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Treatment With Transcranial Magnetic Stimulation for Cocaine Addiction: Clinical Response and Functional Connectivity. (TMS_COC_CONN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02986438
Recruitment Status : Unknown
Verified July 2017 by Jorge J. González Olvera, Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente.
Recruitment status was:  Recruiting
First Posted : December 8, 2016
Last Update Posted : July 24, 2017
Sponsor:
Collaborator:
National Council of Science and Technology, Mexico
Information provided by (Responsible Party):
Jorge J. González Olvera, Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente

Brief Summary:
The purpose of this study is to investigate the short and long term clinical and cognitive effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 5 Hz and/or 10 Hz frequencies on the left dorsolateral prefrontal cortex in cocaine dependent patients and to examine possible changes in brain structure and functional connectivity associated with this intervention.

Condition or disease Intervention/treatment Phase
Cocaine-Related Disorders Device: Repetitive Transcranial Magnetic Stimulation Device: Repetitive Transcranial Magnetic Stimulation (Sham) Not Applicable

Detailed Description:

Repetitive transcranial magnetic stimulation (rTMS) has been shown to reduce craving in cocaine addicts in the short term. However, there are no studies on the long term clinical and cognitive effects of sustained rTMS therapy. Moreover, clinical improvement or decline could be related to long term changes in brain structure and function. The purpose of this study is to investigate the short and long term clinical and cognitive effects of repetitive Transcranial Magnetic Stimulation (rTMS) at 5 Hz and/or 10 Hz frequencies on the left dorsolateral prefrontal cortex in cocaine dependent patients and to examine possible changes in brain structure and functional connectivity associated with this intervention. For this purpose the investigators will recruit cocaine dependent patients and stimulate them using rTMS with a acute intervention (twice a day for 2 weeks) and a maintenance intervention (twice a week for 12 months). The investigators will follow the patients to determine clinical outcome. The investigators will also measure clinical, cognitive and brain structural and functional connectivity to asses changes related to the intervention in the short and long term (measurements at: baseline, 2 weeks, 3 months, 6 months and 12 months).

Procedure:

The projects consists of: Screening Visit, Part 1 and Part 2.

First, there will be a screening visit, where a clinical interview will be conducted and tests will be applied to select study participants who meet the inclusion and exclusion criteria.

Baseline clinical, cognitive and neuroimaging data will be acquired. The cognitive and neuroimaging data will be exploratory, to be associated with the outcome measures. Part 1 of the study entails the determination of the rTMS target frequency (5 or 10 Hz) for Part 2 (long term stimulation). In Part 1, all participants will be randomly assigned to one of the four treatment legs with rTMS (10Hz, 10Hz-Sham, 5Hz, 5Hz-Sham). Participants will receive 20 sessions of rTMS (intervention or sham), twice per day for 10 consecutive days. Each session lasts approximately 35 minutes.

At 2 weeks, the investigators will evaluate the short term effect of treatment by measuring clinical, cognitive and neuroimaging changes and select which frequency of stimulation is the most effective in terms of clinical improvement, but also in terms of the rate of secondary effects. Our hypothesis is that 5 Hz is as effective as 10 Hz without the high rate of secondary effects (i.e. seizures).

In Part 2 of the study, the sham groups will end and they will be invited to the treatment condition although they data not will be considered for later phases. Here the maintenance phase starts (long term), where rTMS will be performed twice a week for 12 months using the target frequency (5 or 10 Hz). Clinical, cognitive and neuroimaging data will be acquired at 3, 6 and 12 months.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of Transcranial Magnetic Stimulation on Functional Connectivity and Response to Treatment of Cocaine Dependent Patients
Actual Study Start Date : May 1, 2017
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Active rTMS frequency at 5 Hz
The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive treatment stimulation in the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 5 Hz, that includes 2 sessions per day for 10 consecutive business days for 2 weeks. Then a target frequency will be determined for the remaining of the study. If this arm's target frequency is chosen, then the participants will receive the maintenance intervention of 2 sessions per week for 12 months. Each session will consist of the application of rTMS at a frequency of 5Hz, to 100% of the motor threshold.
Device: Repetitive Transcranial Magnetic Stimulation

The investigators will use a Magpro R-30 MagVenture quick stimulator, equipped with an 8-reel, 75 mm internal diameter in each spiral.

