Neurobiology of Treatment Responses in MDD

Neurobiology of Non-Specific and Specific Treatment Responses in Major Depression

The primary study intent is to examine biological mechanisms associated with acute and chronic treatment responses in major depressive disorder (MDD). It is hypothesized that treatment responsiveness, representing endogenous opioid system function, will be associated with acute improvements in mood state over a 10-week treatment trial in MDD. Potential (bio) markers of treatment effects will be tested against psychophysical responses to placebo and active treatments.

Study Overview

• Status: Withdrawn
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: Duloxetine; Drug: Placebo

Detailed Description

Volunteers will be randomized to receive placebo pills or a commercially available SNRI for 10 weeks. Volunteers will undergo imaging with structural and functional MRI and PET with [11C]carfentanil to determine baseline μOR BPND and changes in BPND measures during acute i.v. medication administration at the time of scanning before and after the 10-week treatment period.

To elicit the activation of µ-opioid-mediated neurotransmission in the scanner, we utilize the introduction of medication (active or inactive) 1mL into an intravenous port every 4 minutes, 15 sec per infusion, starting 45 minutes after radiotracer administration, until scan completion. Participants are made aware that the study drug will be administered at the time a computer-generated human voice recording reads a second-by-second count of the infusion timing (15 sec).

• Study Type: Interventional
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Chandni Sheth, PhD; Phone Number: 8015871622; Email: Chandni.sheth@utah.edu
• Study Contact Backup: Name: Allison Bustamante; Phone Number: 8017421517; Email: utahneuroimagelab@gmail.com

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • University of Utah
      • Contact: Chandni Sheth, PhD; Phone Number: 801-587-1622; Email: chandni.sheth@utah.edu
      • Contact: Allison Bustamante; Phone Number: 8017421517; Email: utahneuroimagelab@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Meet DSM V criteria for Major Depressive Episode, single episode or recurrent, for at least a month;
• Unmedicated for at least 10 half-lives of the previous AD used;
• Willing to limit the introduction of any new treatments during the study;
• 18 - 55 years of age;
• Right handed;
• Capable of giving written informed consent;
• Hamilton Depression Rating Scale (17-item HDRS, not including atypical features) >15 at screening and randomization;

Exclusion Criteria:

• Major medical illness (e.g., cancer, HIV, Hepatitis C, etc.) or concurrent, untreated, or symptomatic medical illnesses, including acute or ongoing pain, autoimmune or inflammatory disease;
• Use of narcotic analgesics within the last 6 months or regular use of sleeping aids (including benzodiazepines and related compounds), more than twice a week;
• Recent history of substance abuse (within the last 6 months) or history of substance dependence (lifetime);
• Other comorbid psychiatric illnesses, such as Bipolar Disorder, Obsessive Compulsive Disorder, Panic Disorder, any psychosis, or Axis II diagnoses. Generalized Anxiety and Social Anxiety Disorders will NOT be considered exclusionary given their common association with MDD
• Concurrent participation in other therapeutic trials;
• Pregnancy/nursing;
• Ongoing treatment with medications with psychotropic properties;
• Contraindications to PET or MRI methods;
• Impairments, activities or situations that would prevent completion of the study protocol;
• Prior non-response to duloxetine;
• Active suicidal ideation.
• Urine screens positive for opioids or any substances of abuse.
• Allergy to fentanyl (because of structural similarity to the radiotracer [11C]carfentanil to be employed in the study).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional; 10 weeks of duloxetine beginning at 30 mg per day for week 1, then 60 mg / day thereafter.	Drug: Duloxetine; 10 week treatment; Other Names: Cymbalta
Placebo Comparator: Placebo; 10 weeks of placebo once daily for 1 week, then twice daily therafter.	Drug: Placebo; 10 week treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mu-opioid receptor binding capacity	derived from PET scans	10 weeks
depression score	HRSD-17 score	10 weeks

Collaborators and Investigators

• Sponsor: University of Utah

Study record dates

Study Major Dates

• Study Start (Anticipated): November 1, 2021
• Primary Completion (Anticipated): May 1, 2023
• Study Completion (Anticipated): May 1, 2023

Study Registration Dates

• First Submitted: February 24, 2017
• First Submitted That Met QC Criteria: February 24, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): April 24, 2023
• Last Update Submitted That Met QC Criteria: April 20, 2023
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Antidepressive Agents; Dopamine Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Duloxetine Hydrochloride
• Other Study ID Numbers: 00095062

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