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Mechanism of Non-invasive Magnetic Stimulation

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03394066
Recruitment Status : Recruiting
First Posted : January 9, 2018
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute on Drug Abuse (NIDA) )

Brief Summary:

Background:

Transcranial magnetic stimulation (TMS) is form of non-invasive brain stimulation. It is approved to treat depression. TMS may help decrease drug craving. It is important to understand how TMS affects the brain. Such a better understanding would help to design ways to treat drug addiction.

Objectives:

To learn how TMS affects the brain when it stimulates an area in the front of the brain. Also, to see how the stimulation affects the area stimulated and other connected areas.

Eligibility:

Healthy, right-handed adults ages 18 60 who are non-drug users.

Design:

Participants will be screened under protocol 06-DA-N415.

Participants will have at least 3 visits. The first visit will last about 3 hours. All other visits will last up to 6 hours. Participants cannot use drugs or alcohol at least 24 hours before a visit. They cannot have more than half a cup of a caffeinated drink at least 12 hours before a visit.

Each visit will include a brief medical history update, urine test for drugs and pregnancy (if female), a breath test for alcohol and smoking, and questionnaires.

Participants will have a TMS orientation visit. A wire coil will be placed on the head. An electrical current will pass through the coil to create a magnetic pulse that stimulates the brain.

The other visits will include 2 sessions of TMS-MRI. Participants will lie on a table that slides into a cylinder. The TMS coil and the MRI coil will be placed over the head. Pictures will be taken of the brain with and without stimulation.

Participants will complete a questionnaire about how they feel before and after each TMS session and in a follow-up call 2 3 weeks after their last session.


Condition or disease Intervention/treatment Phase
Healthy Volunteers Device: TMS Phase 1

Detailed Description:

Objectives: The goal of the protocol is to investigate acute modulations of brain activity by transcranial magnetic stimulation (TMS). Using simultaneous TMS and functional magnetic resonance imaging (fMRI), we will evaluate TMS induced changes in brain activity, including regional brain activation and inter-regional functional connectivity. Repetitive TMS will be applied over the dorsolateral prefrontal cortex (DLPFC) with different frequencies and interleaved with fMRI acquisition to provide online monitoring of brain activity. Furthermore, we will assess the relationship between the TMS induced brain activity and the anatomical connection obtained from diffusion tensor imaging (DTI), using individual variations in these imaging measures. Results from this study will help to understand the underling mechanism of TMS and will provide insights for interpretation of TMS and fMRI data.

Study population: Up to 70 healthy, adults will be tested. Subjects must fit exclusion/inclusion criteria for both TMS and MRI. We expect to enroll 70 subjects to arrive at 50 who complete the protocol.

Design: The study is a within-subject design with each subject completing up to 4 TMS-fMRI sessions in two days (2 sessions per day)

Outcome measures: The outcome measures will be the effects of TMS on fMRI blood oxygen level-dependent (BOLD) responses, TMS induced changes on resting state functional connectivity, and their associations with relevant structural connectivity revealed by DTI.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Understanding the Acute Modulation of Brain Activity by Transcranial Magnetic Stimulation
Actual Study Start Date : August 2, 2018
Estimated Primary Completion Date : October 1, 2020
Estimated Study Completion Date : December 31, 2022

Arm Intervention/treatment
Active Comparator: TMS
All participants will receive TMS
Device: TMS
Transcranial Magnetic Stimulation device




Primary Outcome Measures :
  1. Effects of TMS on fMRI blood oxygen level-dependent (BOLD) responses, TMS induced changes on resting state functional connectivity, and their associations with relevant structural connectivity revealed by DTI. [ Time Frame: at TMS visits ]
    fMRI blood oxygen level-dependent (BOLD) responses, TMS induced changes on resting state functional connectivity, and their associations with relevant structural connectivity revealed by DTI.



