Transcranial Magnetic Stimulation for Cocaine Addiction

NCT03333460 | Unknown

• 1 other identifier: v.1_8/05/2017
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

Background: Cocaine use disorders (CUD) is a complex brain disorder, involving several brain areas and neurocircuits. Effective treatments for CUD are still needed. Repetitive transcranial magnetic stimulation (rTMS) stimulates non-invasively parts of the brain. Preliminary data suggest that rTMS may help reducing cocaine craving and consumption. Researchers want to learn how the brain and the drug-seeking behavior may change with this treatment. Objectives: To test if rTMS can reduce cocaine craving and use, and also affect several mood, behavioral and cognitive alterations associated with prolonged cocaine use. Eligibility: Healthy, right-handed adults ages 18-65 who do have cocaine use disorder (moderate to severe). Design: This is a randomized, double-blind, sham-controlled study. The study includes three phases: 1) a rTMS continued treatment phase; a rTMS follow-up; and a no rTMS follow-up. Prior to participating, participants will be screened with:

• Questionnaires
• Medical history
• Physical exam
• Urine tests
• MRI (structural) After being enrolled, baseline behavioral and imaging data will be collected. In particular, participants will undergo:
• Questionnaires
• Functional MRI During the continued rTMS phase, participants with cocaine use disorder will be randomized to receive real or fake rTMS. Repetitive TMS will be delivered during 10 outpatient treatment days, over 2 weeks (5 days/week). Following this phase, subjects will have 12 follow-up visits (once/weekly), during which they will receive rTMS, and behavioral and imaging assessments will be performed. At the end of the rTMS follow up period, participants will further receive 3 follow up visits (once a month), during which rTMS will not be performed, but behavioral data will be collected. Treatment includes:
• rTMS: A coil is placed on the head. A brief electrical current passes through the coil. At each visit, participants will receive two rTMS sessions, with a 1hr interval between sessions. At the beginning of each rTMS session, they view cocaine-related images for few minutes.
• MRIs at baseline and at follow-up visit #12: Participants lie on a table that slides into a cylinder that takes pictures of the brain. They respond to images while in the scanner.
• Repeat of screening tests and questionnaires
• Urine toxicological screen

Conditions

Cocaine Dependence; Substance Use Disorders; Chemical Addiction; Mental Disorder; Cocaine-Related Disorders; Drug Dependence

Keywords

cocaine; addiction; transcranial magnetic stimulation; neuromodulation; neuroimaging; brain stimulation

Outcome Measures

Primary Outcomes (3)

• Change in the Brief Version of Cocaine Craving Questionnaire (Brief-CCQ) Total score

  Brief Version of Cocaine Craving Questionnaire (Brief-CCQ) is a 10-item scale that evaluates craving for cocaine. Each Brief-CCQ item is rated on a 1 to 7 scale. The Brief-CCQ Total score ranges from 10 (min) to 70 (max). Higher Brief-CCQ scores indicate higher cocaine craving levels.

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months

• Change in cocaine consumption as assessed by Timeline Follow Back (TLFB)

  Cocaine consumption will be assessed using the TimeLine Follow Back (TLFB). TLFB is an interview-based assessment. Using a calendar, participants are guided through the process of recalling and reporting daily substance consumption. TLFB provides measures of cocaine consumption per week, cocaine consuming days per week, heavy cocaine consuming days per week.

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months

• Change in cocaine consumption as assessed by Urine Drug Screen (UDS)

  Cocaine consumption will be evaluated by Urine Drug Screen (UDS). Urine Drug Screen is a painless test to evaluate the presence of cocaine and other substances of abuse in urine samples. Quantitative analyses are not performed. Test may be positive or negative for the presence of cocaine and other substances.

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months

Secondary Outcomes (9)

• Changes in 90 Symptom Checklist (SCL-90) Global indices

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months

• Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months

• Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months

• Changes in the Frontal Assessment Battery (FAB) Total Score

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months

• Changes in Eriksen Flanker Test

  Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months

Study Arms (2)

Active Comparator: Active rTMS (15 Hz)

EXPERIMENTAL

The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive active stimulation targeting the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 15 Hz and 100% of the individual resting motor threshold, for a total of 40 trains (60 stimuli per train, inter-train interval of 15 second, total duration 13 minutes). Each session will be repeated twice/daily for 10 consecutive days for 2 weeks, during the continued treatment phase. Following this, the participants will receive the maintenance intervention of 2 sessions per week for 3 months (rTMS follow-up), at the same parameters described above. Device: MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Device: Repetitive Transcranial Magnetic Stimulation

Sham Comparator: Sham rTMS (15 Hz)

PLACEBO COMPARATOR

The intervention will be Repetitive Transcranial Magnetic Stimulation (Sham). rTMS will be used with the software necessary for the operator to remain blind to the stimulation condition. Also, the software will be pre-programmed by a staff member that will not be involved in data collection and analysis. The sham condition will match the number of pulses delivered during the 15Hz session and will use the same coil placement but the intensity of stimulation will be set a 3% of the individual resting motor threshold so to ensure that the participant will feel similar scalp sensations experienced by participants receiving active rTMS, but brain tissue will not be stimulated. Device: MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

Repetitive Transcranial Magnetic Stimulation DEVICE

rTMS is a non-invasive brain stimulation technique. The investigators will use a MagPro R30 with the Cool-B80 figure-of-eight coil (MagVenture, Falun, Denmark).

