## Protocol Section
### Identification Module
**NCT ID:** NCT01237379

**Brief Title:** Peroxisomal Defects and Familial Risk for Bipolar Disorder

**Official Title:** Peroxisomal Defects and Familial Risk for Bipolar Disorder

#### Organization Study ID Info
**ID:** McNamara NARSAD
#### Organization
**Class:** OTHER
**Full Name:** University of Cincinnati
### Status Module
#### Completion Date
**Date:** 2013-10

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2014-12-23

**Type:** ESTIMATED

**Last Update Submit Date:** 2014-12-19

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2013-10

**Type:** ACTUAL

#### Start Date
**Date:** 2010-10

**Status Verified Date:** 2014-12

#### Study First Post Date
**Date:** 2010-11-09
**Type:** ESTIMATED
**Study First Submit Date:** 2010-10-21
**Study First Submit QC Date:** 2010-11-05
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** National Alliance for Research on Schizophrenia and Depression

#### Lead Sponsor

**Class:** OTHER

**Name:** University of Cincinnati

#### Responsible Party

**Investigator Affiliation:** University of Cincinnati

**Investigator Full Name:** Robert McNamara

**Investigator Title:** Associate Professor

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** False

### Description Module

**Brief Summary:** The purpose of this study is to screen for peroxisome defects in child and adolescent offspring of Bipolar Disorder I (BD-I) parents at different stages of risk for transitioning to mania and following the onset of mania.

Prediction 1: Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls.

Prediction 2: Indices of peroxisomal function will be correlated with Red Blood Cells Docosahexaenoic acid (DHA) composition.

Prediction 3: Graded deficits in measures of peroxisomal function will be inversely correlated with manic and depression symptom severity scores.

**Detailed Description:** Overall Study Design: This study entails collecting fasting venous blood (20 ml) from, and administering the 'omega-3 questionnaire' to, subjects being recruited from ongoing National Institute of Mental Health (NIMH)-sponsored trials within the Department of Psychiatry, University of Cincinnati College of Medicine. Specifically, blood will be collected from 20 healthy controls (i.e., no personal or family history of any Axis I mood disorder according to the Diagnostic and Statistical Manual of Mental Disorders-IV \[DSM-IV\]) and 20 asymptomatic high-risk (i.e., have a biological parent with BD-I) adolescents (aged 10-18 years old) recruited for study MH077138 (UC-IRB #: 07-04-10-03, BITREC Project 3; PI: DelBello), 20 ultra-high risk (i.e., have a biological parent with BD-I and a Major Depressive Disorder (MDD) diagnosis) recruited for study MH083924 (UC-IRB #: 04-09-15-03, CO-Principal Investigators DelBello/McNamara), and 20 adolescents who are admitted for their first hospitalization and who have a diagnosis of BD-I recruited for study MH080973 (UC-IRB #: 08-10-30-01, Principal Investigator: DelBello). Blood will then be processed, and de-identified tubes sent to the Kennedy Krieger Institute, Peroxisomal Diseases Section, to determine the following measures of peroxisomal function: (1) plasma very long chain fatty acids (C24:0 \& C26:0) concentrations, (2) plasma bile acid C27 intermediate (dehydrocrepenynic acid {DHCA},tetrahydrocannabinolic acid {THCA})concentrations, (3) plasma pipecolic acid concentrations, and (4) Red Blood Cell (RBC) plasmalogen concentrations. Additionally, RBC fatty acid composition will be determined by gas chromatography, and platelet function and plasma inflammatory markers assayed using commercially available kits according to manufacturer's instructions.

### Conditions Module

**Conditions:**

- Bipolar Disorder

- Mania

### Design Module

#### Bio Spec

**Description:** Laboratory methods: The gas chromatography procedure used to determine red blood cell fatty acid composition. Briefly, total fatty acid composition will be determined. Indices of peroxisome function, including (1) plasma very long chain fatty acids concentrations, (2) plasma bile acid C27 intermediate concentrations, (3) plasma pipecolic acid concentrations, and (4) RBC plasmalogen concentrations, will be determined by liquid chromatography tandem mass spectrometry and gas chromatography. Plasma cytokine and C-Reactive Protein (CRP)concentrations will be determined. All blood analyses will be performed by a technician blinded to diagnostic group identity.