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 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Subjects must:

  • Be able to give valid informed consent
  • Be 18 60 years of age.

    • Justification: Many neural processes change with age, and these changes could introduce unwanted variability in both behavioral and MRI signals. In addition, the risk of difficult-to-detect medical abnormalities such as silent cerebral infarcts increases with age.
    • Screening tool: History. Government-issued forms of identification (e.g. driver s license, birth certificate) will be required when participant appears to be out of age range.
  • Be in good health.

    • Justification: Many illnesses may alter neural functioning as well as fMRI signals.
    • Screening tools: Medical Assessment, Medical History and Physical Examination. Medical assessments include: Vital Signs, EKG, oral HIV test, height/weight measurements, urinalysis and blood sample. Tests on the blood sample include CBC, complete metabolic profile, TSH, ESR, STS and HIV (if needed to confirm a positive salivary test for HIV). The following individual laboratory results will independently disqualify individuals: Cholesterol >250 mg/dl, Hemoglobin < 10.5 g/dl, WBC < 2400/ (Micro)l, LFTs > 3Xnormal, HCG positive, Casual serum glucose > 200 mg/dl, Urine protein > 1+. The MAI will retain discretion to exclude at less extreme values, depending on the clinical presentation. (Serum glucose over 140 mg/dl will be followed up with a fasting serum glucose assessment. Those with fasting glucose below 100 mg/dl may be considered for the protocol. Others will be rejected and referred for work-up.) MAI will make the final judgment on any questionable lab results.
  • Right-handed.

    • Justification: Using right-handed individuals will reduce variability in BOLD MRI data.
    • Screening tool: Edinburgh Handedness Inventory.

EXCLUSION CRITERIA:

  • Personal history of stroke, brain lesions, previous neurosurgery, any personal history of seizure or fainting episode of unknown cause, or head trauma resulting in loss of consciousness, lasting over 30 minutes or with sequela lasting longer than two days.

    • Justification: Stroke or head trauma can lower the seizure threshold, and are therefore contra-indications for TMS. Fainting episodes or syncope of unknown cause could indicate an undiagnosed condition associated with seizures.
    • Screening tool: TMS safety questionnaire, Medical History.
  • First-degree family history of any neurological disorder with a potentially hereditary basis, including migraines, epilepsy, or multiple sclerosis.

    • Justification: Neurological disorders can lower the seizure threshold, and are therefore contra-indications for TMS. First-degree family history of certain neurological disorders with a hereditary component increases the risk of the subject having an undiagnosed condition that is associated with lowered seizure threshold.
    • Screening tool: TMS safety screening, Medical History.
  • Cardiac pacemakers, neural stimulators, implantable defibrillator, implanted medication pumps, intracardiac lines, or acute, unstable cardiac disease, with intracranial implants (e.g. aneurysm clips, shunts, stimulators, cochlear implants, or electrodes) or any other metal object within or near the head that precludes MRI scanning.

    • Justification: Any metal around the head is a contraindication for both MRI and TMS, as both methods involve exposure to a relatively strong magnetic field.
    • Screening tool: TMS safety screening, MRI safety screening, Medical History.
  • Noise-induced hearing loss or tinnitus.

    • Justification: individuals with noise-induced hearing problems may be particularly vulnerable to the acoustic noise generated by TMS and MRI equipment.
    • Screening tools: TMS safety screening.
  • Current use (any use in the past 4 weeks, chronic use within 6 past six months) of any investigational drug or of any medications with psychotropic, anti or pro-convulsive action.

    • Justification: The use of certain medications or drugs can lower seizure threshold and is therefore contraindicated for TMS.
    • Screening tools: MRI safety screening questionnaire, Medical history, Medical Assessments: Urine toxicology analyzes for presence of a broad range of prescription and nonprescription drugs.
  • Lifetime history of major depressive disorder, schizophrenia, bipolar disorder, mania, or hypomania.

