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rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder

Primary Purpose

Cocaine Use, Cocaine Dependence, Cocaine Use Disorder

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Active H7-coil repetitive transcranial magnetic stimulation (rTMS)
Sham H7-coil repetitive transcranial magnetic stimulation (rTMS)
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cocaine Use focused on measuring Repetitive transcranial magnetic stimulation, rTMS, TMS, Cognitive behavioral therapy, CBT, Functional magnetic resonance imaging, fMRI

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18-65; Able to give informed consent and comply with study procedures; Meets DSM-5 criteria for current moderate/severe CUD and are treatment-seeking; Used cocaine at least 9 days in the past 28 days, with at least weekly cocaine use; Agree to no more than moderate alcohol consumption (<15 drinks/week for men and <8 drinks/week for women) and to avoid using amphetamine/methamphetamine and non-prescribed benzodiazepines or barbiturates; and Women of childbearing potential must agree to use a method of contraception with proven efficacy and agree to not become pregnant during the study. Exclusion Criteria: Meets DSM-5 criteria for current moderate/severe major depressive episode, OCD, bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to substance use; Hamilton Depression Rating Scale score > 17; Young Mania Rating Scale score >10; Meets DSM-5 criteria for current moderate/severe other substance use disorder (aside from tobacco use disorder; physiologic dependence on any other substance other than nicotine, including alcohol, is exclusionary); Heavy weekly alcohol drinking as defined by an average of >14 drinks/week for men or >7 drinks/week for women on average during the past 28 days; Prior alcohol, benzodiazepine, or barbiturate withdrawal that resulted in hospitalization, medical detoxification, or resulted in seizures or delirium tremens; More than twice weekly use of non-prescribed medications/drugs that may change the seizure threshold, including benzodiazepines, barbiturates, GHB/GBL, amphetamines/methamphetamine; Any other current DSM-5 psychiatric disorder(s) that in the investigator's judgment are unstable, would be disrupted by study procedures, or are likely to require pharmacotherapy or psychotherapy during the study period; Significant current suicide risk, indicated by either: (1) "yes" response on #3, 4, or #5 on the C-SSRS and a psychiatric risk assessment indicating a moderate or high risk of suicide or (2) suicidal behavior in the past 3 months (note: non-suicidal self-injurious behavior is not exclusionary); Females with a positive urine pregnancy test; Clinically significant abnormal cardiac functioning per electrocardiogram (ECG) (required for any participant age 60 years and older); Seizure history including: seizure disorder/epilepsy, alcohol/drug withdrawal seizure, or seizure deemed by the study physician to be related to cocaine intoxication/withdrawal (note: febrile seizures are not exclusionary) Other medical conditions that are relatively contraindicated with TMS (seizure disorders, glaucoma, increased intracranial pressure, severe migraines, stroke, brain lesions, pregnancy or breast-feeding, neurodegenerative disease, meningoencephalitis, intracerebral abscess, parenchymal or leptomeningeal cancers); Medications that lower seizure threshold and in the opinion of the investigator impose significant seizure risk for the individual; Cognitive disorder (MMSE <25); Disqualifying response on the TMS Adult Safety Screen (TASS); Implanted devices or stimulators (cardiac pacemakers, vagus nerve stimulators, spinal cord stimulators, cochlear implant); Currently taking ototoxic medications (aminoglycosides, cisplatin); Metal implants or paramagnetic objects in the body that prohibits MR scanning; Claustrophobia that prohibits MR scanning; or Legally mandated (e.g., to avoid incarceration or other penalties) to participate in SUD treatment program.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Active (high-frequency) rTMS

    Sham (placebo) rTMS

    Arm Description

    Daily high-frequency (10 Hz) repetitive transcranial magnetic brain stimulation for 3 weeks (15 sessions).

    Sham rTMS uses the same device and mimics the auditory and scalp sensations without stimulating the brain.

