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

NCT04381897 | Not Yet Recruiting Phase 2 FDA Drug

• 1 other identifier: IRB00153778
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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). 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.

Conditions

Cornelia de Lange Syndrome

Keywords

Repetitive behaviors; Self-injurious behavior; N-acetylcysteine; Genetic disorder; Children; Psychiatric disease

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  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

  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)

  Baseline, week 8, week 10, week 18

• Change in Burden Scale for Family Caregivers score

  Baseline, week 8, week 10, week 18

• Change in Sensory Profile score

  Baseline, week 8, week 10, week 18

• Change in Childhood Autism Rating Scale (CARS2) score

  Baseline, week 8, week 10, week 18

Study Arms (2)

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.

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.

Drug: N-acetyl cysteine; Other: Placebo

Interventions

N-acetyl cysteine DRUG

Oral solution for N-acetyl cysteine is prepared in syringes and provided to the participants along with instructions on how to administer them.

Also known as: Acetylcysteine, National Drug Code (NDC): 63323-690

Group A: NAC 1800mg then Placebo; Group B: Placebo then NAC 1800mg

Placebo OTHER

NAC Placebo-matching solution is prepared in syringes and provided to the participants along with instructions on how to administer them.

Group A: NAC 1800mg then Placebo; Group B: Placebo then NAC 1800mg

Eligibility Criteria

• Age: 13 Years - 35 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Johns Hopkins University: lead
• Cornelia de Lange Syndrome Foundation: collaborator

Study Sites (1)

Johns Hopkins University School of Medicine

Baltimore, Maryland, 21205, United States

Location

Related Publications (1)

• 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.

  PMID: 22342106 BACKGROUND

MeSH Terms

Conditions

De Lange Syndrome; Self-Injurious Behavior; Genetic Diseases, Inborn; Mental Disorders

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Marco A Grados, M.D., M.P.H.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Masoud Salehi, M.D.

CONTACT

443-857-9365; msalehi3@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 11, 2020
• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)