NCT05046184

Elucidating the Neurocircuitry of Irritability With High-Field Neuroimaging to Identify Novel Therapeutic Targets

Elucidating the Neurocircuitry of Irritability With High-Field Neuroimaging to Identify Novel

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 165 (actual)
• Sponsor: University of Texas Southwestern Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The study is investigating dysfunctions in neurocircuitry in regards to irritability with healthy controls (HC) and individuals with Major Depressive Disorder (MDD) by performing MRIs. The MDD group will also be randomized to receive ketamine or midazolam to investigate changes post-treatment in neurocircuitry with regards to irritability.

Detailed description

The proposed study aims to 1 (Aim 1) identify dysfunctions in neurocircuitry that engender irritability, and (Aim 2) determine how changes in neurocircuit function related to change in irritability. We will accomplish Aim 1 with resting-state and frustrative nonreward (FNR) task-based fMRI data from n=30 HCs and n=60 subjects with MDD ((Fig 3). For Aim 2, we will randomize the MDD cohort (n=60; same as Aim 1) to 2 weeks of twice-weekly 40-minutes long intravenous infusion of either ketamine (0.5 mg/kg) or midazolam (0.02 mg/kg) in a double-blind parallel-arm fashion, and by repeating clinical assessments and fMRI scans after the last infusion. The central hypothesis of the proposed study is that striatum is a key hub in the neurocircuitry of irritability, and that treatment-related improvement in irritability is associated with normalization of these neurocircuit functioning.

Conditions

• Major Depressive Disorder
• Healthy Controls

Interventions

Type	Name	Description
DRUG	Ketamine Hydrochloride	Subjects with MDD will receive 2 weeks of twice-weekly 40-minutes long IV infusion of ketamine (0.5 mg/kg). Ketamine will be dissolved in 0.9% saline in a total volume of 100 mL and administered with an infusion pump at a constant rate.
DRUG	Midazolam injection	Subjects with MDD will receive 2 weeks of twice-weekly 40-minutes long IV infusion of midazolam (0.02 mg/kg). Midazolam will be dissolved in 0.9% saline in a total volume of 100 mL and administered with an infusion pump at a constant rate.

Timeline

• Start date: 2022-05-05
• Primary completion: 2025-04-30
• Completion: 2025-04-30
• First posted: 2021-09-16
• Last updated: 2025-05-08

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study