption of developmental systems can impact neuronal and brain development, and impact GABAergic inhibitory interneuron formation, leading to RBs/SIB. Given the potential for dysregulated excitatory glutamatergic output in CdLS, neuronal oxidative stress may play a role in these maladaptive behaviors. NAC replenishes Central Nervous System (CNS) glutathione, a potent antioxidant and may ameliorate RBs/SIB. NAC has been shown to decrease maladaptive behaviors in autism and grooming disorders such as excoriation disorder (skin picking).

An 18-week cross-over trial is proposed to decrease RBs/SIB comprising two 8-week double-blinded active or placebo treatment with a 2-week wash out period in between. A cross-over design will afford for higher efficiency in sample size for similar power. Dosage will be titrated weekly starting at 600 mg daily and then increased by 600 mg every week to a target dose of 1800 mg per day. Participants will be recruited through CdLS Foundation.

Based on a mechanism for regulation glutamate transmission homeostasis in the central nervous system, the use of NAC may be particularly pertinent to individuals with CdLS. It is known that in CdLS genetic networks that impact on limb formation overlap significantly with developmental systems that impact neuronal and brain development, in particular GABAergic inhibitory interneuron formation. Given a dysregulated excitatory glutamatergic mechanism due to interneuron deficits, which can then lead to neuronal oxidative stress and programmed cell death, NAC may act as a key homeostatic regulator to prevent glutamate overactivity and neuronal damage in CdLS.

Conditions: Cornelia de Lange Syndrome
Being tested: N-acetyl cysteine, Placebo
Keywords: Repetitive behaviors, Self-injurious behavior, N-acetylcysteine, Genetic disorder, Children, Psychiatric disease
Medical subject headings: De Lange Syndrome, Self-Injurious Behavior, Genetic Diseases, Inborn, Mental Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

N-acetyl cysteineDrug
Also called Acetylcysteine, National Drug Code (NDC): 63323-690
Oral solution for N-acetyl cysteine is prepared in syringes and provided to the participants along with instructions on how to administer them.
PlaceboOther
NAC Placebo-matching solution is prepared in syringes and provided to the participants along with instructions on how to administer them.

Study groups in NCT04381897
Study group	Role	What they receive
Group A: NAC 1800mg then Placebo	Experimental	NAC 1800 milligrams (mg), oral solution, every 8 hours for 8 weeks, followed by a 2-week wash-out period, followed by NAC Placebo-matching solution, orally every 8 hours, for 8 weeks. Dosage will be titrated weekly starting at 600 mg daily and then increased by 600 mg every week to a target dose of 1800 mg per day. Receives: Drug: N-acetyl cysteine; Other: Placebo
Group B: Placebo then NAC 1800mg	Experimental	NAC Placebo-matching solution, orally every 8 hours, for 8 weeks, followed by a 2-week wash-out period, followed by NAC 1800 milligrams (mg), oral solution, every 8 hours for 8 weeks. Dosage will be titrated weekly starting at 600 mg daily and then increased by 600 mg every week to a target dose of 1800 mg per day. Receives: Drug: N-acetyl cysteine; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CYBOCS-PDD) repetitive behaviors measure score
CYBOCS-PDD scores range from a minimum of 0 to a maximum of 20, higher scores indicate greater symptom severity. Efficacy of the intervention would be assessed by ≥35% reduction in CYBOCS-PDD repetitive behaviors measure score.
Measured: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18
Change in Aberrant Behavior Checklist (ABC) irritability self-injurious behaviors items score
The ABC irritability sub-scale consists of 15 items of which 3 focus on Self-injurious Behaviors (SIB). Each item takes scores ranging from a minimum of 0 to a maximum of 3. The overall score for the SIB items would range from 0 to 9 with higher scores indicating greater symptom severity. Efficacy of the intervention in reducing self-injurious behaviors would be assessed by a ≥35% reduction in ABC irritability SIB items sub-scale score.
Measured: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18

Secondary outcomes (8)

