Neuropharmacological Imaging for Addiction

Recruiting at 1 trial location

Overseen By NIDA IRP Screening Team

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Institute on Drug Abuse (NIDA)

Must not be taking: Psychoactive, Vascularly active

Disqualifiers: Pregnancy, Metallic implants, Major psychiatric, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 9

1000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to develop new MRI techniques to better understand how drug addiction affects the brain. Researchers will use advanced imaging methods, including the Magnetom Prisma Fit 3T Scanner, to study brain changes and activity in both drug users and non-users. Participants will undergo MRI scans, which may involve completing specific tasks or experiencing controlled conditions like carbon dioxide exposure. Generally healthy adults aged 18 to 80, whether they use drugs or not, are suitable for this trial. As an unphased trial, it offers participants the opportunity to contribute to groundbreaking research that could lead to better understanding and treatment of drug addiction.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are using psychoactive or vascularly active medications, you might need to discuss this with the researchers, as these could affect certain MRI techniques.

What prior data suggests that these MRI techniques are safe for brain imaging studies related to addiction?

Research has shown that transcranial magnetic stimulation (TMS) is generally safe. TMS uses magnetic fields to stimulate nerves in the brain and has received FDA approval for treating major depression, indicating it is usually well-tolerated. Common side effects are minor, such as headaches or discomfort at the application site, and are easy to manage. Serious side effects are rare.

The transcranial rotating magnetic stimulator (TRPMS) also has a promising safety record. TRPMS functions like TMS but uses a rotating magnetic field. Studies have shown that its side effects are minor and similar to those of TMS.

Both TMS and TRPMS are non-invasive, meaning they don't involve surgery or implants, making them relatively safe options. Prospective trial participants can feel confident that these methods have been thoroughly studied and are generally safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's exploring innovative ways to understand and treat addiction using advanced brain imaging techniques. Unlike standard treatments that primarily focus on behavioral therapies or medications, this trial uses cutting-edge tools like the Magnetom Prisma Fit 3T Scanner to study brain activity in real-time. By combining transcranial magnetic stimulation (TMS) with functional MRI (fMRI), the trial aims to uncover how different levels of brain stimulation affect brain excitability and activity. This could lead to more precise and effective interventions for addiction, potentially offering new paths for treatment that go beyond current methods.

What evidence suggests that this trial's treatments could be effective for addiction?

Research shows that transcranial magnetic stimulation (TMS) can help treat addiction by reducing cravings and the chance of relapse. Several studies have found that repetitive TMS (rTMS) lowers cravings for substances like cocaine, nicotine, and alcohol. In this trial, participants in the TMS-fMRI Experiment 1 arm will undergo TMS to evaluate its effects on brain activity related to cravings and self-control. Meanwhile, the TRPMS Experiment 1 and 2 arms will explore the effects of transcranial rotating magnetic stimulation (TRPMS) on motor cortex excitability and cortical excitability changes. Early evidence suggests that these non-invasive brain stimulation methods might also improve mood and thinking in people with substance use disorders. Although more research is needed, these findings are promising for those struggling with addiction. ^{2 6 7 8 9}

Who Is on the Research Team?

Yihong Yang, Ph.D.

Principal Investigator

National Institute on Drug Abuse (NIDA)

Are You a Good Fit for This Trial?

Adults aged 18-80, including smokers and non-smokers, drug users and non-users. Participants must be able to consent and understand English. Exclusions include pregnancy, metal implants that affect MRI safety, high seizure risk conditions, severe psychiatric or neurological disorders, major medical illnesses like heart disease or diabetes.

Inclusion Criteria

All subjects must be able to provide informed consent

Exclusion Criteria

Subjects with neurological illnesses severe enough to impact data being gathered

Pregnant individuals

Subjects unable to undergo MRI scanning due to implanted metallic devices or claustrophobia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

MRI Methodology Development and Evaluation

Participants undergo MRI scans for methodology development and evaluation, including pulse sequence development, testing, and parameter optimization.

Up to 4 visits, each visit up to 4 hours

Up to 4 visits (in-person)

TMS-fMRI Experiment

Participants undergo TMS-fMRI scans to evaluate the relationship between BOLD activation and MEP, establishing a BOLD activation marker of cortical excitability.

6-8 hours

1 visit (in-person)

TRPMS Experiment

Participants undergo TRPMS sessions to evaluate the prolonged effect on motor cortex excitability and cortical excitability changes measured with simultaneous TMS-fMRI.

2-6 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the experimental sessions.

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Magnetom Prisma Fit 3T Scanner
• Magnetom Prisma Fit 3T Scanner (Siemens)
• MagPro X100 Magnetic Stimulator
• Transcranial Rotating Magnetic Stimulator

Trial Overview The trial is developing new MRI techniques for addiction studies. It involves an initial screening with questionnaires followed by a series of MRI scans lasting about 2 hours each. Some scans may require tasks or study the brain's response to carbon dioxide.

How Is the Trial Designed?

