Transcranial Magnetic Stimulation for Cocaine Addiction

NCT ID: NCT03333460

Last Updated: 2017-11-07

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-10-01
• Study Completion Date: 2020-12-01

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

Detailed Description

Repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce craving in cocaine addicts. However, the efficacy of rTMS in treating cocaine addiction has not been evaluated in double-blind, sham-controlled studies and also, we lack a full characterization of rTMS effects on other important aspects, including effects on mood, cognition and changes in brain function. The purpose of this study is to investigate the effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 15 Hz frequency on the left dorsolateral prefrontal cortex in cocaine dependent patients and to examine possible changes in mood, cognition, and brain activity and functional connectivity associated with this intervention. For this purpose, the investigators will recruit cocaine dependent patients. After screening and informed consent, participants will undergo active or sham rTMS for two consecutive weeks (twice a day) during the continued treatment phase, and a maintenance intervention (twice a week for 3 months), during the rTMs follow-up phase. Following this phase, participants will be followed for further 3 months, during which no rTMS will be delivered but clinical and imaging data will be collected. The investigators will also measure clinical, cognitive and brain structural and functional connectivity to assess changes related to the intervention in the short and long term (measurements at: baseline, 2 weeks, 3 months, 6 months).

Procedure: The project consists of: Screening Visit (baseline), Part 1 (continued treatment phase), Part 2 (3 months- rTMS follow-up), Part 3 (3 months follow-up without rTMS). First, there will be a screening visit, where a clinical interview will be conducted and questionnaires and tests will be administered to identify study participants who meet the inclusion and exclusion criteria. Baseline clinical, cognitive and neuroimaging data will be acquired. The neuroimaging data will be exploratory, to be associated with the outcome measures. In Part 1, all participants will be randomly assigned to one of the two treatment arms with rTMS (15Hz, 15Hz-Sham). Participants will receive 2 sessions of rTMS (active or sham), twice per day for 10 consecutive days, for a total of 20 rTMS sessions. Following this, the investigators will evaluate the acute effect of treatment on cocaine craving and consumption, mood and cognition. Also, they will collect exploratory neuroimaging data (functional MRI and resting state functional connectivity). In Part 2 of the study, all participants will continue the assigned treatment arm with rTMS (15Hz, 15Hz-Sham) for three months. Participants will receive 2 sessions of rTMS (active or sham) once per week; clinical and cognitive data will be acquired once per month. The investigators will evaluate the effect of treatment on cocaine craving and consumption, mood and cognition. Also, they will collect exploratory neuroimaging data (functional MRI and resting state functional connectivity). In Part 3 of the study, participants will not receive any rTMS session. Clinical and cognitive data will be acquired once per month for three months. The investigators will evaluate the long-term effect of treatment on cocaine craving and consumption, mood and cognition.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active Comparator: Active rTMS (15 Hz)

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).

Group Type: EXPERIMENTAL

Repetitive Transcranial Magnetic Stimulation

Intervention Type: 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).

Sham Comparator: Sham rTMS (15 Hz)

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).

Group Type: PLACEBO_COMPARATOR

Repetitive Transcranial Magnetic Stimulation

Intervention Type: 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).

Interventions

Repetitive Transcranial Magnetic Stimulation

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).

Intervention Type: DEVICE

Other Intervention Names

rTMS

Eligibility Criteria

Inclusion Criteria

1. Current diagnosis of cocaine use disorder (from moderate to severe), based on the Diagnostic and Statistical Manual of Mental Disorder - Fifth Edition (DSM-5);

2. Abstinence from cocaine for at least 48 hrs.

Exclusion Criteria

1. Current DSM-5 diagnosis of substance and/or alcohol use disorders other than nicotine;

2. Current DSM-5 diagnosis of schizophrenia, bipolar disorder, or other psychotic disorder;

3. 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);

4. 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;

5. Any personal or family history (1st degree relatives) of seizures other than febrile childhood seizures;

6. 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;

7. For female patients: Pregnancy/breastfeeding.

8. Subjects who have contraindications to MRI. Some of the exclusions are:

1. 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.

2. Unable to lie flat on the back for the expected length of the experiment (50 minutes).

3. Have an abnormality on the brain imaging or neurologic examination not related to the diagnosis.

4. Uncomfortable being in a small space for the expected length of the experiment (50 minutes).

5. Non-removable body piercing or tattoo posing MRI risk

6. Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ITAB - Institute for Advanced Biomedical Technologies

OTHER

Sponsor Role: lead

Responsible Party

Giovanni Martinotti

Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Massimo di Giannantonio, MD

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Department of Neuroscience, Imaging and Clinical Sciences

Chieti, , Italy

Site Status: RECRUITING

La Promessa ONLUS

Rome, , Italy

Site Status: NOT_YET_RECRUITING

Countries

Italy

Central Contacts

Giovanni Martinotti, MD, PhD

Role: CONTACT

Phone: 0039 0871 3556914

Email: giovanni.martinotti@gmail.com

Mauro Pettorruso, MD

Role: CONTACT

Phone: 0039 3391979487

Email: mauro.pettorruso@hotmail.it

Facility Contacts

Giovanni Martinotti, MD, PhD

Role: primary

Mauro Pettorruso, MD

Role: primary

References

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.

Reference Type: DERIVED

PMID: 35074451 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 29885861 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

v.1_8/05/2017

Identifier Type: -

Identifier Source: org_study_id