Functional Connectivity Alterations in Suicidal Patients Among Opioid Users

NCT05489042 | Recruiting DMC FDA Device

• 3 other identifiers: H-510481K25DA055156-01A1YIG-1-141-20
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Substance Abuse; Suicide; Depression

Outcome Measures

Primary Outcomes (2)

• Functional Connectivity between the orbitofrontal cortex (OFC) and dorsal striatum in opioid users or opioid-related patients versus healthy subjects

  Changes in functional connectivity between opioid users and healthy subjects

  1 day

• rTMS changes in dorsal striatum responses between those receiving active stimulation versus sham stimulation

  Active vs sham rTMS

  7 days

Study Arms (2)

Active rTMS

EXPERIMENTAL

5 sessions of active rTMS

Device: Repetitive Transcranial Magnetic Stimulation (rTMS)

Sham rTMS

SHAM COMPARATOR

5 sessions of sham rTMS

Device: sham rTMS

Interventions

Repetitive Transcranial Magnetic Stimulation (rTMS) DEVICE

5 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

Active rTMS

sham rTMS DEVICE

5 sessions of sham rTMS

Sham rTMS

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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);
• 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.).
• 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.).

You may not qualify if:

• 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 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;
• Non-English speaking subjects (we do not have the staff and resources to include other languages)

Sponsors & Collaborators

• Baylor College of Medicine: lead
• American Foundation for Suicide Prevention: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

The Menninger Clinic

Houston, Texas, 77035, United States

RECRUITING

Related Publications (13)

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• Oh H, Lee J, Gosnell SN, Patriquin M, Kosten T, Salas R. Orbitofrontal, dorsal striatum, and habenula functional connectivity in psychiatric patients with substance use problems. Addict Behav. 2020 Sep;108:106457. doi: 10.1016/j.addbeh.2020.106457. Epub 2020 Apr 27.

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MeSH Terms

Conditions

Substance-Related Disorders; Suicide; Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Mental Disorders; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Central Study Contacts

Hyuntaek Oh, PhD

CONTACT

713-275-5019; hoh@menninger.edu

Taylor Ly

CONTACT

713-275-5594; TLy1@menninger.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: The participant will not be aware of if they are receiving TMS treatment or sham TMS treatment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: 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.

Study Record Dates

• First Submitted: June 27, 2022
• First Posted: August 5, 2022
• Study Start: January 4, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: April 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)