Study of Naltrexone-Induced Blockade of Antidepressant Effects

NCT04322526 | Completed Phase 4 Results FDA Drug

• 1 other identifier: PRO16050133
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to determine whether antidepressant placebo effects and contextual cues broadly, can be blocked by one single dose of the µ-opioid antagonist naltrexone. To test this hypothesis, un-medicated, patients with MDD completed a randomized, double-blind, placebo-controlled, cross-over study of 50mg of the µ-opioid antagonist naltrexone or matching placebo, immediately before a Pharmaco-fMRI scanning session.

Conditions

Depression; Major Depressive Disorder

Outcome Measures

Primary Outcomes (2)

• BOLD Responses in the rACC Cortex During the Processing of Contextual Cues at Baseline (Post-placebo)

  In order to identify the neural correlates of contextual processing, we examined changes in blood oxygenation level-dependent (BOLD) signal during the post-placebo fMRI scanning session.

  [Approximately at day 1, 7]

• Naltrexone-induced Changes in BOLD Responses in the rACC Cortex During the Processing of Contextual Cues (Placebo vs. Naltrexone)

  In order to identify naltrexone-induced changes in the neural correlates of contextual processing, we examined changes in blood oxygenation level-dependent (BOLD) during the fMRI scanning session between Naltrexone vs. placebo pill.

  [Approximately at day 1, 7]

Study Arms (2)

Naltrexone, then placebo

EXPERIMENTAL

Naltrexone is thought to strongly block μ-opioid receptors. Oral (pill) opioid antagonist which will be used to modulate neural responses during the Contextual Framing and the Antidepressant fMRI Task.

Drug: Naltrexone 50 Mg Oral Tablet; Drug: Placebo oral tablet

Placebo, then naltrexone

PLACEBO COMPARATOR

In the naltrexone condition, participants will receive one tablet of 50mg Naltrexone hydrochloride.

Drug: Naltrexone 50 Mg Oral Tablet; Drug: Placebo oral tablet

Interventions

Naltrexone 50 Mg Oral Tablet DRUG

Naltrexone hydrochloride (ReVia®. Toronto, ON: Teva Canada Limited; 2015) (onset of action: ≥15 minutes; peak effect: \~1 hour; duration: \~24 hours).

Naltrexone, then placebo; Placebo, then naltrexone

Placebo oral tablet DRUG

Placebo tablet that has no inherent power to produce an effect. In the inert pill condition, participants will receive an oral placebo tablet.

Naltrexone, then placebo; Placebo, then naltrexone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Adults, age 18-55 years; fluent in English and with the capacity to understand the nature of the study and sign the written informed consent since the research instruments used in this study are not available in other languages;
• Written informed consent obtained;
• Outpatients with a current primary diagnosis of nonpsychotic Major Depressive Disorder (MDD) per the Mini-International Neuropsychiatric Interview (M.I.N.I) with or without certain anxiety disorders (e.g., generalized anxiety, panic, agoraphobia, social phobia, and specific phobia); HDRS-17 score of ≥ 16 at Screening Visit;
• No more than one failed antidepressant trial of adequate dose and duration, as defined by the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (MGH-ATRQ);
• Participants will need to be antidepressant medication-free for at least 21 days prior to the collection of imaging data (five weeks for fluoxetine). However, individuals currently taking antidepressants will not be eligible to enroll in the study, even if they are willing to stop their medications.

You may not qualify if:

• Currently taking opioid analgesics or in acute opioid withdraw.
• Pregnant or breastfeeding or plan to become pregnant over the duration of the study;
• History (lifetime) of psychotic depressive, schizophrenic, bipolar (I, II, or NOS), schizoaffective, or other Axis I psychotic disorders;
• Meeting M.I.N.I. criteria for substance dependence in the last 6 months, except for nicotine, or substance abuse in the last 2 months;
• Requiring immediate hospitalization for psychiatric disorder or have an unstable general medical condition (GMC) that will likely require hospitalization or to be deemed terminal (life expectancy \< 6 months after study entry);
• Requiring medications for their GMCs that contraindicate treatment with naltrexone;
• Having epilepsy or other conditions requiring an anticonvulsant;
• Receiving or have received during the current episode vagus nerve stimulation, ECT, or rTMS.
• Currently taking any psychiatric medication or other potential augmenting agents (e.g., T3 in the absence of thyroid disease, lithium, buspirone); Taking thyroid medication for hypothyroidism may be included only if they have been stable on the thyroid medication for 3 months;
• Receiving therapy that is depression specific, such as CBT or Interpersonal Psychotherapy of Depression (participants can participate if they are receiving psychotherapy that is not targeting the symptoms of depression, such as supportive therapy, marital therapy);
• Currently actively suicidal or considered a high suicide risk;
• Currently enrolled in another study, and participation in that study contraindicates participation in this study;
• Any reason not listed herein yet, determined by the site PI and research staff that makes participation in the study hazardous.
• Having any contraindication for the performance of an MRI, such as: the presence of metal implants or foreign metallic objects (e.g., braces or extensive dental work), severe claustrophobia, or inability to tolerate the scanning procedures.

Sponsors & Collaborators

• Marta Peciña, MD PhD: lead
• Brain & Behavior Research Foundation: collaborator

Study Sites (1)

Bellefield Towers

Pittsburgh, Pennsylvania, 15213, United States

Location

Related Publications (1)

• Chen J, Mizuno A, Lyew T, Karim HT, Karp JF, Dombrovski AY, Pecina M. Naltrexone modulates contextual processing in depression. Neuropsychopharmacology. 2020 Nov;45(12):2070-2078. doi: 10.1038/s41386-020-00809-2. Epub 2020 Aug 25.

  PMID: 32843703 DERIVED

MeSH Terms

Conditions

Depression; Depressive Disorder, Major

Interventions

Naltrexone; Tablets

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Limitations and Caveats

This study does not have a healthy control condition, and therefore, results cannot be generalized beyond depression.

Results Point of Contact

• Title: Dr. Marta Pecina
• Organization: University of Pittsburgh

pecinam@upmc.edu

734-945-2473

Study Officials

• Marta Peciña, MD, PhD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double-blinded
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor

Model Details: This is a pharmaco-fMRI study of one single dose of naltrexone or placebo followed by an fMRI session in a crossover design.

Study Record Dates

• First Submitted: March 23, 2020
• First Posted: March 26, 2020
• Study Start: July 1, 2017
• Primary Completion: July 15, 2018
• Study Completion: July 15, 2018
• Last Updated: April 21, 2020
• Results First Posted: April 21, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Immediately following publication upon request. No end date.
• Access Criteria: Anyone who wishes to access the data.

Locations

US (1)