Cocaine DependenceBRAINSWITCHNCT03333460
Transcranial Magnetic Stimulation for Cocaine Addiction
A study testing Repetitive Transcranial Magnetic Stimulation in people with Cocaine Dependence and Substance Use Disorders, run by ITAB - Institute for Advanced Biomedical Technologies at 2 sites in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Cocaine Dependence, Substance Use Disorders, Chemical Addiction
- What is being tested?
- Repetitive Transcranial Magnetic Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 2 sitesItaly
- Study dates
- 1 Oct 2017to 1 Dec 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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;
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- For female patients: Pregnancy/breastfeeding.
- Subjects who have contraindications to MRI. Some of the exclusions are:
- 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
Trial locations and contacts
2 sites in 1 country.
Italy2 sites, 2 recruiting
- Recruiting
Department of Neuroscience, Imaging and Clinical Sciences
Chieti, 66100
Giovanni Martinotti, MD, PhD, 0039 335 5627362, giovanni.martinotti@gmail.com
Massimo di Giannantonio, MD
- Not yet recruiting
La Promessa ONLUS
Rome, 00192
Mauro Pettorruso, MD, 0039 339 1979487, mauro.pettorruso@hotmail.it
Mauro Pettorruso, MD
About this study
Official title: Cracking Addiction: Does BRAIN Stimulation-induced Neuroplasticity Reverse Prefrontal Cortex Hypoactivity in Cocaine and neW stImulanTs addiCtion in Humans? (BRAIN SWITCH)
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.
Read more
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
Read the 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
- Being tested
- Repetitive Transcranial Magnetic Stimulation
- Keywords
- cocaine, addiction, transcranial magnetic stimulation, neuromodulation, neuroimaging, brain stimulation
- Medical subject headings
- Cocaine-Related Disorders, Substance-Related Disorders, Mental Disorders, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Repetitive Transcranial Magnetic StimulationDevice
Also called rTMS
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).
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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). Receives: Device: Repetitive Transcranial Magnetic Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months
Secondary outcomes (9)
Changes in 90 Symptom Checklist (SCL-90) Global indices
The Symptom Checklist-90 (SCL-90) is a 90-item self-report psychometric instrument. It takes 12-15 minutes to administer. Each item is rated on a scale from 0 (not at all) to 5 (extremely). The global Indices include the General Severity Index (GSI), which is the average rating to all 90 items, the Positive Symptom Total (PST), which is the number of symptoms complained (items scored above zero), and the Positive Symptom Distress Index (PSDI), which is the average rating given to complained symptoms (items scored above zero).
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score
The MADRS is a 10-item scale that evaluates the core symptoms and cognitive features of clinical depression. Each MADRS item is rated on a 0 to 6 scale. The MADRS Total score ranges from 0 (min) to 60 (max). Higher MADRS scores indicate higher levels of depressive symptoms.
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score
The HAM-A is a 14-item scale that assesses anxiety symptoms of anxiety such as "anxious mood", "tension" or "fears". Each item is scored on a 5-point scale, ranging from 0 (not present) to 4 (severe). Sum the scores from all 14 parameters gives the HAM-A Total Score which may range from 0 (min) to 56 (max).
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in the Frontal Assessment Battery (FAB) Total Score
Frontal Assessment Battery (FAB) is a short neuropsychological tool aimed at assessing executive functions. The FAB consists of six subtests, each exploring functions related to the frontal lobes: conceptualization (by means of a similarities task), mental flexibility (by means of a phonological fluency task), motor programming (by means of Luria's motor series), sensitivity to interference (by means of a conflicting instructions task), inhibitory control (by means of a go-no-go task), and environmental autonomy (by means of evaluation of prehension behavior). Each subtest score may range from 0 (min) to 3 (max); total score is from 0 (min) to 18 (max). Higher scores indicate better performance.
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Eriksen Flanker Test
The Eriksen Flanker Task is a set of response inhibition tests used to assess the ability to suppress responses that are inappropriate in a particular context. The target is flanked by non-target stimuli which correspond either to the same directional response as the target (congruent flankers), to the opposite response (incongruent flankers), or to neither (neutral flankers). A directional response (usually left or right) is assigned to a central target stimulus. Each task begin with a short instruction phase followed by 20 practice trials and 100 experimental trials. The stimuli are displayed for 1500 msec. The measures of performance in each condition is the median reaction time (RT) for correct trials and the proportion of errors.
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in the Iowa Gambling Task (IGT) Performance
The Iowa Gambling Task is a computerized card game commonly used to measure risky decision making tendencies and sensitivity to reward and loss. Performance is calculated on the total net score results from the subtraction of the disadvantageous deck choices from the advantageous deck choices during the entire test ([C'+D']-[A'+B']).
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Snaith Hamilton Pleasure Scale (SHAPS) Total Score
The Snaith Hamilton Pleasure Scale (SHAPS) is a 14-item self-report scale designed to measure hedonic-tone/anhedonia. Each item is scored on a 4-point scale, ranging from 0 (not at all) to 3 (extremely). Sum the scores from all 14 parameters gives the SHAPS Total Score which may range from 0 (min) to 42 (max).
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Temporal experience of Pleasure Scale (TEPS) Total Score
The Temporal experience of Pleasure Scale (TEPS) is a 18-item self-report scale designed to evaluate individual trait dispositions in anticipatory and consummatory pleasure experiences. Each item is scored on a 6-point scale, ranging from 1 (extremely false) to 6 (extremely true). Sum the scores from all 20 parameters gives the TEPS Total Score which may range from 20 (min) to 108 (max).
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Profile of Mood States (POMS), Total Mood Disturbance Score
The profile of mood state (POMS) is a questionnaire designed to measure present mood state by a list of adjectives on a 5-point Likert scale (0 = not at all; 4 = Extremely) and measures six dimensions of affect, including tension-anxiety, depression-dejection, anger-hostility, vigor-activity, fatigue-inertia, and confusion-bewilderment. The measure has been shown to produce reliable and valid profiles of mood state. A Total Mood Disturbance Score may be calculated by adding the scores for Tension, Depression, Anger, Fatigue and Confusion and then subtracting the score for Vigour.
Measured: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2017
- Study start1 Oct 2017
- Primary completion1 Dec 2020 (estimated)
- Study completion1 Dec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cocaine DependenceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- ITAB - Institute for Advanced Biomedical Technologies
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Giovanni Martinotti, ITAB - Institute for Advanced Biomedical Technologies
- Investigators
- Massimo di Giannantonio, MD, Principal investigator, Department of Neuroscience, Imaging and Clinical Sciences (ITAB) - University G. d'Annunzio - Chieti (Italy)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03333460
- Sponsor's protocol ID
- v.1_8/05/2017
- Acronym
- BRAINSWITCH
- Status last verified
- Nov 2017
- First submitted
- 21 Sep 2017
- Last updated
- 7 Nov 2017
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35074451Pettorruso 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.
PubMed 29885861
Study at a glance
From the registry record, last updated by the sponsor on 7 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cracking Addiction: Does BRAIN Stimulation-induced Neuroplasticity Reverse Prefrontal Cortex Hypoactivity in Cocaine and neW stImulanTs addiCtion in Humans? (BRAIN SWITCH)
- ClinicalTrials.gov ID
- NCT03333460
- Acronym / sponsor ID
- BRAINSWITCH / v.1_8/05/2017
- 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 type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- ITAB - Institute for Advanced Biomedical TechnologiesUniversity, hospital or other
- Study start
- 1 Oct 2017 (actual)
- Primary completion
- 1 Dec 2020 (estimated)
- Study completion
- 1 Dec 2020 (estimated)
- First posted
- 7 Nov 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- double blind, randomized, sham-controlled with a 1:1 allocation into 2 parallel arms
| Arm | Type | Receives |
|---|---|---|
| Active Comparator: Active rTMS (15 Hz) | Experimental | Device: Repetitive Transcranial Magnetic StimulationThe 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). |
| Sham Comparator: Sham rTMS (15 Hz) | Placebo comparator | Device: Repetitive Transcranial Magnetic StimulationThe 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (14 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Repetitive Transcranial Magnetic StimulationAlso: rTMSrTMS 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). | Device | Active Comparator: Active rTMS (15 Hz), Sham Comparator: Sham rTMS (15 Hz) |
Primary outcome
Change in the Brief Version of Cocaine Craving Questionnaire (Brief-CCQ) Total score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
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.
Change in cocaine consumption as assessed by Timeline Follow Back (TLFB)
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months
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.
Change in cocaine consumption as assessed by Urine Drug Screen (UDS)
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months
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.
9 secondary outcomes
Changes in 90 Symptom Checklist (SCL-90) Global indices
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Montgomery-Asberg Depression Scale (MADRS) Total Score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Hamilton Rating Scale for Anxiety (HAM-A) Total Score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in the Frontal Assessment Battery (FAB) Total Score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Eriksen Flanker Test
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in the Iowa Gambling Task (IGT) Performance
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Snaith Hamilton Pleasure Scale (SHAPS) Total Score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Temporal experience of Pleasure Scale (TEPS) Total Score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Changes in Profile of Mood States (POMS), Total Mood Disturbance Score
Time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Nov 2017.
- Derived from this study: PubMed 35074451Martinotti 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.
- Derived from this study: PubMed 29885861Pettorruso 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Massimo di Giannantonio, MD principal investigator
Department of Neuroscience, Imaging and Clinical Sciences (ITAB) - University G. d'Annunzio - Chieti (Italy)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Repetitive Transcranial Magnetic Stimulation in people with Cocaine Dependence and Substance Use Disorders, run by ITAB - Institute for Advanced Biomedical Technologies at 2 sites in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 7 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Giovanni Martinotti, MD, PhD (0039 0871 3556914, giovanni.martinotti@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Brief Version of Cocaine Craving Questionnaire (Brief-CCQ) Total score (time frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03333460, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Nov 2017.