Each patient will receive consistent treatment in 2 sessions a day for 10 consecutive business days in the first two weeks, then receive 2 weekly sessions, until the year of treatment is completed. Each session will consist of the application of 30 trains of 10 seconds duration separated by intervals of one minute, at a fixed frequency (5Hz or 10Hz), to 100% of the motor threshold.


Sham Comparator: Sham rTMS frequency at 5 Hz
The intervention will be Repetitive Transcranial Magnetic Stimulation (Sham). rTMS will be used with a coil that allows simulated stimulation (Coil AP) at a frequency of 5 Hz, with the software necessary for the operator to remain blind to the stimulation condition. This arm will only last for 2 weeks.
Device: Repetitive Transcranial Magnetic Stimulation (Sham)

The investigators will use a Magpro R-30 MagVenture quick stimulator, equipped with an 8-reel, 75 mm internal diameter in each spiral with a coil that allows simulated stimulation (Coil AP).

This condition will only last two weeks.


Active Comparator: Active rTMS frequency at 10 Hz
The intervention will be Repetitive Transcranial Magnetic Stimulation. Each patient will receive treatment stimulation in the left dorsolateral prefrontal cortex (lDLPFC) with a frequency of 10 Hz, that includes 2 sessions per day for 10 consecutive business days for 2 weeks. Then a target frequency will be determined for the remaining of the study. If this arm's target frequency is chosen, then the participants will receive the maintenance intervention of 2 sessions per week for 12 months. Each session will consist of the application of rTMS at a frequency of 10 Hz, to 100% of the motor threshold.
Device: Repetitive Transcranial Magnetic Stimulation

The investigators will use a Magpro R-30 MagVenture quick stimulator, equipped with an 8-reel, 75 mm internal diameter in each spiral.

Each patient will receive consistent treatment in 2 sessions a day for 10 consecutive business days in the first two weeks, then receive 2 weekly sessions, until the year of treatment is completed. Each session will consist of the application of 30 trains of 10 seconds duration separated by intervals of one minute, at a fixed frequency (5Hz or 10Hz), to 100% of the motor threshold.


Sham Comparator: Sham rTMS frequency at 10 Hz
The intervention will be Repetitive Transcranial Magnetic Stimulation. rTMS will be used with a coil that allows simulated stimulation (Coil AP) at a frequency of 10 Hz, with the software necessary for the operator to remain blind to the stimulation condition. This arm will only last for 2 weeks.
Device: Repetitive Transcranial Magnetic Stimulation (Sham)

The investigators will use a Magpro R-30 MagVenture quick stimulator, equipped with an 8-reel, 75 mm internal diameter in each spiral with a coil that allows simulated stimulation (Coil AP).

This condition will only last two weeks.





Primary Outcome Measures :
  1. Change in Cocaine Craving (CCQ) [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    The craving will be measured using a craving questionnaire for cocaine validated in Mexican population (Cocaine Craving Questionnaire or CCQ) before and after each treatment of rTMS.

  2. Change in Cocaine Craving (VAS) [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    The craving will be measured using a 100 mm visual analogue scales (VAS).

  3. Lapse rate [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Lapse is defined as at least one consumption event not in the same pattern as the baseline consumption. The report of self-consumption of cocaine and urine drug tests, with special attention to the presence of traces of cocaine.

  4. Relapse rate [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Relapse is defined as consumption events in the same pattern as the baseline consumption. The report of self-consumption of cocaine and urine drug tests, with special attention to the presence of traces of cocaine.


Secondary Outcome Measures :
  1. Changes in Psychopathological Symptoms [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Measured by the 90 Symptoms Questionnaire (SCL-90).

  2. Changes in Depression [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Measured by Hamilton Depression Rating Scale (HDRS) (21 items).

  3. Changes in Anxiety [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Measured by Hamilton Anxiety Rating Scale (HARS).

  4. Changes in Drug Consumption and Related Problems [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Measured by the Addiction Severity Index (ASI-lite).

  5. Changes in Sleep Quality. [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Measured by the Pittsburgh Sleep Quality Index (PSQI).