    Outcomes

    Primary Outcome Measures

    Percentage of participants receiving at least 10 out of 15 rTMS sessions
    Feasibility will be measured as the total percentage of participants who receive the defined number of rTMS sessions
    Number of participants in the active rTMS arm experiencing an rTMS-emergent adverse event
    Safety of rTMS will be measured by the absolute number of serious adverse events that occur in the active rTMS arm
    Percent change of medial prefrontal cortex and dorsal anterior cingulate cortex activity on fMRI during the Drug Stroop Task
    Neural mechanism will be evaluated by comparing the active and sham rTMS groups during the fMRI task by comparing baseline fMRI and post-rTMS fMRI measures
    Percentage of participants who achieve 3 weeks of abstinence during the final 12 weeks of the trial
    Efficacy regarding cocaine use outcomes will be evaluated by comparing the active and sham rTMS groups during the final 12 weeks of the trial while the participants are receiving cognitive behavioral therapy. 3 weeks of consecutive abstinence is defined as: 1. No cocaine use is self-reported per timeline followback; 2. At least 6 urine drug screens are completed during the 3 weeks of continuous abstinence, and all are negative (with the exception of any positive urine in the first 4 days of the first week of the three weeks of self-reported abstinence, as urine may remain positive for up to 4 days after an episode of use), and; 3. At least 1 urine drug screen is completed each week during the 3 weeks of self-reported continuous abstinence.

    Secondary Outcome Measures

    Full Information

    First Posted
    July 26, 2023
    Last Updated
    October 16, 2023
    Sponsor
    New York State Psychiatric Institute
    Collaborators
    National Institute on Drug Abuse (NIDA), Columbia University
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05974202
    Brief Title
    rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder
    Official Title
    Augmenting Cognitive-behavioral Therapy With rTMS of the Medial Prefrontal and Anterior Cingulate Cortices for the Treatment of Cocaine Use Disorder
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    November 15, 2023 (Anticipated)
    Primary Completion Date
    November 2025 (Anticipated)
    Study Completion Date
    November 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    New York State Psychiatric Institute
    Collaborators
    National Institute on Drug Abuse (NIDA), Columbia University

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    Yes
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The goal of this clinical trial is to compare the effects of active repetitive transcranial magnetic stimulation (rTMS) to sham (placebo) rTMS prior to cognitive-behavioral therapy (CBT) as a treatment for adults with cocaine use disorder. The main questions it aims to answer are: Is rTMS safe and feasible as an augmentation for CBT for the treatment of cocaine use disorder? What is the brain mechanism of rTMS? Will active rTMS (compared to sham rTMS) followed by CBT help adults with cocaine use disorder achieve abstinence from cocaine? Participants will: Have two brain MRI scans; Undergo 3 weeks of daily rTMS (or sham) treatments (15 sessions), and; Have 12 weeks of once-weekly cognitive-behavioral therapy for the treatment of cocaine use disorder. Researchers will compare active (real) rTMS to sham (placebo) rTMS. All participants will receive cognitive-behavioral therapy.
    Detailed Description
    Cocaine use disorder (CUD) remains a significant public health problem given that many patients fail to respond to existing therapies (Dutra et al., 2008). Treatment refractory CUD may be explained, in part, by abnormal neurocircuitry. The medial prefrontal cortex (mPFC) and dorsal anterior cingulate cortex (dACC) have demonstrated altered functioning in CUD (Hanlon et al., 2016). Compared to controls, participants with CUD show consistent changes to the mPFC/dACC, including hypoactivation during cognitive and attentional tasks (Bolla et al., 2003; Kaufman et al., 2003; Kubler et al., 2005), hyperactivation during drug cue exposure (Garavan et al., 2000; Grant et al., 1996), and lower grey matter volumes (Ersche et al., 2011; Matochik et al., 2003). Imaging studies also show that these alterations in the mPFC/dACC are associated with an impaired response to treatment. Hypoactivation of the mPFC/dACC region of the fronto-cingular network during the Color-Word Stroop task, a measure of cognitive interference and response inhibition, is associated with faster relapse rates (Brewer et al., 2008). Greater activation of the fronto-cingular network during incongruent stimuli on the Stroop task is also associated with poorer outcomes in CUD participants receiving cognitive behavioral therapy (CBT) (Worhunsky et al., 2013). When using the Drug Stroop task, better performance was associated with a longer duration of cocaine abstinence during CBT (DeVito et al., 2018). Thus, processing deficits across these brain regions likely contribute to the limited success of behavioral interventions for CUD, resulting in high dropout rates and a lack of treatment response. Our goal is to target the mPFC/dACC with repetitive transcranial magnetic stimulation (rTMS) to investigate its impact on neurocognitive function and response to treatment in CUD. We will use the H7-coil, which targets the mPFC/dACC and has been FDA-cleared as a treatment for obsessive-compulsive disorder (Carmi et al., 2019). Previous work by our group showed that high-frequency (10 Hz) rTMS with the H7-coil led to a significant reduction in choices for cocaine in the human laboratory setting (Martinez et al., 2018). Additional studies using rTMS for CUD have targeted the dorsolateral or ventromedial PFC and demonstrated reduction in craving and drug cue reactivity (Ekhtiari et al., 2019; Antonelli et al., 2021; Kearney-Ramos et al., 2018; Kearney-Ramos et al., 2019). Despite these promising findings, sham-controlled clinical trials investigating the effect of rTMS on abstinence and cocaine consumption are lacking. In this trial, our goal is to investigate rTMS as a potential treatment for CUD. Treatment-seeking volunteers with moderate/severe CUD will undergo three weeks (15 daily sessions) of outpatient, randomized, double-blinded, sham-controlled, high-frequency (10 Hz) rTMS to the mPFC/dACC with the H7-coil followed by standardized CBT. We will evaluate feasibility, safety, and the effect of rTMS on the mPFC/dACC using functional magnetic resonance imaging (fMRI) and clinical outcome measures (cocaine use). This outcome data will inform a larger clinical trial to evaluate rTMS as an augmentation for CBT outcomes in moderate/severe CUD and further explore the associated neural mechanisms of rTMS in this clinical population.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Cocaine Use, Cocaine Dependence, Cocaine Use Disorder, Cocaine Use Disorder, Moderate, Cocaine Use Disorder, Severe
    Keywords
    Repetitive transcranial magnetic stimulation, rTMS, TMS, Cognitive behavioral therapy, CBT, Functional magnetic resonance imaging, fMRI

