Frontoparietal Synchronization to Modulate Drug Craving in Opioid Use Disorder

NCT03907644 | Completed

• 1 other identifier: 2019-001-00
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Opioid use disorder (OUD) is among the costliest and deadliest substance use disorders (SUDs) in the US and world-wide. Opioids were involved in 42,249 deaths in the US in 2016, which were more than deaths due to road accidents and gun violence combined. Opioid overdose deaths were five times higher in 2016 than 1999. Meanwhile, the treatment options for OUD are limited and long-term efficacy is poor. There is a hope that recent advances in understanding of the cognitive neuroscience underlying addictive behavior, like drug craving and its regulatory processes, can bring new opportunities for more effective and personalized treatment options for OUD. Drug craving is the signature aspect of OUD as well as other SUDs which has been associated with continued drug use and relapse. In previous studies, the investigators have shown significant response to drug related cues in both frontoparietal and limbic areas including amygdala and ventral striatum. In a recent pilot study, the investigators showed significant lower connectivity between amygdala and frontoparietal areas, including dorsolateral prefrontal cortex (DLPFC) and inferior parietal cortex (IPC), major nodes of the executive control network (ECN), in patients with OUD compared with healthy controls. The central role of the ECN is to perform top down regulation of subcortical limbic areas during self-control, emotion-regulation, and response- inhibition tasks. These processes are well known to be affected in different psychopathologies including SUDs. There is a growing body of evidence that external frontoparietal synchronization (FPS) with transcranial alternating current stimulation (tACS) can potentially modulate connectivity within ECN and between ECN and limbic areas. This may improve some aspects of executive function and top down regulation. tACS is a low-cost and scalable non-invasive brain stimulation technology without any serious side effects. The procedure involves the transcranial delivery of low levels of alternating current (0.1-2 mAmp) in different frequencies through the skull into the brain with both online and long-term offline effects. This trial is the first combined tACS/fMRI study to examine the acute offline effects of FPS on neural substrates underlying drug induced craving. We hypothesize that FPS amplifies the ECN top-down modulatory role via its connectivity to other cortical-subcortical areas. In this experimental design, the investigators will recruit 60 people with OUD during the early abstinence phase in a residential setting divided into two parallel arms with active and sham FPS tACS. Each subject will undergo resting state and task based (drug cue exposure paradigm) functional MRI pre and post FPS. The investigators will also conduct individual difference analyses to explore the potential predictors for FPS response, including pre-FPS top-down connectivity measures of ECN and other subjective, clinical, behavioral, structural, and functional variables. The results of this study will provide mechanistic neuroscience-based evidence for the efficacy of FPS and will advance the field towards precision addiction medicine.

Conditions

Opioid-use Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Drug Cue Reactivity BOLD Signal in fMRI from before to after Intervention

  Drug Cue Reactivity BOLD Signal is measured as average blood oxygen level dependent (BOLD) signal difference with voxel-wise analysis in the regions of interests (ROIs) (prefrontal cortex parcels, insula segments, striatum nuclei, thalamus nuclei and extended amygdala nuclei) in craving \> neutral contrast in drug cue exposure fMRI task with blocks of neutral and drug related images

  Immediate before and immediate after intervention

Secondary Outcomes (2)

• Change in Drug Cue Reactivity Self-Report from before to after Intervention

  Immediate before and immediate after intervention

• Change in Cortical-Subcortical Connectivity in Resting State fMRI from before to after Intervention

  Immediate before and immediate after intervention

Other Outcomes (6)

• Change in Cortical-Subcortical Task-based Connectivity in Cue Exposure fMRI from before to after Intervention

  Immediate before and immediate after intervention

• Change in RAI in Resting State fMRI from before to after Intervention

  Immediate before and immediate after intervention

• Change in Area Under Electrode Connectivity in Resting State fMRI from before to after Intervention

  Immediate before and immediate after intervention

Study Arms (2)

Active FPS

EXPERIMENTAL

We use Starstim AC (alternative current) -Stimulator R32. FPS protocol will be used with 20 minutes 2mAmp 6 Hz tACS to the middle frontal gyrus (DLPFC, F4 in EEG electrodes with 10-20 system measurement) and inferior parietal cortex (IPC, P4), as the main nodes of the frontoparietal network, in synchronous oscillation. The 4 return electrodes will receive 0.5 mAmp each around each active electrode (High Definition Montage). The electrodes are silver/silver chloride that are wet with conductive gel. We will use surface landmarks and EEG caps on the head to place the electrodes, which are held in place by head caps with holes indicating places for electrode positioning.

Device: Transcranial Alternating Current Stimulation (tACS)

Sham FPS

SHAM COMPARATOR

In the sham stimulation mode, the device shows pseudorandom numbers on the screen that look like real stimulation is being delivered. The device gives a low level of stimulation at the very beginning and at the very end of the stimulation session (30 seconds ramp up and 30 seconds ramp down) in order to recreate the feeling of tingling that subjects perceive at the beginning and end of real stimulation.

Device: Transcranial Alternating Current Stimulation (tACS)

Interventions

Transcranial Alternating Current Stimulation (tACS) DEVICE

The tACS stimulator delivers very low (2mAmp) current with surface electrodes to the skull.

Active FPS; Sham FPS

Eligibility Criteria

• Age: 18 Years - 61 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Male
• Age ≥18 and \<61 years old
• English speaking
• Diagnosed with Opioid Use Disorder (last 12 months) based on the structured interview (DSM V)
• Being abstinent from opioid in an addiction treatment program for at least 3 days based on medical records or self-report
• Positive response to Opioid cue-reactivity screening (OCS)
• Willing and capable of interacting with the informed consent process

You may not qualify if:

• Unwillingness or inability to complete any of the major aspects of the study protocol, including magnetic resonance imaging (i.e., due to claustrophobia), drug cue rating, or behavioral assessment.
• Abstinence from opioid for more than 6 months based on self-report
• Schizophrenia or bipolar disorder based on the MINI interview
• Active suicidal ideation with intent or plan determined by self-report or assessment by PI or study staff during the initial screening or any other phase of the study
• Positive drug test for amphetamines, opioids, cannabis, alcohol, phencyclidine, or cocaine confirmed by breath analyzer and urine tests
• Any active skin disorder that affects skin integrity of the scalp
• Having any condition that would preclude undergoing an fMRI scan or FPS (tACS) stimulation based on the fMRI safety and transcranial electrical stimulation safety checklists
• Unstable medical disorder reported in subject's medical history or by a clinician assessment
• History of seizure
• Non-correctable vision or hearing problems.
• Any other condition the PI or study staff feel would put the subject at risk for entering the study

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead
• Brain & Behavior Research Foundation: collaborator

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

Transcranial Direct Current Stimulation

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Electric Stimulation Therapy; Therapeutics; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 5, 2019
• First Posted: April 9, 2019
• Study Start: March 15, 2019
• Primary Completion: June 15, 2023
• Study Completion: June 15, 2023
• Last Updated: July 11, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)