Clinical trial NCT02865629: N-acetylcysteine in the Treatment of Depressive Symptoms in Bipolar Offspring
Official title: N-acetylcysteine in the Treatment of Depressive Symptoms in Youth at High-risk for Bipolar Disorder: a Functional Connectivity Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Depression
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
First posted: 2016-08-12
Enrollment: 22
Sex: ALL
Minimum age (years): 15
Maximum age (years): 24
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: N-acetylcysteine in the treatment of depressive symptoms in youth at high-risk for bipolar disorder: a functional connectivity study

Detailed description: To conduct an 8-week, open label study of N-acetylcysteine for the treatment of depressive symptoms in youth at high risk for bipolar disorder, with resting state functional magnetic resonance imaging (fMRI) examinations at baseline and endpoint. This proposal is innovative because it investigates the efficacy and tolerability of a novel pharmacological treatment in youth offspring of bipolar disorder, and examines the neurophysiology of predictors of mood disorders in youth at high risk for bipolar disorder. This study will obtain pilot data to propose a larger, neuroimaging-based, double-blind, placebo-controlled trial of N-acetylcysteine in youth at high risk for bipolar disorder. The expected outcome, that N-acetylcysteine will be efficacious in ameliorating depressive symptoms in youth at high risk for bipolar disorder, and that it will demonstrate improvement in functional connectivity within the left frontostriatal circuit associated with treatment response.

Eligibility criteria: Inclusion:

1. Male or female subjects 15 years, 0 months - 24 years, 11 months of age at screening
2. For minor, at least one parent or step-parent/guardian with whom the subject lives is willing to participate in research sessions
3. For minor, the child and relative(s) are able and willing to give written informed assent/consent to participate, respectively
4. Subject has at least one first degree relative with Bipolar I Disorder, as assessed by the Structured Clinical Interview for DSM (SCID) or the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-PL)
5. Subject shows evidence of current significant depressive symptoms as determined by a current Hamilton Depression Rating Scale (HAM-D) greater or equal to 8

Exclusion:

1. Patient has presence of current or lifetime history of manic or hypomanic mood episodes, psychotic disorders including schizophrenia, current major depressive episode, and/or more than two prior major depressive episodes
2. Patient has a DSM-5 diagnosis of autism, pervasive developmental disorder, OCD, PTSD, or Tourette's disorder
3. Patient has drug or alcohol abuse or dependence disorders in the three months prior to study recruitment, although a lifetime history of substance or alcohol disorders can be present if the patient has been abstinent for at least three months
4. Pregnancy; participants will be encouraged but not mandated to discuss a positive pregnancy test with their guardians (if minors) and we will follow local laws
5. Patient has history of major neurological disorders (such as epilepsy), or head trauma with \> 10 minutes loss of consciousness
6. Patient has evidence of mental retardation (IQ less than 70), as determined by the Wechsler Abbreviated Scale of Intelligence (WASI)
7. Patient has any contraindication for MRI, including metal in the body related to an injury or surgery (e.g., surgical clips, metal fragments in the eyes), piercings that cannot be removed, or braces
8. Patient has history of allergic reaction to N-acetylcysteine

Primary outcomes:
measure: Hamilton Depression Rating Scale (HAM-D) scores
timeFrame: Baseline to endpoint (8 weeks)
Secondary outcomes:
measure: Young Mania Rating Scale (YMRS) scores
timeFrame: Baseline to endpoint (8 weeks)
measure: Hamilton Anxiety Rating Scale (HAM-A) scores to measure anxiety symptoms
timeFrame: Baseline to endpoint (8 weeks)
measure: Clinical Global Impression of Severity (CGI-S) scores
timeFrame: Baseline to endpoint (8 weeks)
measure: Connectivity index, as defined by the temporal bivariate correlation between fMRI signal fluctuations in the left ventrolateral prefrontal cortex and the left striatum
timeFrame: Baseline to endpoint (8 weeks)
measure: Correlation between change in depressive symptoms and change in connectivity index
timeFrame: Baseline to endpoint (8 weeks)
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Fabiano G. Nery, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: