Don't get left behind! The modernized ClinicalTrials.gov is coming. Check it out now.
Say goodbye to ClinicalTrials.gov!
The new site is coming soon - go to the modernized ClinicalTrials.gov
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Functional Connectivity Alterations in Suicidal Patients Among Opioid Users

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05489042
Recruitment Status : Recruiting
First Posted : August 5, 2022
Last Update Posted : March 30, 2023
Sponsor:
Collaborators:
American Foundation for Suicide Prevention
National Institute on Drug Abuse (NIDA)
Information provided by (Responsible Party):
Hyuntaek Oh, PhD, Baylor College of Medicine

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Suicide is the 10th leading cause of death for Americans of all ages and more people in the United States now die from suicide than die from car accidents. Although death by firearm remains the most common cause of suicide in the United States, an intentional overdose of substance usage such as prescription opioids accounts for over 5,000 suicides per year. In 2017, more than 70,000 drug overdose deaths occurred, making it the leading cause of injury-related death, and well over half (67.8%) involved opioids. The dramatic increase in opioid overdose raises concerns about their contribution to suicidal outcomes (e.g., suicidal behavior, ideation, and attempts). Abuse of prescription opioids is characterized by the persistence of opioid use despite negative consequences. The neurobiology of opioid abuse involves the mesolimbic dopamine systems as the main neural substrate for opioid reward, and altered dopamine release in this system plays a role in opioid abuse. Moreover, the cortico-striatal system, especially the orbitofrontal cortex (OFC), has been associated with the abuse of many substances, including opioids and alcohol. Structural brain alterations in frontal areas, particularly the OFC, may cause executive control dysfunctions of mood which are highly associated with suicidal ideation. Recent preclinical work has shown that higher input from the OFC to the dorsal striatum (dSTR) is associated with compulsive reward-seeking behavior despite negative effects (e.g., punishment). In this study, the investigators propose that OFC/dSTR connectivity may be one neural differentiator that distinguishes between those who become compulsive users after initial opioid use and those that do not. Moreover, suicidal patients among those who become compulsive users may have higher OFC/dSTR connectivity compared to non-suicidal patients.

Condition or disease Intervention/treatment Phase
Substance Abuse Suicide Depression Device: Repetitive Transcranial Magnetic Stimulation (rTMS) Device: sham rTMS Not Applicable

Detailed Description:
The OFC is functionally connected to other cortical brain regions (e.g., prefrontal and parietal cortices) but also subcortical areas in the dorsal striatum, a core reward circuitry region. The functional connectivity between the OFC and the dorsal striatum also plays an important role in addiction, particularly opioid abuse, and suicide behaviors. Thus, it is clear that the investigators need a better understanding of the therapeutic mechanisms using non-invasive brain stimulation (e.g., TMS) treatment to the OFC as applied to opioid users. As such, the investigators propose to use a combination of interleaved TMS-fMRI, a novel method to observe and characterize causal manipulations of functional neural circuits, targeting the OFC and resting state functional magnetic resonance imaging (fMRI) to longitudinally study psychiatric symptoms (e.g., opioid craving, suicidal behaviors) changes in opioid users.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The administration of rTMS will adhere to a double-blinded, randomized, controlled design with 50% of the opioid users or opioid-related patients (e.g., suicidal or depressive patients) recruited to the study receiving placebo stimulation (sham) instead of active rTMS. The placebo stimulation will use a TMS coil of identical appearance that is designed to mimic the sensations associated with the active TMS coil.
Masking: Single (Participant)
Masking Description: The participant will not be aware of if they are receiving TMS treatment or sham TMS treatment.
Primary Purpose: Treatment
Official Title: Functional Connectivity Alterations in Suicidal Patients Among Opioid Users
Actual Study Start Date : January 4, 2022
Estimated Primary Completion Date : January 4, 2025
Estimated Study Completion Date : January 4, 2026

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Suicide

Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Active rTMS
10 sessions of active rTMS
 Device: Repetitive Transcranial Magnetic Stimulation (rTMS)
10 Sessions of rTMS - brief single pulse TMS or short TMS pulse bursts consisting of 2-5 pulses delivered per second at a standard intensity. If a brief single pulse TMS is applied, a standard single pulse TMS procedure will be used - This procedure consists of 10 trains of 180 seconds duration and each train will be separated by at least 30 seconds. If short TMS pulse bursts are applied, a standard theta-burst TMS procedure will be used - This procedure consists of TMS triplets (i.e., 3 pulses) that repeat for 10 trains of a total duration of 40-190 seconds and these bursts will be separated by at least 6 seconds and each train will be separated by at least 30 seconds
Sham Comparator: Sham rTMS
10 sessions of sham rTMS
 Device: sham rTMS
10 sessions of sham rTMS


