Contingency Management Plus Deep Transcranial Magnetic Stimulation for the Treatment of Cocaine Use Disorder

Official title

Contingency Management Plus Deep Transcranial Magnetic Stimulation for the Treatment

Overview

The purpose of this study is to evaluate the effects of Contingency Management (CM)+transcranial magnetic stimulation (TMS) on treatment outcomes in individuals who are initial non-responders and to evaluate the effects of CM+TMS on putative mechanisms of change

Interventions

• Behavioral Contingency Management (CM)
  Participants will have thrice-weekly (Monday, Wednesday and Friday) clinic visits, during which participants can earn rewards for submitting a cocaine-negative UDS.CM sessions will consist of the following components: 1) brief discussion of any substance use/cravings since prior CM session; 2) verification that the target behavior (abstinence) was achieved; 3) if achieved, provide incentives and discuss individual plans to use the earnings; 4) if not achieved, review the goals of CM and plans to
• Device Transcranial Magnetic Stimulation (TMS) Sham
  The sham stimulations with negligible induced electric fields, delivered via the same H4 coil to mimic the acoustic characteristics and scalp sensations of active H4 will be used.
• Device Transcranial Magnetic Stimulation (TMS) experimental
  Participants will sit comfortably in a chair with head support and wear protective earplugs. A Brainsway Deep TMS system model 104 with an H4 coil will be used. Following the standardized procedure, the H4 coil is held by a mechanical arm and positioned 6 cm anterior to the motor spot.Duration: The proposed H4 coil-delivered accelerated TMS protocol will use iTBS for 3 sessions a day, 3 days a week, for 6 weeks (54 sessions) followed by two weeks of 3 sessions a day (6 additional maintenance ses

Primary outcome measures

• Number of participants who test negative for cocaine use as assessed by urine drug screen [Time frame: from Baseline to Week 11]
• Cocaine craving as assessed by cocaine craving questionnaire (CCQ) [Time frame: from Baseline to Week 11]

Secondary outcome measures (4)

• Change in Cue-induced craving as assessed by VAS during cue task [Time frame: Baseline, Week 2, Week 11]
• Change in amplitude of the Late Positive Potential (LPP) in Microvolts in Response to Visual Stimuli on the Picture Viewing Task as Assessed by EEG [Time frame: Baseline, Week 2, Week 11]
• Change in Functional Connectivity between the Bilateral anterior insula (AIn) and central amygdala (CeA) as measured by Functional Magnetic Resonance Imaging (fMRI) [Time frame: Baseline, Week 2, Week 11]
• Change in Phenotype assessment battery (PhAB) as assessed by addiction domains of cognition, reward, and negative emotionality [Time frame: Baseline, Week 2, Week 11]

Eligibility criteria

Inclusion criteria

• Able to provide informed consent before any study-related activity, willing to comply with all study procedures, and be available for the duration of the study.
• Meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) diagnostic criteria for moderate-to-severe CUD and report recent cocaine use (verified by at least one positive urine drug screen (UDS) for the cocaine metabolite benzoylecgonine (BE), during intake).
• Agree (if the participant is female and of child-bearing potential) to use effective contraceptive methods, unless the participant's male partner(s) is surgically sterile (underwent vasectomy).

Acceptable contraceptives include:

• oral contraceptives
• contraceptive sponge
• patch
• double barrier (diaphragm/spermicidal or condom/spermicidal)
• intrauterine contraceptive system
• etonogestrel implant
• medroxyprogesterone acetate contraceptive injection
• complete abstinence from sexual intercourse
• hormonal vaginal ring

Contraceptive measures sold for emergency use after unprotected sex are not acceptable methods for routine use.

• Women of child-bearing potential must provide negative urine pregnancy test prior to randomization.
• Be able to provide the names and contact information of at least 2 persons who can consistently locate their whereabouts

Exclusion criteria

• Current DSM-5 diagnosis for substance use disorder (of at least moderate severity) other than cocaine, cannabis, or nicotine or a substance Use Disorder (SUD) requiring medical detoxification (e.g., alcohol, opioid, benzodiazepine)
• Presence of any medical, neurological, psychiatric, or physical condition, disease, or illness (including psychosis and bipolar disorder) that, in the opinion of the PIs and the Certified Registered Nurse Anesthetist (CNRA)Medical Director could: (a) compromise interfere, limit, or reduce the subject's ability to complete the study; or (b) adversely impact the safety of the subject or the integrity of the data.
• Has current or recent (within 3 months of potential enrollment) suicidal ideation, suicidal behavior, homicidal ideation or a homicidal plan sufficient to raise subject safety concerns based on the following assessments:

• Structured Clinical Interview for DSM-5 (SCID-5)
• Columbia-Suicide Severity Rating Scale - Answers YES to Questions 3, 4, 5, or 6
• Assault \& Homicidal Danger Assessment Tool - Key to Danger > 1
• Any contraindications to MRI scans (metal in the body; claustrophobia). -Medical implants contraindicating TMS (i.e., aneurysm clips or coils, stents, implanted stimulators, implanted vagus nerve or deep brain stimulators, implanted electrical devices such as pacemakers or medication pumps, electrodes for monitoring brain activity, cochlear implants for hearing, any magnetic implants, bullet fragments, any other metal device or object implanted in your body closer than 30 cm from the coil).
• History of brain surgery.
• History of an intracranial lesion or any medical or neurological diagnosis/condition associated with increased intracranial pressure (i.e., Idiopathic Intracranial Hypertension/Pseudotumor Cerebri) OR any of the following symptoms within 30 days of enrollment: headaches > 15 days/month, loss of vision or decreased vision
• Moderate-to-severe heart disease.
• History of stroke.
• Taking any antidepressant or antipsychotic medication at a dose above the maximum recommended dose or at a dose deemed to be potentially unsafe according to the study physician; has taken any of the following medications, which are known to increase the risk of seizures, within 1 week of study enrollment; or does not agree to abstain from taking the following medications during study participation:

• clozapine
• chlorpromazine
• bupropion
• clomipramine hydrochloride
• amoxapine
• maprotiline hydrochloride
• diphenhydramine
• stimulants other than cocaine including the following:
• Dextroamphetamine and amphetamine ii. Dextroamphetamine iii. Lisdexamfetamine dimesylate iv. Methamphetamine

v. Methylphenidate i. tramadol j. isoniazid.

• Personal history of epilepsy or seizure disorder and/or family history including a first degree relative
• Serious head injury with loss of consciousness
• Having conditions of probation or parole requiring reports of drug use to officers of the court or impending incarceration
• For adolescent aged participants (18-21 only): any risk factor for neurocardiogenic syncope (history of syncope/ presyncope related to noxious stimuli, anxiety, micturition, or posture).
• Pregnant or nursing for female participants
• Inability to read, write, or speak English.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Texas Health Science Center at Houston — Houston

Identifiers

NCT: NCT07490600 · HSC-MS-25-0782 · 1U01DA064181-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