Also known as: rTMS

Active Comparator: Active rTMS (15 Hz); Sham Comparator: Sham rTMS (15 Hz)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Current diagnosis of cocaine use disorder (from moderate to severe), based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);
• Abstinence from cocaine for at least 48 hrs.

You may not qualify if:

• Current DSM-5 diagnosis of substance and/or alcohol use disorders other than nicotine;
• Current DSM-5 diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder;
• Use in the past 4 weeks of any medication with known pro-convulsant action; or current regular use of any psychotropic medications (benzodiazepines, antipsychotic medications, tricyclic antidepressants, anti-epileptics, mood stabilizers);
• Any history of any clinically significant neurological disorder, including organic brain disease, epilepsy, stroke, brain lesions, multiple sclerosis, previous neurosurgery, or personal history of head trauma that resulted in loss of consciousness for \> 5 minutes and retrograde amnesia for \> 30 minutes;
• Any personal or family history (1st degree relatives) of seizures other than febrile childhood seizures;
• Any psychiatric, medical or social condition whether or not listed above, due to which, in the judgment of the PI and after any consults if indicated, participation in the study is not in the best interest of the patient;
• For female patients: Pregnancy/breastfeeding.
• Have non-MRI compatible metal in the body, such as a cardiac pacemaker, brain stimulator, shrapnel, surgical metal, clips in the brain or on blood vessels, cochlear implants, artificial heart valves or ferromagnetic fragments in the eye or oral cavity as these make having an MRI unsafe.
• Unable to lie flat on the back for the expected length of the experiment (50 minutes).
• Have an abnormality on the brain imaging or neurologic examination not related to the diagnosis.
• Uncomfortable being in a small space for the expected length of the experiment (50 minutes).
• Non-removable body piercing or tattoo posing MRI risk
• Pregnancy

Sponsors & Collaborators

• ITAB - Institute for Advanced Biomedical Technologies: lead

Study Sites (2)

Department of Neuroscience, Imaging and Clinical Sciences

Chieti, 66100, Italy

RECRUITING

La Promessa ONLUS

Rome, 00192, Italy

NOT YET RECRUITING

Related Publications (2)

• Martinotti G, Pettorruso M, Montemitro C, Spagnolo PA, Acuti Martellucci C, Di Carlo F, Fanella F, di Giannantonio M; Brainswitch Study Group. Repetitive transcranial magnetic stimulation in treatment-seeking subjects with cocaine use disorder: A randomized, double-blind, sham-controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2022 Jun 8;116:110513. doi: 10.1016/j.pnpbp.2022.110513. Epub 2022 Jan 22.

  PMID: 35074451 DERIVED

• Pettorruso M, Spagnolo PA, Leggio L, Janiri L, Di Giannantonio M, Gallimberti L, Bonci A, Martinotti G. Repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex may improve symptoms of anhedonia in individuals with cocaine use disorder: A pilot study. Brain Stimul. 2018 Sep-Oct;11(5):1195-1197. doi: 10.1016/j.brs.2018.06.001. Epub 2018 Jun 5. No abstract available.

  PMID: 29885861 DERIVED

MeSH Terms

Conditions

Cocaine-Related Disorders; Substance-Related Disorders; Mental Disorders; Behavior, Addictive

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Chemically-Induced Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Massimo di Giannantonio, MD

  Department of Neuroscience, Imaging and Clinical Sciences (ITAB) - University G. d'Annunzio - Chieti (Italy)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Giovanni Martinotti, MD, PhD

CONTACT

0039 0871 3556914; giovanni.martinotti@gmail.com

Mauro Pettorruso, MD

CONTACT

0039 3391979487; mauro.pettorruso@hotmail.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: With regard to the treatment, to ensure that both participants and investigators are blind to the condition (active or sham), the selection of the operation mode (15 Hz, sham) will be pre-programmed by member of the that will not be involved in data collection and analysis. Study personnel will not know which mode is being activated. Sham stimulation will use the same coil placement as that used for active stimulation. Outcomes Assessors will not be present during the rTMS sessions.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Researcher

Model Details: double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms

Study Record Dates

• First Submitted: September 21, 2017
• First Posted: November 7, 2017
• Study Start: October 1, 2017
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2020
• Last Updated: November 7, 2017

Record last verified: 2017-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2)