Change in Aberrant Behavior Checklist (ABC) irritability non-injurious behaviors items score
The ABC irritability sub-scale consists of 15 items of which 12 focus on depressed mood and irritable behaviors (non-injurious behaviors). Each item takes a score ranging from a minimum of 0 to a maximum of 3. The overall score for the non-injurious behavior items would range from 0 to 36 with higher scores indicating greater symptom severity. Efficacy of the intervention in reducing depressed mood and irritability would be assessed by a ≥35% score reduction in ABC irritability non-injurious behavior items of sub-scale.
Measured: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18
Change in total score of Parenting Stress Index/Short Form (PSI/SF)
The PSI-SF is a 36-item questionnaire designed to measure stress in the parent-child system and identify those families most in need of follow-up services. The PSI-SF consists of three sub-scales: Parental Distress, Parent-Child Dysfunctional Interaction, and Difficult Child. Each sub-scale consists of 12 items rated from 1 (strongly disagree) to 5 (strongly agree). Sub-scale scores therefore range from 12 to 60, whereas the total score ranges from 36 to 180. High scores on the PSI-SF total score indicate greater levels of stress.
Measured: Baseline, week 8, week 10, week 18
Change in Burden Scale for Family Caregivers score
Burden Scale for Family Caregivers, for assessing subjective burden in informal caregivers. It consists of 10 items, each ranging from 0 to 3, with total score ranging from 0 to 30. High scores indicate greater levels of burden in caregiver.
Measured: Baseline, week 8, week 10, week 18
Change in Sensory Profile score
Sensory profile measure identifies sub-types of individuals based on sensory processing patterns and categorize it as one of the following five profiles: 1- Balanced; 2- Interested; 3- Intense; 4- Mellow until ... ; and 5- Vigilant.
Measured: Baseline, week 8, week 10, week 18
Change in Childhood Autism Rating Scale (CARS2) score
The Childhood Autism Rating Scale-Second Edition (CARS2) is a 15-item rating scale used to identify children with autism and distinguishing them from those with developmental disabilities. The 15 items can take 4 scores where 1 stands for normal for child's age, 2 for mildly abnormal, 3 for moderately abnormal and 4 for severely abnormal. Scores range form 15 to 60 with 30 being the cutoff rate for a diagnosis of mild autism. Scores 30-37 indicate mild to moderate autism, while scores between 38 and 60 are characterized as severe autism.
Measured: Baseline, week 8, week 10, week 18
Change in Vineland adaptive Behavior Scale (VABS) score
VABS is a parent interview that provides standard scores (100±15 adjusted for age and gender) for communication, socialization, and daily living.
Measured: Baseline, week 8, week 10, week 18
Change in Clinical Global Impression - Severity of Illness (CGI-S) score
CGI-S asks the clinician one question: "Considering your total clinical experience with this particular population, how mentally ill is the patient at this time?" which is rated on the following seven-point scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days. Clearly, symptoms and behavior can fluctuate over a week; the score should reflect the average severity level across the seven days.
Measured: Baseline, week 8, week 10, week 18
Change in Side Effects Survey
A previously used side effect tracker is implemented for measuring patient/caregiver-reported side effects of medication. It consists of 14 side effects of interest which each may take scores ranging from 1 defined as "Not reported" through 5 defined as "Disabling".
Measured: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Nov 20261 May 2027

First posted11 May 2020
Study start1 Nov 2026 (estimated)
Primary completion1 May 2027 (estimated)
Study completion1 May 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Cornelia de Lange SyndromeStudies of the same condition, open and under way.
More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 10 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04381897
Sponsor's protocol ID: IRB00153778
Status last verified: Aug 2026
First submitted: 6 May 2020
Last updated: 14 Aug 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam R. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014. Epub 2012 Feb 18.
PubMed 22342106

Interested in taking part?

Masoud Salehi, M.D.

443-857-9365

msalehi3@jhmi.edu

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Recruiting
Behavioral Assessment and Treatment of Problem Behavior in Children With Cornelia de Lange Syndrome
Cornelia de Lange Syndrome
RecruitingPhase 2/3
Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
Cornelia De Lange Syndrome
RecruitingObservational study
GROWing Up With Rare GENEtic Syndromes
Prader-Willi Syndrome, PWS-like Syndrome

All Cornelia de Lange Syndrome trials

Study at a glance

From the registry record, last updated by the sponsor on 14 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Use of N-Acetylcysteine (NAC) in the Treatment of Repetitive Behaviors (RB) and Self-Injurious Behaviors (SIB) in Cornelia de Lange Syndrome: A Randomized Double-Blind Placebo-Controlled Pilot Study
ClinicalTrials.gov ID: NCT04381897
Acronym / sponsor ID: IRB00153778
Conditions: Cornelia de Lange Syndrome
Keywords: Repetitive behaviors, Self-injurious behavior, N-acetylcysteine, Genetic disorder, Children, Psychiatric disease
Phase: Phase 2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 10 participants (estimated)
Lead sponsor: Johns Hopkins UniversityUniversity, hospital or other
Collaborators: Cornelia de Lange Syndrome Foundation
Study start: 1 Nov 2026 (estimated)
Primary completion: 1 May 2027 (estimated)
Study completion: 1 May 2027 (estimated)
First posted: 11 May 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Group A: NAC 1800mg then Placebo	Experimental	Drug: N-acetyl cysteine, Other: PlaceboNAC 1800 milligrams (mg), oral solution, every 8 hours for 8 weeks, followed by a 2-week wash-out period, followed by NAC Placebo-matching solution, orally every 8 hours, for 8 weeks. Dosage will be titrated weekly starting at 600 mg daily and then increased by 600 mg every week to a target dose of 1800 mg per day.
Group B: Placebo then NAC 1800mg	Experimental	Drug: N-acetyl cysteine, Other: PlaceboNAC Placebo-matching solution, orally every 8 hours, for 8 weeks, followed by a 2-week wash-out period, followed by NAC 1800 milligrams (mg), oral solution, every 8 hours for 8 weeks. Dosage will be titrated weekly starting at 600 mg daily and then increased by 600 mg every week to a target dose of 1800 mg per day.