  6. Changes in Impulsivity [ Time Frame: Baseline, after rTMS treatment: 2 weeks, 3 months, 6 months, 12 months. ]
    Measured by the Barrat Impulsivity Scale-11 (BIS-11).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Minimum age of eighteen and maximum of fifty years.
  • Cocaine users for at least 2 years, currently using at least 3 times a week, with abstinence periods continuing to be less than one month in the last year.
  • The reading level of at least 6th grade of primary (equivalent to fifth grade of elementary school).
  • The ability to give a valid informed consent.
  • Right-handed (in order to control by cerebral laterality in Neuroimaging).
  • If the subject is female and of childbearing age, she agrees to use a medically acceptable form of contraception, and to not become pregnant during the duration of the study. A woman is considered to have potential for pregnancy, unless she is postmenopause or surgically sterilized. Female patients of childbearing potential should use either: (1) contraceptive pill or hormone preparation IUD or deposit (ring, injection, implant); And / or (2) a barrier method of contraception, such as the diaphragm, spermicide sponge, or a condom.

Contraceptive measures will be reviewed with the female subjects at each visit prior to the rTMS treatment.

  • Self-report of experiencing cocaine craving when exposed to cocaine-associated cues.
  • Body mass index less or equal to 30, allowing them to safely enter the Magnetic Resonance.

Exclusion Criteria:

  • Personal or first-degree family history of any clinically defined neurological disorder, including organic brain disease, epilepsy, brain events, brain injury, or multiple sclerosis; Or personal history of previous neurosurgery or traumatic brain injury that have produced loss of consciousness.
  • Cardiac pacemakers, neural stimulators, implantable defibrillators, implanted medication pumps, intracardiac lines, or acute, unstable heart disease, with intracranial implants (eg, aneurysm clips, leads, stimulators, cochlear implants, or electrodes) or with any other Metallic object inside or near the head that can not be safely removed.
  • Screw metal or metallic projectiles into the head or body.
  • Current use of any investigational drug or any anti-proconvulsant drug such as tricyclic or neuroleptic antidepressants (which reduce the seizure threshold).
  • Increased intracranial pressure (decreasing seizure threshold).
  • History of depressive disorder, schizophrenia, bipolar disorder, mania or hypomania.
  • History of myocardial infarction, angina pectoris, congestive heart failure, cardiomyopathy, cerebrovascular events or transient ischemic attack, or any heart condition currently under medical care.
  • Women with reproductive potential who do not use an acceptable form of contraception pregnant or who are lactating.
  • Any history of seizures.
  • The current dependence (DSM-V criteria) on substances other than cocaine and / or nicotine.
  • Claustrophobia making them unable to tolerate lying inside the MRI scanner.
  • History of HIV infection or HIV antibody test positive (Due to potential neuroinfection).

These data will be corroborated by a screening visit where the following instruments will be used:

Clinical Interview. Self-applicable demographic questionnaire. Mini International Neuropsychiatric Interview (MINI-Plus). Structured clinical interview for DSM Axis II, self report (SCID-II).

Elimination criteria:

The participation of all participants during the study will be suspended if:

  • They express their desire to stop participating.
  • They present abnormal radiological findings that require more attention outside the study to ensure the health of the participant.
  • Worsening of clinical condition.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02986438


Contacts
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Contact: Jorge J González Olvera, MD, PHD +525541605349 jjgonz@gmail.com
Contact: Eduardo A Garza Villarreal, PHD +525541605354 egarza@gmail.com

Locations
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Mexico
Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente Recruiting
Mexico City, Mexico, 14370
Contact: Ruth Alcala, MD, MSc    +52(55)41605065    tratamiento.inprfm@gmail.com   
Contact: Eduardo Garza-Villarreal, MD, PhD    +52(55)41605354    tratamiento.inprfm@gmail.com   
Sponsors and Collaborators
Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
National Council of Science and Technology, Mexico
Investigators
Layout table for investigator information
Principal Investigator: Jorge J González, MD, PHD Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
Principal Investigator: Eduardo A Garza Villarreal, PHD Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente

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Responsible Party: Jorge J. González Olvera, Principal Investigator, Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente
ClinicalTrials.gov Identifier: NCT02986438    
Other Study ID Numbers: IC16036.0
First Posted: December 8, 2016    Key Record Dates
Last Update Posted: July 24, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: After the main publications by the group are released, all data (clinical, cognitive and neuroimaging) will be uploaded to an online open server such as LONI or OpenfMRI, for example.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Jorge J. González Olvera, Instituto Nacional de Psiquiatría Dr. Ramón de la Fuente:
Cocaine
Addiction
rTMS
fMRI
Additional relevant MeSH terms:
Layout table for MeSH terms
Cocaine-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Cocaine
Anesthetics, Local
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents
Vasoconstrictor Agents
Dopamine Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Dopamine Agents
Neurotransmitter Agents