8-Week Double-Blind, Randomized Controlled Study of N-Acetylcysteine and Neuroimaging in Children Ages 6-12 With Emotional Dysregulation
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 2
- 主要终点
- Mean Change in the Clinician-Young Mania Rating Scale (C-YMRS) Score
研究概览
简要总结
This is a double-blind randomized controlled study. The study will last up to 16 weeks from the initial phone screen (it could take up to eight weeks to schedule and complete the initial screening process and schedule the 2 MRI visits). Once subjects have completed the screening process, they will begin the 8-week trial phase. Subjects will be assessed weekly throughout the study for efficacy and tolerability.
The investigators plan to recruit 80 participants with emotional dysregulation (ED) in the treatment arm. In addition, the investigators will aim to recruit 40age-, sex-, and parental-education matched participants without emotional dysregulation, and major psychopathology as Typically Developing (TD) control participants in the control arm.
Upon scheduling the baseline visit, only the emotional dysregulation (ED) participants will be randomized 1:1 to be exposed to NAC or placebo treatment for 8 weeks. Participants will complete baseline and post-treatment (endpoint) brain MRI acquisition. TD participants will complete the same screening and characterization process as the ED group and then will be invited to complete MRI eligibility screening and to be scanned twice, separated by an eight-week interval, but the TD will not complete the NAC treatment or receive a placebo. See Table 1 (Study Schema) for a complete list of characterization measures to be completed by each group.
详细描述
The investigators will enroll 120 subjects. Participants will be 80 children with emotion dysregulation, 6-12 years of age. In addition, the investigators will include 40 children without emotion dysregulation as healthy controls to provide a normative comparison group for neuroimaging analyses.
All subjects that enter the study will undergo standard screening and diagnostic procedures. Individuals who express interest in the study, either by responding to advertising or by giving a referring clinician explicit permission to be contacted for research, will be screened for eligibility by the study coordinator or a research assistant via phone. If the interested youth meet criteria for either the ED or TD group, the parent/guardian will be asked to complete the Child Behavior Checklist (CBCL) online via RedCap, a secure online data capture system.
The study coordinator will send a link to complete the CBCL electronically to the parent/guardian via email. An online consent statement will appear, prompting parents to indicate their agreement to participate in the online questionnaire portion of the study. If the parent/guardian indicates their agreement, the data capture system will proceed to the CBCL.
After completing the CBCL, eligible participants based on inclusion and exclusion criteria will either be assigned to the ED or TD group. Eligible participants will be scheduled to speak with a study clinician via phone or secure Zoom call to obtain informed consent prior to completing further screening and baseline study procedures.
Written informed consent will be obtained from subjects' parent/guardian prior to initiation of the study protocol. Subjects aged 7 and older will sign age-appropriate assent forms. The study subjects and their parent may take as much time as they feel necessary to consider their participation in the study as well as consult with their family members or physician. Subjects may remain on most current treatments while participating in this study. Participation in this study is voluntary, and subjects may withdraw from the study at any time.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •- Emotional Dysregulation Group
- •Male or female subjects, 6-12 years of age.
- •Current symptoms of emotional dysregulation as indicated by combined T-scores on the Child Behavior Checklist > 180 on the Anxiety/Depression + Aggression + Attention subscales.
- •Score 15 or above on the clinician YMRS
- •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 representative 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.
- •Subject must have access to a computer with a camera, speaker, microphone, and internet connection.
- •Subject must be willing to refrain from treatment changes during the study protocol.
- •Typically Developing Control Group
- •Age-, sex-matched with ED participants.
- •No significant traits of ED as screened by parent and clinician YMRS both under scores of 6
- •No previous psychiatric history as confirmed by clinician interview
- •No significant psychopathology as screened on the CBCL (Subdomain T-scores <60).
- •Participant weight is above the 5th percentile and below the 95th percentile, per CDC child BMI categories (https://www.cdc.gov/obesity/basics/childhood-defining.html)
排除标准
- •Investigator and his/her immediate family (defined as the investigator's spouse, parent, child, grandparent, or grandchild).
- •Serious or unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
- •History of bleeding diathesis, including those with von Willebrand 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.
- •DSM-IV substance use, abuse, or dependence
- •Any concomitant medication with primary central nervous system activity other than specified in the Concomitant Medication portion of the protocol.
- •Current diagnosis of schizophrenia or psychosis.
- •Females who have started menstruating.
- •Pregnant or nursing.
- •Judged to clinically be at serious suicidal risk or C-SSRS score ≥
- •History of intellectual disability as reported by parent
研究组 & 干预措施
Placebo
Participants in the placebo arm will receive placebo (no active ingredients) in effervescent tablet form daily for 8 weeks. Participants will undergo neuroimaging before and after the 8-week treatment phase.
干预措施: Placebo (Drug)
Control Group
Typically-developing controls will undergo neuroimaging twice (8 weeks apart) and will receive no intervention during the 8-week window.
N-Acetylcysteine (also known as NAC)
Participants in the NAC arm will receive NAC in effervescent tablet form daily for 8 weeks . Participants will undergo neuroimaging before and after the 8-week treatment phase.
Interventions:
Drug: N-Acetylcysteine (NAC)
干预措施: N-Acetyl Cysteine (NAC) (Drug)
结局指标
主要结局
Mean Change in the Clinician-Young Mania Rating Scale (C-YMRS) Score
时间窗: Baseline to Endpoint (Week 8)
The YMRS consists of 11 items rated on a scale from 0 (symptoms not present) to 4 (symptoms extremely severe). It is used to assess manic symptoms. Scores from each item are summed to obtain the total YMRS score. The YMRS score ranges from 0-60. A higher score means a higher manic state. Questions are asked about the last week. This scale is generally accepted as the main outcome measure in studies of pediatric bipolar disorder and is linked directly to the core symptoms of mania.
Mean Change in the Clinical Global Impression (CGI) scale for mania, depression, and bipolar disorder.
时间窗: Baseline to Endpoint (Week 8)
The CGI is a measure of illness severity adapted for specific disorders. It allows rating of mania, depression, and overall bipolar disorder illness, as well as other conditions frequently comorbid with bipolar disorder. The severity score ranges from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The improvement score ranges from 1 (very much improved) to 7 (very much worse). Collected at the baseline visit, weeks 2, 4 and 6, and at endpoint as an accepted measure of clinician rated improvement to assess the impact of treatment on bipolar disorder and other comorbid conditions.
Change from baseline to endpoint in the clinician measure Children's Depression Rating Scale (CDRS)
时间窗: Baseline to Endpoint (Week 8)
The CDRS (Poznanski, Freeman et al. 1985) is modeled after the Hamilton Depression Rating Scale for adults, but includes questions relevant to youth, such as questions about school, family and peer functioning. This 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. This scale is generally accepted as the main outcome in studies assessing childhood depression and is linked directly to the core symptoms of depression. Collected at baseline visit, weeks 2, 4 and 6, and at endpoint.
次要结局
- Mean Change in Child Behavior Checklist (CBCL) scores(Baseline to Endpoint (Week 8))
- Mean Change in Social Responsiveness Scale (SRS) Scores(Baseline to Endpoint (Week 8))
- Mean Change in the Parent-Young Mania Rating Scale (P-YMRS) Score(Baseline to Endpoint (Week 8))
- Mean Change in the Children's Depression Rating Scale-Parent (CDRS-P) Score(Baseline to Endpoint (Week 8))
- Mean Change in the Modified Overt Aggression Scale (MOAS)- Parent(Baseline to Endpoint (Week 8))
研究者
Janet Wozniak, MD
Associate Professor
Massachusetts General Hospital