Who may qualify

Ages: 13 to 35 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (6 listed)

Ages 13 to 35 years
A diagnosis of CdLS as determined by a physician during routine care meeting the major and minor criteria from CdLS guidelines
Threshold criteria for the presence of RB/SIB as reported on initial screening Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CYBOCS-PDD) > 6 OR Aberrant Behavior Checklist (ABC) stereotypy subscale > 7)
Being able to attend 4 visits over the course of 18 weeks at the Johns Hopkins Hospital
No acute safety concerns or need for hospitalization due to psychotic, manic or depressive episode

Key exclusion criteria (4 listed)

Allergy to NAC
Allergy to Quinine
Contraindication to NAC (organ transplant; untreated or symptomatic gastric condition)
Need for another medication with which NAC is contraindicated (antibiotics)

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
N-acetyl cysteineAlso: Acetylcysteine, National Drug Code (NDC): 63323-690Oral solution for N-acetyl cysteine is prepared in syringes and provided to the participants along with instructions on how to administer them.	Drug	Group A: NAC 1800mg then Placebo, Group B: Placebo then NAC 1800mg
PlaceboNAC Placebo-matching solution is prepared in syringes and provided to the participants along with instructions on how to administer them.	Other	Group A: NAC 1800mg then Placebo, Group B: Placebo then NAC 1800mg

Primary outcome

Change in Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CYBOCS-PDD) repetitive behaviors measure score
Time frame: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18
CYBOCS-PDD scores range from a minimum of 0 to a maximum of 20, higher scores indicate greater symptom severity. Efficacy of the intervention would be assessed by ≥35% reduction in CYBOCS-PDD repetitive behaviors measure score.
Change in Aberrant Behavior Checklist (ABC) irritability self-injurious behaviors items score
Time frame: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18
The ABC irritability sub-scale consists of 15 items of which 3 focus on Self-injurious Behaviors (SIB). Each item takes scores ranging from a minimum of 0 to a maximum of 3. The overall score for the SIB items would range from 0 to 9 with higher scores indicating greater symptom severity. Efficacy of the intervention in reducing self-injurious behaviors would be assessed by a ≥35% reduction in ABC irritability SIB items sub-scale score.

8 secondary outcomes

Change in Aberrant Behavior Checklist (ABC) irritability non-injurious behaviors items score
Time frame: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18
Change in total score of Parenting Stress Index/Short Form (PSI/SF)
Time frame: Baseline, week 8, week 10, week 18
Change in Burden Scale for Family Caregivers score
Time frame: Baseline, week 8, week 10, week 18
Change in Sensory Profile score
Time frame: Baseline, week 8, week 10, week 18
Change in Childhood Autism Rating Scale (CARS2) score
Time frame: Baseline, week 8, week 10, week 18
Change in Vineland adaptive Behavior Scale (VABS) score
Time frame: Baseline, week 8, week 10, week 18
Change in Clinical Global Impression - Severity of Illness (CGI-S) score
Time frame: Baseline, week 8, week 10, week 18
Change in Side Effects Survey
Time frame: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 14 Aug 2026.
Background: PubMed 22342106Hardan AY, Fung LK, Libove RA, Obukhanych TV, Nair S, Herzenberg LA, Frazier TW, Tirouvanziam R. A randomized controlled pilot trial of oral N-acetylcysteine in children with autism. Biol Psychiatry. 2012 Jun 1;71(11):956-61. doi: 10.1016/j.biopsych.2012.01.014. Epub 2012 Feb 18.
Individual participant dataSharing planned: No

Related trials for Cornelia de Lange Syndrome

RecruitingObservational study
Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Rare Disorders, Undiagnosed Disorders
Recruiting
Behavioral Assessment and Treatment of Problem Behavior in Children With Cornelia de Lange Syndrome
Cornelia de Lange Syndrome
RecruitingPhase 2/3
Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
Cornelia De Lange Syndrome
RecruitingObservational study
GROWing Up With Rare GENEtic Syndromes
Prader-Willi Syndrome, PWS-like Syndrome

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Masoud Salehi, M.D. contact

443-857-9365

msalehi3@jhmi.edu

Marco A Grados, M.D., M.P.H. principal investigator

Department of Psychiatry & Behavioral Sciences, Johns Hopkins School of Medicine

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing N-acetyl cysteine in people with Cornelia de Lange Syndrome, run by Johns Hopkins University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Masoud Salehi, M.D. (443-857-9365, msalehi3@jhmi.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Children's Yale-Brown Obsessive Compulsive Scale Modified for Pervasive Developmental Disorders (CYBOCS-PDD) repetitive behaviors measure score (time frame: Baseline, week 2, week 4, week 6, week 8, week 10, week 12, week 14, week 16, week 18). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04381897, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Aug 2026.