Group I: TRPMS Experiment 2 Experimental Treatment 2 Interventions

To evaluate cortical excitability changes caused by TRPMS measured with simultaneous TMS-fMRI. Participants will undergo a baseline TMS/fMRI session to get a measurement of baseline cortical excitability in the form of single-pulse TMS induced BOLD activation and determine motor hot-spot and RMT. We will then conduct an event-related single-pulse TMS/fMRI session with TMS stimulus at 120% RMT, 50 events with jittered inter-stimulus-interval (ISI) averaging 16s. Simultaneous EMG recording will be gathered from the corresponding hand muscle. Next we will use TRPMS to stimulate the left motor cortex over the hot-spot : 20-min application of TRPMS, 100ms duration, 0.2Hz (one stimulus every 5s), total 240 stimuli. Then we will evaluate the modulatory effect of the TRPMS stimulation via a second TMS/fMRI session with a similar procedure as the baseline session using the RMT determined at baseline. Total time for this experiment is about 5-6 hours.

Group II: TRPMS Experiment 1 Experimental Treatment 1 Intervention

To evaluate the prolonged effect of TPRMS on motor cortex excitability and help interpret and design subsequent experiments investigating the effect of TRPMS on BOLD signal. The experiment design consists of four groups, each group will include 10 participants (8 completers/group). For TRPMS stimulation sessions, our test conditions will be a 10 stimuli-session (approximately 2min), 50 stimuli-session (approximately 7min), 100 stimuli-session (approximately 14min), and 150 stimuli-session (20min) for each of the four groups, respectively. Therefore, the outcome will be measured with the spontaneous motor unit potentials (sMUPs) in the contralateral abductor pollicis brevis muscle (APB). After the stimulation session, we will measure sMUPs continuously for another 20min to observe the prolonged effect of the TRPMS stimulation and to compare these four conditions. The total approximate time required for this experiment is about 2-2.5 hours.

Group III: TMS-fMRI Experiment 1 Experimental Treatment 2 Interventions

To evaluate the relationship between BOLD activation and MEP and establish a BOLD activation marker of cortical excitability. Participants will start with a set of two short task-based EPI scans and anatomical scan. RMT will then be determined. Participants will undergo a single-pulse TMS-fMRI scan with stimulation intensities relative to the RMT over the motor cortex and/or the DLPFC. In total, six (6) intensities will be tested, 80% 100%, 105%, 110%, 115%, and 120% relative to the RMT. The fMRI design will be event-related. Each intensity (event type) will be presented 50 times. The order of the intensities will be randomized, and the inter-stimulus-interval (ISI) will range from 12s to 20s (centered at 16s plus random jittering in between, about 0.06Hz). The highest intensity of stimulation will be 120% RMT. EMG recordings in the corresponding hand muscle will be simultaneously acquired during the scan. Total approximate time required for this experiment is about 6-8 hours.

Group IV: MR Methodology Development and Evaluation Experimental Treatment 2 Interventions

Methodology development and evaluation consists of pulse sequence development, testing, and parameter optimization. For each method we develop or evaluate, we may recruit up to 40 participants to come in for up to 4 visits each. Each participant will be scanned for up to 2 sessions per visit, not to exceed 4 total scan hours per visit.

Magnetom Prisma Fit 3T Scanner is already approved in European Union, United States, Canada, Japan, China for the following indications:

Approved in European Union as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

Approved in United States as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

Approved in Canada as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

Approved in Japan as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

Approved in China as Magnetom Prisma Fit 3T Scanner for:

• General diagnostic imaging
• Neurological imaging
• Cardiovascular imaging

Who Is Running the Clinical Trial?

National Institute on Drug Abuse (NIDA)

Lead Sponsor

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

The Psychonaut 2002 project aims to develop a web-based tool that provides professionals with up-to-date information on drug-related disorders, focusing on evolving drug scenarios.

Preliminary results indicate that the tool can successfully identify emerging trends related to MDMA and similar substances, which can aid in prevention and intervention strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Importance of cyberspace for the assessment of the drug abuse market: preliminary results from the Psychonaut 2002 project. Schifano, F., Leoni, M., Martinotti, G., et al.[2019]

Recent advancements in imaging technologies, particularly PET and SPECT, have significantly enhanced our understanding of addiction as a brain disease by allowing direct observation of drug effects in human users.

These imaging techniques have integrated with biochemistry and pharmacology to measure how drugs of abuse impact the brain, highlighting the extensive medical and social consequences of addiction across various medical fields.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Positron emission tomography and single-photon emission computed tomography in substance abuse research. Volkow, ND., Fowler, JS., Wang, GJ.[2019]

The National Electrical Manufacturers Association (NEMA) issued recommendations to ensure the safety and compatibility of third-party accessories used with MRI equipment, addressing potential interactions and hazards in the MR scanning environment.

These guidelines are based on input from MR system manufacturers and aim to improve the design and testing of MR accessories, ensuring they do not pose safety risks to patients and staff during scans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accessory equipment considerations with respect to MRI compatibility. Keeler, EK., Casey, FX., Engels, H., et al.[2019]

The study found that implanted neurostimulators can experience significant voltage output changes in magnetic resonance (MR) imagers, with outputs reaching up to 12V in some cases, which can cause discomfort or harm to patients, as typical therapeutic values are only 1-5V.