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Model Description
    Active high-frequency stimulation vs. sham (placebo) stimulation
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Masking Description
    Double-blind
    Allocation
    Randomized
    Enrollment
    30 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Active (high-frequency) rTMS
    Arm Type
    Active Comparator
    Arm Description
    Daily high-frequency (10 Hz) repetitive transcranial magnetic brain stimulation for 3 weeks (15 sessions).
    Arm Title
    Sham (placebo) rTMS
    Arm Type
    Placebo Comparator
    Arm Description
    Sham rTMS uses the same device and mimics the auditory and scalp sensations without stimulating the brain.
    Intervention Type
    Device
    Intervention Name(s)
    Active H7-coil repetitive transcranial magnetic stimulation (rTMS)
    Intervention Description
    A magnetic current created by the device creates an electrical current in the brain to stimulate the medial prefrontal cortex and dorsal anterior cingulate cortex.
    Intervention Type
    Device
    Intervention Name(s)
    Sham H7-coil repetitive transcranial magnetic stimulation (rTMS)
    Intervention Description
    A sham coil is in the same helmet as the active coil. The sham coil mimics the sound, scalp sensations, and facial muscle activation caused by the active coil, but does not create an electrical current in the brain.
    Primary Outcome Measure Information:
    Title
    Percentage of participants receiving at least 10 out of 15 rTMS sessions
    Description
    Feasibility will be measured as the total percentage of participants who receive the defined number of rTMS sessions
    Time Frame
    3 weeks
    Title
    Number of participants in the active rTMS arm experiencing an rTMS-emergent adverse event
    Description
    Safety of rTMS will be measured by the absolute number of serious adverse events that occur in the active rTMS arm
    Time Frame
    3 weeks
    Title
    Percent change of medial prefrontal cortex and dorsal anterior cingulate cortex activity on fMRI during the Drug Stroop Task
    Description
    Neural mechanism will be evaluated by comparing the active and sham rTMS groups during the fMRI task by comparing baseline fMRI and post-rTMS fMRI measures
    Time Frame
    3 weeks
    Title
    Percentage of participants who achieve 3 weeks of abstinence during the final 12 weeks of the trial
    Description
    Efficacy regarding cocaine use outcomes will be evaluated by comparing the active and sham rTMS groups during the final 12 weeks of the trial while the participants are receiving cognitive behavioral therapy. 3 weeks of consecutive abstinence is defined as: 1. No cocaine use is self-reported per timeline followback; 2. At least 6 urine drug screens are completed during the 3 weeks of continuous abstinence, and all are negative (with the exception of any positive urine in the first 4 days of the first week of the three weeks of self-reported abstinence, as urine may remain positive for up to 4 days after an episode of use), and; 3. At least 1 urine drug screen is completed each week during the 3 weeks of self-reported continuous abstinence.
    Time Frame
    12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age 18-65; Able to give informed consent and comply with study procedures; Meets DSM-5 criteria for current moderate/severe CUD and are treatment-seeking; Used cocaine at least 9 days in the past 28 days, with at least weekly cocaine use; Agree to no more than moderate alcohol consumption (<15 drinks/week for men and <8 drinks/week for women) and to avoid using amphetamine/methamphetamine and non-prescribed benzodiazepines or barbiturates; and Women of childbearing potential must agree to use a method of contraception with proven efficacy and agree to not become pregnant during the study. Exclusion Criteria: