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Functional Connectivity Alterations in Suicidal Patients Among Opioid Users

Primary Purpose

Substance Abuse, Suicide, Depression

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Repetitive Transcranial Magnetic Stimulation (rTMS)

sham rTMS

About this trial

This is an interventional treatment trial for Substance Abuse

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

The Menninger ClinicRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Active rTMS

Sham rTMS

Arm Description

10 sessions of active rTMS

10 sessions of sham rTMS

Outcomes

Primary Outcome Measures

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

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

Active vs sham rTMS

Secondary Outcome Measures

Full Information

NCT ID

NCT05489042

First Posted

June 27, 2022

Last Updated

March 28, 2023

Sponsor

Baylor College of Medicine

Collaborators

American Foundation for Suicide Prevention, National Institute on Drug Abuse (NIDA)

1. Study Identification

Unique Protocol Identification Number

NCT05489042

Brief Title

Functional Connectivity Alterations in Suicidal Patients Among Opioid Users

Official Title

Functional Connectivity Alterations in Suicidal Patients Among Opioid Users

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

January 4, 2022 (Actual)

Primary Completion Date

January 4, 2025 (Anticipated)

Study Completion Date

January 4, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Baylor College of Medicine

Collaborators

American Foundation for Suicide Prevention, National Institute on Drug Abuse (NIDA)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Substance Abuse, Suicide, Depression

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

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

Participant

Masking Description

The participant will not be aware of if they are receiving TMS treatment or sham TMS treatment.

Allocation

Randomized

Enrollment

80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Active rTMS

Arm Type

Experimental

Arm Description

10 sessions of active rTMS

Arm Title

Sham rTMS

Arm Type

Sham Comparator

Arm Description

10 sessions of sham rTMS

Intervention Type

Device

Intervention Name(s)

Repetitive Transcranial Magnetic Stimulation (rTMS)

Intervention Description

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

Intervention Type

Device

Intervention Name(s)

sham rTMS

Intervention Description

10 sessions of sham rTMS

Primary Outcome Measure Information:

Title

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

Description

Changes in functional connectivity between opioid users and healthy subjects

Time Frame

1 day

Title

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

Description

Active vs sham rTMS

Time Frame

12 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility 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)

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Hyuntaek Oh, PhD

Phone

713-275-5019

hoh@menninger.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Julia Myerson

Phone

713-275-5228

jmyerson@menninger.edu

Facility Information:

Facility Name

The Menninger Clinic

City

Houston

State/Province

Texas

ZIP/Postal Code

77035

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Hyuntaek Oh, PhD

Phone

713-275-5019

hoh@menninger.edu

12. IPD Sharing Statement

Plan to Share IPD

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Functional Connectivity Alterations in Suicidal Patients Among Opioid Users

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