U01DA064181

CONTINGENCY MANAGEMENT PLUS DEEP TRANSCRANIAL MAGNETIC STIMULATION FOR THE TREATMENT OF COCAINE USE DISORDER - PROJECT SUMMARY THE PREVALENCE OF COCAINE USE DISORDER (CUD) IN THE UNITED STATES IS INCREASING, NOW AFFECTING APPROXIMATELY 1.4 MILLION, ALONGSIDE A SIGNIFICANT RISE IN THE RATE OF COCAINE-INVOLVED OVERDOSES. IN THE ABSENCE OF FDA- APPROVED MEDICATIONS, TREATMENT OPTIONS FOR CUD ARE LIMITED TO BEHAVIORAL APPROACHES, WITH CONTINGENCY MANAGEMENT (CM) CONSIDERED THE MOST EFFECTIVE. HOWEVER, RESEARCH BY OUR GROUP AND OTHERS HAS SHOWN THAT RESPONSES TO CM VARY CONSIDERABLY, WITH POORER TREATMENT OUTCOMES ASSOCIATED WITH PHENOTYPIC CHARACTERISTICS IN THE DOMAINS OF COGNITION, REWARD, AND NEGATIVE EMOTIONALITY. THIS STUDY AIMS TO DEVELOP A NOVEL TREATMENT COMBINATION BY PAIRING BEHAVIORAL THERAPY (CM) WITH TRANSCRANIAL MAGNETIC STIMULATION (TMS) THAT TARGETS BRAIN CIRCUITY ALTERATIONS ASSOCIATED WITH CM EFFECTS, WITH THE GOAL OF IMPROVING TREATMENT REFRACTORINESS. BASIC BEHAVIORAL NEUROSCIENCE RESEARCH HAS INDICATED THAT THE ANTERIOR INSULAR (AIN) – AMYGDALA PATHWAY PLAYS A KEY ROLE IN PSYCHOSTIMULANT ABSTINENCE AND RELAPSE IN RODENT MODELS OF CM. UNTIL RECENTLY, TRADITIONAL TMS DEVICES COULD ONLY STIMULATE A FOCAL AREA DIRECTLY UNDER THE SKULL. RECENT ADVANCES IN BRAIN STIMULATION TECHNIQUES ALLOW FOR TARGETING THESE DEEPER STRUCTURES. SPECIFICALLY, THE ‘DEEP TMS’ H4 COIL STIMULATES THE INSULA AND LATERAL PREFRONTAL CORTEX (PFC) BILATERALLY, MAKING IT POSSIBLE TO TARGET CM-CRITICAL PATHWAYS. FURTHER, THE INSULA AND PFC ARE CRITICAL HUBS FOR COGNITION, REWARD, AND NEGATIVE EMOTIONALITY PHENOTYPES ASSOCIATED WITH CM, SUCH THAT H4-DELIVERED TMS COULD POTENTIALLY CORRECT THESE PHENOTYPIC CHARACTERISTICS LINKED TO TREATMENT REFRACTORINESS. THIS STUDY WILL USE A NOVEL TWO-STAGE DESIGN TO EVALUATE THE EFFECTS OF CM PLUS H4 TMS FOR TREATING CUD. IN THE FIRST 4 WEEKS OF TREATMENT, ALL PARTICIPANTS (N = 130) WILL RECEIVE HIGH-MAGNITUDE CM TO IDENTIFY TREATMENT REFRACTORINESS, WITH INITIAL ‘RESPONSE’ TO CM DEFINED AS ACHIEVING TWO WEEKS OF CONSECUTIVE COCAINE-NEGATIVE URINES. PARTICIPANTS WHO DO NOT RESPOND (‘NON-RESPONDERS’) WILL ENTER THE TMS AUGMENTATION PROTOCOL AND BE RANDOMIZED TO RECEIVE EITHER ACTIVE OR SHAM DEEP H4 TMS THERAPY, IN ADDITION TO CM, FOR ANOTHER 8 WEEKS. THE ACCELERATED TMS PROTOCOL WILL CONSIST OF THREE SESSIONS OF INTERMITTENT THETA BURST STIMULATION (ITBS), DELIVERED THRICE WEEKLY FOR SIX WEEKS THEN ONCE WEEKLY FOR TWO WEEKS. PRIMARY OUTCOMES WILL INCLUDE ABSTINENCE (PROPORTION OF RESPONDERS), REDUCED COCAINE USE (PERCENT NEGATIVE URINES), AND CHANGE IN CRAVING AS ASSESSED THROUGH SELF-REPORT AND CUE-INDUCED ELECTROENCEPHALOGRAM BRAIN RESPONSES (AIM 1). RESTING-STATE FUNCTIONAL CONNECTIVITY (RSFC) AND THE NIDA PHENOTYPING ASSESSMENT BATTERY (PHAB) WILL BE CONDUCTED AT THREE TIMEPOINTS TO EXPLORE TREATMENT MECHANISMS ASSOCIATED WITH THE PROPOSED PATHWAY (AIM 2). MACHINE LEARNING TECHNIQUES WILL INTEGRATE DATA ACROSS MODALITIES (RSFC; PHAB) TO PRELIMINARILY DEVELOP A PREDICTIVE MODEL AIMED AT IDENTIFYING INITIAL NON-RESPONDERS WHO ARE MOST LIKELY TO BENEFIT FROM CM+TMS TREATMENT (EXPLORATORY AIM). IF SUCCESSFUL, THE RESULTS OF THIS STUDY COULD PAVE THE WAY TOWARD FDA CLEARANCE OF A COMBINATION (CM+TMS) PRODUCT TAILORED TO INDIVIDUALS WITH TREATMENT-REFRACTORY PHENOTYPES.

University Of Texas Health Science Center At Houston

TO SUPPORT BASIC AND CLINICAL NEUROSCIENCE, BIOMEDICAL, BEHAVIORAL AND SOCIAL SCIENCE, EPIDEMIOLOGIC, HEALTH SERVICES AND HEALTH DISPARITY RESEARCH. TO DEVELOP NEW KNOWLEDGE AND APPROACHES RELATED TO THE PREVENTION, DIAGNOSIS, TREATMENT, ETIOLOGY, AND CONSEQUENCES OF DRUG ABUSE AND ADDICTION, INCLUDING HIV/AIDS. TO SUPPORT RESEARCH TRAINING AND RESEARCH SCIENTIST DEVELOPMENT. TO SUPPORT DISSEMINATION OF RESEARCH FINDINGS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) LEGISLATION IS INTENDED TO EXPAND AND IMPROVE THE SBIR PROGRAMS TO EMPHASIZE AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF TECHNOLOGY DEVELOPED THROUGH FEDERAL SBIR RESEARCH AND DEVELOPMENT, INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN THE SBIR PROGRAM. THE LEGISLATION INTENDS THAT THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM STIMULATE AND FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.279 - Drug Abuse and Addiction Research Programs

National Institute on Drug Abuse (NIDA) [HHS - NIH]

Texas United States

State-Wide

Combined Neuromodulation and Behavioral Treatment Algorithm Development for Stimulant Use Disorder (StUD) Enriched for Vulnerable Phenotype (U01 Clinical Trial Required) (RFA-DA-25-057)