    • Justification: The population of interest here is a healthy control population with no psychiatric disorders. In subjects with depression, bipolar disorder, mania or hypomania, there is a small chance that TMS can trigger (hypo)manic symptoms.
    • Screening tools: MINI Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor.
  • Current use of nicotine or history more than 20 cigarettes lifetime or history of daily smoking.

    • Justification: The population of interest here is a healthy control population with no substance use disorder and therefore a minimal cigarette exposure history in the control group is required.
    • Screening tools: Self-report, urine cotinine (e.g. NicAlert) level of 2, CO < 6.
  • Meet current DSM-5 criteria for any substance use disorder, smoke daily, or urine toxicology positive for any illicit substance inconsistent with history given.

    • Justification: The population of interest here is a healthy control population with no substance use disorder. Current use of illicit substances could lower seizure threshold and is therefore contraindicated for TMS.
    • Screening tools: MINI Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor, Drug Use Survey (DUS), Substance Use Disorder Evaluation, Medical Assessments: urine qualitative drug screen is performed for methadone, benzodiazepines, cocaine, amphetamine/methamphetamine, opiates, barbiturates, and tetrahydrocannabinol. Participants who test positive at screening (under protocol 06-DA-N415) will be evaluated with a neuromotor exam to further assess for current intoxication. For participants who are not found to be currently intoxicated, screening staff will assess for SUD and coherence of their drug use history and toxicology, with particular attention to substances for which they are positive and may require a return screening visit to demonstrate ability to produce a negative urine before allowing them to proceed to clearance for this study.
  • Have met DSM-5 criteria for any substance use disorder in the past.

    • Justification: the population of interest here is a healthy control population with no present or past substance use disorder.
    • Screening tools: MINI Screen Patient Questionnaire. Potential diagnoses will be further evaluated by a counsellor. Drug Use Survey (DUS), Substance Use Disorder Evaluation.
  • History of myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, or any heart condition currently under medical care.

    • Justifications: the risk of TMS for individuals with a heart condition is unknown.
    • Screening tool: physical assessment (EKG), medical history.
  • Pregnant women or women with reproductive potential who are sexually active and not using an acceptable form of contraception.

    • Justification: it is unknown whether TMS or MRI poses a risk to fetuses.
    • Screening tool: Medical assessments (urine pregnancy test) at the beginning of each visit that involves TMS or MRI.
  • Participation in an rTMS session less than two weeks ago.

    • Justification: in order to limit exposure to TMS, we will not enroll subjects who have received TMS less than two weeks ago.
    • Screening tool: TMS safety screening questionnaire.
  • Learning disability, ADHD or cognitive impairment

    • Justification: Cognitive impairment and learning disabilities are associated with alterations in brain regions and may introduce significant variably into the data.
    • Screening tool: self-report of special education classes, history of specific learning disability or mental retardation, Wechsler Abbreviated Scale of Intelligence (WASI), Medical history and Adult ADHD Self-Report Scale with follow up clinical interview.

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): NCT03394066


Contacts
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Contact: Yihong Yang, Ph.D. (443) 740-2648 yihongyang@mail.nih.gov

Locations
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United States, Maryland
National Institute on Drug Abuse Recruiting
Baltimore, Maryland, United States, 21224
Contact: Yihong Yang, Ph.D.    443-740-2648    yihongyang@mail.nih.gov   
Sponsors and Collaborators
National Institute on Drug Abuse (NIDA)
Investigators
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Principal Investigator: Yihong Yang, Ph.D. National Institute on Drug Abuse (NIDA)
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Responsible Party: National Institute on Drug Abuse (NIDA)
ClinicalTrials.gov Identifier: NCT03394066    
Other Study ID Numbers: 999918042
18-DA-N042
First Posted: January 9, 2018    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: October 31, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute on Drug Abuse (NIDA) ):
Repetitive TMS (rTMS)
Simultaneous TMS and MRI