**Retention:** NONE_RETAINED

#### Design Info

**Observational Model:** CASE_CROSSOVER

**Time Perspective:** RETROSPECTIVE

#### Enrollment Info

**Count:** 80

**Type:** ACTUAL

**Study Type:** OBSERVATIONAL

### Arms Interventions Module

#### Arm Group 1

**Label:** Health Controls

#### Arm Group 2

**Label:** Bipolar Patients with High-Risk of Mania

#### Arm Group 3

**Label:** Bipolar Patients with Ultra-High Risk

#### Arm Group 4

**Label:** First Manic Episode Bipolar Youth

### Outcomes Module

#### Primary Outcomes

**Description:** Prediction 1: Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls.

**Measure:** Youth with an elevated risk for developing BD-I and first-episode manic patients will exhibit graded deficits in measures of peroxisomal function compared with healthy controls.

**Time Frame:** 1 day

#### Secondary Outcomes

**Description:** Prediction 3: Graded deficits in measures of peroxisomal function will be inversely correlated with manic and depression symptom severity scores.

**Measure:** peroxisomal function will be inversely correlated with manic and depression symptom severity scores.

**Time Frame:** 1 day

**Description:** Prediction 2: Indices of peroxisomal function will be correlated with RBC DHA composition.

**Measure:** Indices of peroxisomal function will be correlated with RBC DHA composition.

**Time Frame:** 1 day

### Eligibility Module

**Eligibility Criteria:** Subject characteristics: All subjects will be 10-18 year old males and females. Up to 80 patients will be enrolled in this study. Subjects will be screened according to previously approved individual study criteria (UC-IRB #: 07-04-10-03; 04-09-15-03; 08-10-30-01).

Inclusion Criteria:

* 10 -18 year old males \& females
* Based on currently enrolled study.

Exclusion Criteria:

* Based on currently enrolled study.

**Healthy Volunteers:** True

**Maximum Age:** 18 Years

**Minimum Age:** 10 Years

**Sampling Method:** PROBABILITY_SAMPLE

**Sex:** ALL

**Standard Ages:**

- CHILD

- ADULT

**Study Population:** Subjects: In order to accomplish this aim, 20 healthy controls, 20 high-risk, 20 ultra-high risk, and 20 first-episode manic youth (ages 10-18 years old) will be recruited at a rate of 1 subject/group per month over the first 20 months. Subjects being recruited from the following IRB approved NIMH-sponsored trials: MH077138 (UC-IRB #: 07-04-10-03, BITREC Project 3; PI: DelBello), MH083924 (UC-IRB #: 04-09-15-03, CO-PIs DelBello/McNamara), and MH080973 (UC-IRB #: 08-10-30-01, PI: DelBello).

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Cincinnati

**Country:** United States

**Facility:** University of Cincinnati

**State:** Ohio

**Zip:** 45219

#### Overall Officials

**Official 1:**

**Affiliation:** University of Cincinnati

**Name:** Robert McNamara, PhD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000068105

- Term: Bipolar and Related Disorders

- ID: D000019964

- Term: Mood Disorders

- ID: D000001523

- Term: Mental Disorders

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: BXM

- Name: Behaviors and Mental Disorders

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M2598

- Name: Mania

- Relevance: LOW

- As Found: Unknown

- ID: M4996

- Name: Bipolar Disorder

- Relevance: HIGH

- As Found: Bipolar Disorder

- ID: M226

- Name: Bipolar and Related Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M21835

- Name: Mood Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M4815

- Name: Mental Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M14473

- Name: Psychotic Disorders

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000001714

- Term: Bipolar Disorder

### Misc Info Module

- Version Holder: 2024-05-24