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Functional Connectivity between the orbitofrontal cortex (OFC) and dorsal striatum in opioid users or opioid-related patients versus healthy subjects [ Time Frame: 1 day ]
    Changes in functional connectivity between opioid users and healthy subjects

  2. rTMS changes in dorsal striatum responses between those receiving active stimulation versus sham stimulation [ Time Frame: 12 days ]
    Active vs sham rTMS


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria Opioid Use Patients:

Each potential subject will be eligible for inclusion in this study only if the specific criteria listed below are met:

  • Be male or female aged 18-60 years old
  • Participation in H-22611;
  • Meets a World Health Organization Alcohol, Smoking and Substance Involvement Screening Test (WHO-ASSIST) score of 4+ in the opioid category;
  • Has depressive symptoms according to the Patient Health Questionnaire (PHQ)-9;
  • Has active suicidal thoughts according to Suicide Behaviors Questionnaire-Revised (SBQ-R);
  • Currently enrolled in The Menninger Clinic;
  • Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures;
  • Female subjects must be non-nursing and not pregnant at the times of fMRI experiments and rTMS treatment;
  • Has no contraindications to MRI (pacemaker, cochlear implants, metal in eyes, other metal implants, etc.); Meets the pre-screening magnetic resonance imaging (MRI) questions provided by the Center for Advanced MR Imaging (CAMRI);
  • Has no contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the coil, etc.).

Inclusion Criteria Healthy Controls:

Each potential subject will be eligible for inclusion in this study only if the specific criteria listed below are met:

  • Be male or female aged 18-60 years old;
  • No history of severe medical or neurological illnesses per history;
  • Be able to verbalize understanding of consent form, able to provide written informed consent, and verbalize willingness to complete study procedures;
  • Female subjects must be non-nursing and not pregnant at the time of fMRI experiments;
  • Has no contraindications to MRI (pacemaker, cochlear implants, metal in eyes, other metal implants, etc.): Meets the pre-screening MRI questions provided by the Center for Advanced MR Imaging (CAMRI);
  • Has no contraindications to TMS (any types of non-removable metal in their head except the mouth, or within 12 inches of the TMS coil, etc.).

Exclusion Criteria:

Any potential subject who meets any of the following criteria will be excluded from participating in the study if s/he has

  • In the opinion of the clinician and the research team at admission, be expected to fail to complete the study protocol due to probable relocation from The Menninger Clinic area or not tolerable to receive rTMS;
  • Unable to understand the design and requirements of the study;
  • Unable to sign informed consent for any reason;
  • Has an unstable medical condition, including Acquired immunodeficiency syndrome (AIDS), acute hepatitis, active TB, unstable cardiac disease, unstable diabetes, hepatic or renal insufficiency;
  • Female subjects who are pregnant or nursing;
  • Contraindications to MRI (pacemaker, cochlear implants, metal in the eye, other metal implants, etc.): Do not meet the pre-screening MRI questions provided by the CAMRI;
  • Contraindications to the noninvasive brain stimulation (NIBS) (any types of non- removable metal in their head except the mouth, or within 12 inches of the coil, etc.) Additional exclusion criteria for the TMS experiments are based on the recommendations described by the international consensus panel on brain stimulation;
  • Non-English speaking subjects (we do not have the staff and resources to include other languages)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05489042


Contacts
Layout table for location contacts
Contact: Hyuntaek Oh, PhD 713-275-5019 hoh@menninger.edu
Contact: Julia Myerson 713-275-5228 jmyerson@menninger.edu

Locations
Layout table for location information
United States, Texas
The Menninger Clinic Recruiting
Houston, Texas, United States, 77035
Contact: Hyuntaek Oh, PhD    713-275-5019    hoh@menninger.edu   
Sponsors and Collaborators
Baylor College of Medicine
American Foundation for Suicide Prevention
National Institute on Drug Abuse (NIDA)
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Layout table for additonal information
Responsible Party: Hyuntaek Oh, PhD, Assistant Professor, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT05489042    
Other Study ID Numbers: H-51048
1K25DA055156-01A1 ( U.S. NIH Grant/Contract )
YIG-1-141-20 ( Other Grant/Funding Number: AFSP )
First Posted: August 5, 2022    Key Record Dates
Last Update Posted: March 30, 2023
Last Verified: March 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
Layout table for MeSH terms
Substance-Related Disorders
Suicide
Behavioral Symptoms
 Self-Injurious Behavior
Chemically-Induced Disorders
Mental Disorders