Evaluating the Role of the Microbiome in Antidepressant Treatment in Adolescents.

The goal of this observational study is to learn about the role of the human gut microbiome in antidepressant treatment response in adolescents with Major Depressive Disorder (MDD). Specifically, the study aims to collect microbiota samples of adolescents treated with fluoxetine, over the span of 8-weeks, to:

• determine the influence of the microbiome on the efficacy of fluoxetine to treat adolescent depression.
• test whether the gut microbiome from different timepoints can predict ultimate success of fluoxetine
• investigate the interaction of gut microbiome composition and pharmacogenetic metabolizer status on steady-state plasma concentrations of fluoxetine.

Depression symptom severity will be evaluated upon enrollment and 6-weeks into antidepressant treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression in Adolescence

Detailed Description

For this project the investigators are interested in changes in the gut microbiome associated with adolescent depression and the influence of the microbiome on the efficacy of fluoxetine to treat adolescent depression. It is hypothesized that the composition of the human gut microbiome alters the response to fluoxetine of adolescents with depression. This study aims to collect gut microbiota of adolescents being treated with antidepressants at several timepoints to (1) determine the efficacy of fluoxetine to treat depression, (2) test whether the gut microbiome from different timepoints can predict ultimate success of fluoxetine, and (3) investigate the interaction of gut microbiome composition and pharmacogenetic metabolizer status on steady-state plasma concentrations of fluoxetine. Adolescent patients with clinically significant depressive symptoms who are prescribed fluoxetine, from Rady Children's Hospital San Diego (RCHSD) Inpatient Child and Adolescent Psychiatry Services (CAPS), will be recruited for this study. Up to twelve stool samples are planned to be collected, including prior to start of antidepressant treatment for a baseline measure of gut microbiome composition, daily samples over during the first week of fluoxetine treatment, and then biweekly collections until the end of the 8-week study duration.

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Aaron Besterman, MD; Phone Number: 8589668145; Email: abesterman@rchsd.org
• Study Contact Backup: Name: Abbey Albertazzi, MA; Phone Number: 221939 8589661700; Email: aalbertazzi@rchsd.org

Study Locations

• United States
  • California
    • San Diego, California, United States, 92123
      • Rady Children's Hospital San Diego

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adolescents ages 13-17 with depression diagnosis

Description

Inclusion Criteria:

• Subjects from all ethnic backgrounds will be eligible to participate.
• Having clinically significant depressive symptoms based on a score >40 on the Children's Depression Rating Scale-Revised
• Prescribed more than 5mg of Fluoxetine (Prozac)
• Has an identifiable legal guardian.

Exclusion Criteria:

• Has been taking a standing psychotropic medication in the past 6 months
• Has been taking antibiotics or metformin during the past 6 months (known strong effects on gut microbiome)
• Admitted to RCHSD CAPS post-overdose (potential strong effects on gut microbiome)
• Currently using nicotine-containing substances (known strong effects on gut microbiome)

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiome composition	Gut microbiome composition will be characterized by analysis of stool samples	Stool samples will be collected at enrollment (baseline), then following enrollment: daily for the first 7 days and biweekly at weeks 2, 4, 6, and 8.
Efficacy of fluoxetine to treat depression symptoms in adolescents	Fluoxetine success will be characterized by change, from baseline to week 6 follow-up, of Children's Depression Rating Scale, Revised (CDRS-R) scores.	The CDRS-R will be administered at baseline and week 6.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of fluoxetine to improve self-reported depression symptoms in adolescents	Fluoxetine success will be characterized by the change, from baseline to week 6 follow-up, of self-reported depression symptom severity indicated by Mood and Feelings Questionnaire (MFQ) scores.	The MFQ will be administered at baseline and week 6.
Efficacy of fluoxetine to treat anxiety symptoms in adolescents	Fluoxetine success will be characterized by the change, from baseline to week 6 follow-up, of self-reported severity of recent anxiety symptoms indicated by the Screen for Child Anxiety Related Disorders (SCARED) scores.	The SCARED will be administered at baseline and week 6.
Pharmacogenetic (PGx) metabolizer status	Patients are divided into metabolic phenotype groups denoted as poor, intermediate, and ultrarapid metabolizers based on their specific variant profile of pharmacokinetic genes.	A saliva sample is collected for pharmacogenetic analysis at baseline
Steady-state plasma concentrations of fluoxetine	Steady-state plasma sample concentrations of fluoxetine and (active metabolite norfluoxetine).	Sample collected at week 6

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Rady Children's Hospital, San Diego
• Investigators: Principal Investigator: Rob Knight, PhD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): October 1, 2026

Study Registration Dates

• First Submitted: October 3, 2024
• First Submitted That Met QC Criteria: October 8, 2024
• First Posted (Actual): October 9, 2024

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Depression
• Other Study ID Numbers: 807323

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No