10 Days of Theta Burst Stimulation as a Tool to Treat Cocaine Dependence

10 Days of Medial Prefrontal Cortex Theta Burst Stimulation (MPFC cTBS) as a Tool to Improve Clinical Outcomes and Decrease Frontal-striatal Reactivity to Cues Among Treatment-engaged Cocaine and Alcohol Users

The goal of this double-blind sham controlled study is to evaluate the effeicacy of continuous theta burst stimulation to the frontal pole as a tool to decrease drug cue reactivity and improve treatment outcomes in treatment-engaged cocaine and alcohol users. All participants will be randomized to receive 10 days of real or sham rTMS to the frontal pole. Brain imaging data and behavioral assessments will be collected at 4 time points - before TMS, after 10 days of TMS, 1 month follow up and 2 month follow up.

Study Overview

• Status: Completed
• Conditions: Alcohol Dependence; Cocaine Dependence
• Intervention / Treatment: Device: Real cTBS; Device: Sham cTBS

Detailed Description

Cocaine dependence is a particularly difficult substance use disorder to treat. There is currently a lot of scientific inertia focused on the development of novel, neural circuit based strategies for intervention. A prior NARC funded pilot project in non-treatment seeking cocaine users demonstrated that a single session of medial prefrontal cortex theta burst stimulation (MPFC cTBS) decreases baseline frontal-striatal activity in limbic regions and decreases neural responses to cocaine uses. The effects of a single session however, erode over the first few hours after treatment. Sustainable effects require multiple days of treatment. GOAL: The next steps in pursuing this as a novel treatment are to 1) apply it to treatment-engaged patients and 2) determine whether several sessions of cTBS will produce sustainable and clinically-meaningful changes in cocaine use among these patients.

DESIGN: Treatment-engaged cocaine users and heavy alcohol users will be randomized to receive 10 sessions of real or sham LTD-like MPFC cTBS. This will be achieved by leveraging our existing partnership with the MUSC Center for Drug and Alcohol Programs (CDAP) and the Veterans Administration Substance Abuse Treatment Center Program (SATC) - which both provide a 4 week intensive outpatient treatment program. MPFC cTBS will be given during weeks 2 and 3 of the program. Functional MRI data and clinical assessments will be acquired during weeks 1, 4, and at participant's 1 month and 2 month Accountability/Continuity visits. Hypothesis: real cTBS treatment will enhance clinical outcomes (Aim 1 - including retention rates, number of clean urine drug screens during CDAP treatment, relapse rates at 1 and 2 months) and will produce a sustainable decrease in neural reactivity to cocaine cues (Aim 2 - week 1 versus week 4, 1 month & 2 month follow ups).

• Study Type: Interventional
• Enrollment (Actual): 84
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
    • Charleston, South Carolina, United States, 29425
      • Ralph H Johnson Veterans Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Individuals from 21-65 years old currently enrolled in an intensive outpatient treatment program.

Exclusion Criteria:

• Participants will be excluded if they are not between 21-65 years old, have current or prior dependence (DSM-IV, because a DSM-V version of the SCID is not yet available) on prescription or psychoactive drugs other than cocaine, alcohol, or nicotine but including marijuana; past 6 month abuse of any prescription or psychoactive drugs excluding cocaine, marijuana, alcohol or nicotine, lifetime history of head injury with loss of consciousness, being pregnant or breast feeding, unstable medical illness (e.g., hypertension, diabetes, myocardial infarction), presence of ferromagnetic metal in their body, history of seizures. Additionally, to mitigate any potential risk of seizures. As mentioned above, all participants will receive the Clinical Institute Withdrawal Assessment of Alcohol (CIWAar) assessment before each TMS visit. Individuals with a CIWA score >5 will be excused from the study. All individuals with a history of medical detoxification or hospitalization for AUD (per the Assessments listed above), self-reported alcohol withdrawal seizures, or delirium tremens will be excluded from the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Real cTBS; 10 days of real cTBS treatment will be given (3600 pulses to the left frontal pole as defined by EEG coordinate: FP1; 60 second pause after 1800 pulses; 110% RMT including a 30 second initial ramp period 80%-110% RMT; Magventure MagPro X100 Cool Coil).	Device: Real cTBS; This will be delivered with the Magventure Magpro system; 3600 pulses with the active sham coil (double blinded using the USB key)
SHAM_COMPARATOR: Sham cTBS; 10 days of sham cTBS treatment will be given (3600 pulses to the left frontal pole as defined by EEG coordinate: FP1; 60 second pause after 1800 pulses; 110% RMT including a 30 second initial ramp period 80%-110% RMT; Magventure MagPro X100 Cool Coil).	Device: Sham cTBS; This will be delivered with the sham Magventure Magpro system; 3600 pulses with the active sham coil (double blinded using the USB key)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Drug cue reactivity	The effect of real versus sham cTBS on drug cue reactivity will be assessed by comparing the brain activity in the limbic system	Baseline visit and 1 month follow up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Clean Urine Drug Screens	The effect of real versus sham cTBS on the number of clean urine drug screens will be assessed at the 1 and 2 month follow up.	1 month and 2 month follow up

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: National Institute on Drug Abuse (NIDA)

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2016
• Primary Completion (ACTUAL): June 7, 2019
• Study Completion (ACTUAL): June 7, 2019

Study Registration Dates

• First Submitted: September 1, 2016
• First Submitted That Met QC Criteria: July 31, 2017
• First Posted (ACTUAL): August 3, 2017

Study Record Updates

• Last Update Posted (ACTUAL): March 12, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Alcoholism; Cocaine-Related Disorders
• Other Study ID Numbers: 00046438; R21DA041610 (NIH)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No individual participant data will be shared. All data is deidentified.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No