Open-Label Study of N-Acetylcysteine in Children and Adolescents 5-17 With Bipolar Spectrum Disorders

NCT ID: NCT02357290

Last Updated: 2019-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2018-09-24

Brief Summary

Children between the ages of 5-17 years old who have or display symptoms of emotional dysregulation (explosiveness, mood swings, irritability, and/or violent behavior) are invited to participate in a 12-week research study to determine the effectiveness and safety of the natural treatment N-acetylcysteine (NAC) for children with emotional and behavioral problems. After undergoing a comprehensive evaluation by medical doctors with a specialty in this area, children who are found eligible to participate in this research study will be treated with NAC. Following the evaluation period, this research study requires 12 weekly visits, either in our office or over the phone, in an effort to closely monitor each child's response to the medication. Eligible participants will receive study-related evaluations and weekly study visits with our study doctors at no cost.

Detailed Description

This will be a 12-week, open-label study of NAC in the treatment of bipolar disorder in children and adolescents. Subjects will include youth ages 5-17 years with a bipolar spectrum disorder (type I, II, or NOS), mixed, manic, or hypomanic state, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition DSM-5 (American Psychiatric Association, 2013). The primary outcome measures will be improvement in manic symptoms as measured by the Young Mania Rating Scale (YMRS) and improvement in depressive symptoms as measured by the Child Depression Rating Scale (CDRS).

Bipolar diagnoses will be made according to the DSM-5 in a clinical evaluation by a Child Psychiatrist and confirmed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children - Epidemiological Version (K-SADS-E)(Orvaschel, 1994). All subjects must have a YMRS score of at least 15. Only patients who are not responding to their current treatment regimen will be tapered from their medications; youth on concomitant psychiatric medications will be permitted to continue those medications as listed in the concomitant medication section.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Open-label Treatment with NAC

12-week, open-label treatment with NAC. Subjects will be treated with the following dose:

Subjects ages 5-12:

Week 1: 900mg po daily Weeks 2+: 900mg po QAM, 900mg po QPM

Subjects ages 13-17:

Week 1: 900mg po daily Weeks 2-3: 900mg po QAM, 900mg po QPM Weeks 4+: 1800mg po QAM, 900mg po QPM

In Weeks 3-12 for subjects ages 13-17, we will encourage twice per day dosing, but we will permit daily dosing if needed for adherence.

Group Type: EXPERIMENTAL

Open-label Treatment with N-Acetylcysteine

Intervention Type: DRUG

Interventions

Open-label Treatment with N-Acetylcysteine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female subjects, 5-17 years of age
• Subjects must have a DSM-IV diagnosis of a bipolar spectrum disorder (type I, II, or Not Otherwise Specified) and currently display mixed, manic, or hypomanic symptoms (without psychotic features) according to clinical assessment based on the DSM-IV and confirmed with structured diagnostic interview
• Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator and to cooperate with all tests and examinations required by the protocol
• Subjects and their legal representatives must be considered reliable.
• Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must provide written consent and the subject must provide written assent.
• Subjects must have an initial score on the YMRS of at least 15.

Exclusion Criteria

• Investigator and his/her immediate family (defined as the investigator's spouse, parent, child, grandparent, or grandchild)
• Serious or unstable illness including hepatic, rental, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease
• Uncorrected hypothyroidism or hyperthyroidism
• History of sensitivity to N-acetylcysteine, a history of intolerance to N-acetylcysteine, or a non-responder after 2 months of treatment at adequate doses as determined by the clinician
• Severe allergies or multiple adverse drug reactions
• Current or past history of seizures
• Active substance abusers, per clinician judgment
• Judged clinically to be at serious suicidal risk
• Current diagnosis of schizophrenia
• Pregnancy
• C-SSRS score ≥ 4
• IQ < 70

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Janet Wozniak, MD

Associate Professor of Psychiatry, Harvard Medical School; Medical Director, Child and Adolescent Outpatient Psychiatry Services; Director, Pediatric Bipolar Clinical and Research Program in Pediatric Psychopharmacology, Massachusetts General Hospital

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Janet Wozniak, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Wozniak J, DiSalvo M, Farrell A, Vaudreuil C, Uchida M, Ceranoglu TA, Joshi G, Cook E, Faraone SV, Biederman J. Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania. BMC Psychiatry. 2022 May 3;22(1):314. doi: 10.1186/s12888-022-03943-x.

Reference Type: DERIVED

PMID: 35505312 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2014P002011

Identifier Type: -

Identifier Source: org_study_id