Meets DSM-5 criteria for current moderate/severe major depressive episode, OCD, bipolar disorder, schizophrenia or any psychotic disorder other than transient psychosis due to substance use; Hamilton Depression Rating Scale score > 17; Young Mania Rating Scale score >10; Meets DSM-5 criteria for current moderate/severe other substance use disorder (aside from tobacco use disorder; physiologic dependence on any other substance other than nicotine, including alcohol, is exclusionary); Heavy weekly alcohol drinking as defined by an average of >14 drinks/week for men or >7 drinks/week for women on average during the past 28 days; Prior alcohol, benzodiazepine, or barbiturate withdrawal that resulted in hospitalization, medical detoxification, or resulted in seizures or delirium tremens; More than twice weekly use of non-prescribed medications/drugs that may change the seizure threshold, including benzodiazepines, barbiturates, GHB/GBL, amphetamines/methamphetamine; Any other current DSM-5 psychiatric disorder(s) that in the investigator's judgment are unstable, would be disrupted by study procedures, or are likely to require pharmacotherapy or psychotherapy during the study period; Significant current suicide risk, indicated by either: (1) "yes" response on #3, 4, or #5 on the C-SSRS and a psychiatric risk assessment indicating a moderate or high risk of suicide or (2) suicidal behavior in the past 3 months (note: non-suicidal self-injurious behavior is not exclusionary); Females with a positive urine pregnancy test; Clinically significant abnormal cardiac functioning per electrocardiogram (ECG) (required for any participant age 60 years and older); Seizure history including: seizure disorder/epilepsy, alcohol/drug withdrawal seizure, or seizure deemed by the study physician to be related to cocaine intoxication/withdrawal (note: febrile seizures are not exclusionary) Other medical conditions that are relatively contraindicated with TMS (seizure disorders, glaucoma, increased intracranial pressure, severe migraines, stroke, brain lesions, pregnancy or breast-feeding, neurodegenerative disease, meningoencephalitis, intracerebral abscess, parenchymal or leptomeningeal cancers); Medications that lower seizure threshold and in the opinion of the investigator impose significant seizure risk for the individual; Cognitive disorder (MMSE <25); Disqualifying response on the TMS Adult Safety Screen (TASS); Implanted devices or stimulators (cardiac pacemakers, vagus nerve stimulators, spinal cord stimulators, cochlear implant); Currently taking ototoxic medications (aminoglycosides, cisplatin); Metal implants or paramagnetic objects in the body that prohibits MR scanning; Claustrophobia that prohibits MR scanning; or Legally mandated (e.g., to avoid incarceration or other penalties) to participate in SUD treatment program.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Daniel Brooks, MSW
    Phone
    646-774-8181
    Email
    daniel.brooks@nyspi.columbia.edu
    First Name & Middle Initial & Last Name or Official Title & Degree
    Elizabeth Martinez
    Phone
    212-923-3031
    Email
    elizabeth.martinez@nyspi.columbia.edu
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Derek Blevins, MD
    Organizational Affiliation
    New York State Psychiatric Institute
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Individual participant data that underlie the results published in this report (after de-identification) (text, tables, figures).
    IPD Sharing Time Frame
    Beginning twelve months and ending 5 years after article publication.
    IPD Sharing Access Criteria
    To researcher who provides a methodologically sound proposal to achieve aims in approved proposal.

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    rTMS and Cognitive-behavioral Therapy for Cocaine Use Disorder

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