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

Primary Purpose

Depression

Status

Unknown status

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

N-acetyl cysteine

About this trial

This is an interventional treatment trial for Depression

Eligibility Criteria

15 Years - 24 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion:

Male or female subjects 15 years, 0 months - 24 years, 11 months of age at screening
For minor, at least one parent or step-parent/guardian with whom the subject lives is willing to participate in research sessions
For minor, the child and relative(s) are able and willing to give written informed assent/consent to participate, respectively
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)
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:

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
Patient has a DSM-5 diagnosis of autism, pervasive developmental disorder, OCD, PTSD, or Tourette's disorder
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
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
Patient has history of major neurological disorders (such as epilepsy), or head trauma with > 10 minutes loss of consciousness
Patient has evidence of mental retardation (IQ less than 70), as determined by the Wechsler Abbreviated Scale of Intelligence (WASI)
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
Patient has history of allergic reaction to N-acetylcysteine

Sites / Locations

University of Cincinnati, Department of Psychiatry & Behavioral NeuroscienceRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

N-acetyl cysteine

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Young Mania Rating Scale (YMRS) scores

A secondary outcome will be change in manic symptom, measured by YMRS scores, from baseline to endpoint.

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.

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.

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.

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.

Full Information

NCT ID

NCT02865629

First Posted

June 28, 2016

Last Updated

May 7, 2018

Sponsor

University of Cincinnati

1. Study Identification

Unique Protocol Identification Number

NCT02865629

Brief Title

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

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Unknown status

Study Start Date

August 2016 (undefined)

Primary Completion Date

August 2019 (Anticipated)

Study Completion Date

September 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Cincinnati

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Depression

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

22 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

N-acetyl cysteine

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

N-acetyl cysteine

Other Intervention Name(s)

Acetylcysteine

Intervention Description

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).

Primary Outcome Measure Information:

Title

Hamilton Depression Rating Scale (HAM-D) scores

Description

The primary outcome will be change in depressive symptoms, as measured by HAMD scores, from baseline to endpoint.

Time Frame

Baseline to endpoint (8 weeks)

Secondary Outcome Measure Information:

Title

Young Mania Rating Scale (YMRS) scores

Description

A secondary outcome will be change in manic symptom, measured by YMRS scores, from baseline to endpoint.

Time Frame

Baseline to endpoint (8 weeks)

Title

Hamilton Anxiety Rating Scale (HAM-A) scores to measure anxiety symptoms

Description

A secondary outcome will be change anxiety symptoms, as measured by HAM-A scores, from baseline to endpoint.

Time Frame

Baseline to endpoint (8 weeks)

Title

Clinical Global Impression of Severity (CGI-S) scores

Description

A secondary outcome will be change in subjects' overall clinical condition, as measured by CGI-S scores, from baseline to endpoint.

Time Frame

Baseline to endpoint (8 weeks)

Title

Connectivity index, as defined by the temporal bivariate correlation between fMRI signal fluctuations in the left ventrolateral prefrontal cortex and the left striatum

Description

Time Frame

Baseline to endpoint (8 weeks)

Title

Correlation between change in depressive symptoms and change in connectivity index

Description

Time Frame

Baseline to endpoint (8 weeks)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

15 Years

Maximum Age & Unit of Time

24 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion: Male or female subjects 15 years, 0 months - 24 years, 11 months of age at screening For minor, at least one parent or step-parent/guardian with whom the subject lives is willing to participate in research sessions For minor, the child and relative(s) are able and willing to give written informed assent/consent to participate, respectively 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) 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: 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 Patient has a DSM-5 diagnosis of autism, pervasive developmental disorder, OCD, PTSD, or Tourette's disorder 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 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 Patient has history of major neurological disorders (such as epilepsy), or head trauma with > 10 minutes loss of consciousness Patient has evidence of mental retardation (IQ less than 70), as determined by the Wechsler Abbreviated Scale of Intelligence (WASI) 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 Patient has history of allergic reaction to N-acetylcysteine

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fabiano G. Nery, MD, PhD

Phone

513.558.5035

neryfo@email.uc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Fabiano G. Nery, MD, PhD

Organizational Affiliation

University of Cincinnati

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Cincinnati, Department of Psychiatry & Behavioral Neuroscience

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45219

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Stephanie Schaeper, B.S.

Phone

513-558-5953

schaepsi@ucmail.uc.edu

First Name & Middle Initial & Last Name & Degree

Fabiano Nery, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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