Certain self-powered neurostimulators, like the Medtronic Itrel and Cordis MK II, were not affected in their programmed stimulus parameters by the MR fields, but the RF fields could heat their metal cases, indicating that while some devices can be scanned safely, caution is needed depending on the type of neurostimulator.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of magnetic resonance imagers on implanted neurostimulators. Gleason, CA., Kaula, NF., Hricak, H., et al.[2019]

MRI has been instrumental in addiction research, revealing disturbances in frontostriatal circuitry that are linked to cognitive functions predicting drug relapse and treatment responses.

Future advancements in MRI technology, such as increased field strength, promise to enhance image quality and deepen our understanding of brain structure and function in relation to addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neurobiology of addiction: the perspective from magnetic resonance imaging present and future. Suckling, J., Nestor, LJ.[2022]

The Internet can significantly enhance addiction treatment by enabling efficient delivery of educational content and secure collection of self-reported data on substance use, making treatment more accessible and effective.

Internet applications support various aspects of addiction treatment, including assessment, monitoring patient outcomes, ongoing recovery support, and training for treatment providers, ultimately improving the quality of care and patient engagement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How Internet technology can improve the quality of care for substance use disorders. Cucciare, MA., Weingardt, KR., Humphreys, K.[2019]

This study measured occupational exposure levels to gradient magnetic fields (GMF) from 1.5 and 3.0 Tesla MRI scanners using a specialized probe, focusing on the weighed peak (WP) method recommended by the ICNIRP.

The results showed that the measured WP values were within the safety limits set by ICNIRP for occupational exposure, indicating that working near these MRI scanners is compliant with safety standards.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measurement of the weighted peak level for occupational exposure to gradient magnetic fields for 1.5 and 3 Tesla MRI body scanners. Bonutti, F., Tecchio, M., Maieron, M., et al.[2016]

The study explores the effectiveness of a controlled drinking computer program designed for individuals with drinking problems, particularly targeting drink driving offenders.

This approach suggests that using microcomputer programs could be a cost-effective and efficient treatment option for addressing alcohol-related issues, leveraging the positive evidence for brief interventions and self-help materials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can microcomputers help the problem drinker? Eltringham, A., Barber, JG.[2006]

In a study involving 14 patients with various cardiac devices, all 16 MRI scans at 3T were completed successfully without any arrhythmias or significant changes in device parameters, indicating that 3T MRI can be safely performed on cardiac device patients with proper precautions.

The study highlights the importance of careful device reprogramming and extensive monitoring during the MRI process, allowing for safe imaging while minimizing risks associated with the magnetic field.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance imaging of implantable cardiac rhythm devices at 3.0 tesla. Gimbel, JR.[2008]

Recent advances in neuroimaging techniques like MRI and PET have significantly improved our understanding of drug addiction as a brain disorder, revealing how behavioral traits and environmental factors interact with neural changes from drug abuse.

The review highlights the role of impulsivity and sensation-seeking traits in increasing the risk of developing compulsive drug use and relapse, with consistent imaging findings across studies in rats, monkeys, and humans, particularly related to dopamine neurotransmission.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Behavioral endophenotypes of drug addiction: Etiological insights from neuroimaging studies. Jupp, B., Dalley, JW.[2022]

Recent advancements in opioid imaging, particularly with high-resolution PET scanners and new radioligands, have significantly enhanced research in pain, addiction, and epilepsy.

The future of opioid imaging looks promising, with expectations for broader clinical applications and impacts as PET technology becomes more accessible, potentially improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opioid imaging. Hammers, A., Lingford-Hughes, A.[2022]

SPECT and PET imaging techniques have become essential tools in understanding the neurochemical and physiological changes in the brain during recovery from addiction, allowing researchers to study individuals at various stages of abstinence.

These imaging modalities have provided insights into the pharmacokinetics and pharmacodynamics of abused drugs, revealing important information about drug mechanisms, interactions, and toxicities, and have been effectively combined with neuropsychological testing to correlate brain activity with human experiences like euphoria and craving.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PET imaging in clinical drug abuse research. Gatley, SJ., Volkow, ND., Wang, GJ., et al.[2019]

A survey of 120 outpatients revealed that only 50-55% were asked about the presence of a pacemaker during MRI referrals, highlighting a significant gap in safety protocols that could lead to near-misses with MRI-unsafe devices.

Following the survey, several interventions were implemented, resulting in improved patient safety with no recorded near-misses over the next 12 months, suggesting that better communication and education about MRI safety can effectively reduce risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developing patient-centred MRI safety culture: a quality improvement report. Yong, A., Kanodia, AK., Wendy, M., et al.[2022]

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MagVenture TMS Machines MagVenture TMS Therapy™ system has been FDA-cleared to treat Major Depressive Disorder (MDD) with comorbid anxiety symptoms in adults. This allows providers to ...