N-acetylcysteine in the Treatment of Depressive Symptoms in Bipolar Offspring

N-acetylcysteine in the Treatment of Depressive Symptoms in Youth at High-risk for Bipolar Disorder: a Functional Connectivity Study

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

Study Overview

• Status: Unknown
• Conditions: Depression
• Intervention / Treatment: Drug: N-acetyl cysteine

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.

• Study Type: Interventional
• Enrollment (Anticipated): 22
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabiano G. Nery, MD, PhD; Phone Number: 513.558.5035; Email: neryfo@email.uc.edu

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience
      • Contact: Stephanie Schaeper, B.S.; Phone Number: 513-558-5953; Email: schaepsi@ucmail.uc.edu
      • Principal Investigator: Fabiano Nery, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 24 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: N-acetyl cysteine; Following the screening and review of all laboratory studies, patients will be scheduled to receive N-acetylcysteine.

Drug: N-acetyl cysteine; N-acetylcysteine will be initiated at 600 mg PO daily for Week 1, then increased to 600 mg PO twice a day for Week 2, then increased to 600 mg PO morning and 1200 mg PO evening for Week 3, and then increased to 1200 mg PO twice a day for Week 4-8. Doses might be decreased anytime if clinically indicated. Following the study, all patients will be referred to treatment as usual. Adherence will be assessed in weekly visits in the first month and then bi-weekly in the second month. Adherence will be assessed by subject interview, pill counts during each study visit, and by legal guardian interview (if minor).; Other Names: Acetylcysteine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Rating Scale (HAM-D) scores	The primary outcome will be change in depressive symptoms, as measured by HAMD scores, from baseline to endpoint.	Baseline to endpoint (8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Young Mania Rating Scale (YMRS) scores	A secondary outcome will be change in manic symptom, measured by YMRS scores, from baseline to endpoint.	Baseline to endpoint (8 weeks)
Hamilton Anxiety Rating Scale (HAM-A) scores to measure anxiety symptoms	A secondary outcome will be change anxiety symptoms, as measured by HAM-A scores, from baseline to endpoint.	Baseline to endpoint (8 weeks)
Clinical Global Impression of Severity (CGI-S) scores	A secondary outcome will be change in subjects' overall clinical condition, as measured by CGI-S scores, from baseline to endpoint.	Baseline to endpoint (8 weeks)
Connectivity index, as defined by the temporal bivariate correlation between fMRI signal fluctuations in the left ventrolateral prefrontal cortex and the left striatum	A secondary outcome will be change in functional connectivity, as measured by the connectivity index, between the left ventrolateral prefrontal cortex and the left striatum from baseline to endpoint. The connectivity index is defined as the temporal bivariate correlation between fMRI signal fluctuations in the 2 regions of interest.	Baseline to endpoint (8 weeks)
Correlation between change in depressive symptoms and change in connectivity index	A secondary outcome will be correlation between changes in depressive symptoms and changes in functional connectivity, as measured by the connectivity index, between the left ventrolateral prefrontal cortex and left striatum from baseline to endpoint. The connectivity index is defined as the temporal bivariate correlations between fMRI signal fluctuations in the 2 regions of interest.	Baseline to endpoint (8 weeks)

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Investigators: Principal Investigator: Fabiano G. Nery, MD, PhD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (Anticipated): August 1, 2019
• Study Completion (Anticipated): September 1, 2019

Study Registration Dates

• First Submitted: June 28, 2016
• First Submitted That Met QC Criteria: August 9, 2016
• First Posted (Estimate): August 12, 2016

Study Record Updates

• Last Update Posted (Actual): May 14, 2018
• Last Update Submitted That Met QC Criteria: May 7, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Protective Agents; Respiratory System Agents; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: Nery UCNI NAC study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No