Open-Label Study of N-Acetylcysteine in Children and Adolescents 5-17 With Bipolar Spectrum Disorders
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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. |
Drug: Open-label Treatment with N-Acetylcysteine
|
Outcome Measures
Primary Outcome Measures
- Mean Change in the Young Mania Rating Scale (YMRS) Score [Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12)]
The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms.
Secondary Outcome Measures
- Mean Change in the Children's Depression Rating Scale (CDRS) Score [Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12)]
The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression.
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Massachusetts General Hospital | Boston | Massachusetts | United States | 02114 |
Sponsors and Collaborators
- Massachusetts General Hospital
Investigators
- Principal Investigator: Janet Wozniak, MD, Massachusetts General Hospital
Study Documents (Full-Text)
More Information
Publications
None provided.- 2014P002011
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Open-Label Treatment With NAC |
|---|---|
| Arm/Group Description | 12-week, open-label treatment with NAC. |
| Period Title: Overall Study | |
| STARTED | 40 |
| Exposed | 26 |
| COMPLETED | 14 |
| NOT COMPLETED | 26 |
Baseline Characteristics
| Arm/Group Title | Open-Label Treatment With NAC |
|---|---|
| Arm/Group Description | 12-week, open-label treatment with NAC. |
| Overall Participants | 26 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
10.0
(3.8)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
14
53.8%
|
| Male |
12
46.2%
|
| Race (NIH/OMB) (Count of Participants) | |
| American Indian or Alaska Native |
1
3.8%
|
| Asian |
0
0%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
| Black or African American |
3
11.5%
|
| White |
19
73.1%
|
| More than one race |
2
7.7%
|
| Unknown or Not Reported |
1
3.8%
|
| Mean Young Mania Rating Scale (YMRS) Score (score on a scale) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [score on a scale] |
23.8
(5.7)
|
| Mean Children's Depression Rating Scale (CDRS) Score (score on a scale) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [score on a scale] |
37.1
(11.7)
|
Outcome Measures
| Title | Mean Change in the Young Mania Rating Scale (YMRS) Score |
|---|---|
| Description | The Young Mania Rating Scale (YMRS) consists of 7 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe) and 4 items rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe).The YMRS score ranges from 0-60. Questions are asked about the last week. A higher score signifies more severe manic symptoms. |
| Time Frame | Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Open-Label Treatment With NAC |
|---|---|
| Arm/Group Description | 12-week, open-label treatment with NAC. |
| Measure Participants | 26 |
| Mean (Standard Deviation) [score on a scale] |
-8.1
(8.5)
|
| Title | Mean Change in the Children's Depression Rating Scale (CDRS) Score |
|---|---|
| Description | The Children's Depression Rating Scale (CDRS) is a clinician-rated instrument with 17 items scored on a 1 to 5 or 1 to 7 scale. A rating of 1 indicates normal, thus the minimum score is 17. The maximum score is 113. Scores of 20-30 suggest borderline depression. Scores of 40-60 indicate moderate depression. |
| Time Frame | Baseline and Endpoint (12 weeks or last observation carried forward if dropped prior to week 12) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Open-Label Treatment With NAC |
|---|---|
| Arm/Group Description | 12-week, open-label treatment with NAC. |
| Measure Participants | 26 |
| Mean (Standard Deviation) [score on a scale] |
-5.2
(10.7)
|
Adverse Events
| Time Frame | 12 weeks | |
|---|---|---|
| Adverse Event Reporting Description | Consistent with good clinical practice, safety will be monitored by each subject's study clinician at each study visit. Subjects will be monitored by the study clinician for adverse events at each visit and adverse events will be recorded on an Adverse Events Form. | |
| Arm/Group Title | Open-Label Treatment With NAC | |
| Arm/Group Description | 12-week, open-label treatment with NAC. | |
All Cause Mortality |
||
| Open-Label Treatment With NAC | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/29 (0%) | |
Serious Adverse Events |
||
| Open-Label Treatment With NAC | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/29 (6.9%) | |
| Psychiatric disorders | ||
| Hospitalization | 1/29 (3.4%) | 1 |
| Mania | 1/29 (3.4%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| Open-Label Treatment With NAC | ||
| Affected / at Risk (%) | # Events | |
| Total | 17/29 (58.6%) | |
| Gastrointestinal disorders | ||
| Nausea/Vomit/Diarrhea | 7/29 (24.1%) | 11 |
| General disorders | ||
| Headache | 3/29 (10.3%) | 3 |
| Dizzy/Lightheaded | 1/29 (3.4%) | 1 |
| Increased Appetite | 1/29 (3.4%) | 3 |
| Thirsty | 1/29 (3.4%) | 3 |
| Infections and infestations | ||
| Cold/Infection/Allergy | 4/29 (13.8%) | 5 |
| Injury, poisoning and procedural complications | ||
| Bike Injury (Stitches) | 1/29 (3.4%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal | 1/29 (3.4%) | 1 |
| Nervous system disorders | ||
| Insomnia | 4/29 (13.8%) | 4 |
| Neurological | 2/29 (6.9%) | 2 |
| Psychiatric disorders | ||
| Anxious/Worried | 2/29 (6.9%) | 2 |
| Dissociation | 1/29 (3.4%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Dermatological | 1/29 (3.4%) | 2 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Janet Wozniak |
|---|---|
| Organization | Massachusetts General Hospital |
| Phone | 617-724-5600 |
| jwozniak@partners.org |
- 2014P002011