Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging

Nicotine Dependence Clinical Trial

Official title:

Advanced Functional and Structural MRI Techniques for Neuropharmacological Imaging

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01036581
• Other study ID #: 999903380
• Secondary ID: 03-DA-N380
• Status: Recruiting
• Phase: N/A
• Start date: October 24, 2003
• Est. completion date: December 31, 2029

Study information

• Verified date: January 22, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: NIDA IRP Screening Team
• Phone: (800) 535-8254
• Email: researchstudies[@]nida.nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

• Functional and structural magnetic resonance imaging (MRI) techniques have allowed researchers to map and study how the brain works when at rest and when engaged in specific tasks. MRI scans have provided more information about how drugs affect the brain, and about how drug addiction changes the brain and influences behavior, mood, and thinking processes. To better understand the underlying mechanism of drug addiction and to develop strategies for more effective treatment, researchers are interested in developing new MRI techniques to study the effects of addiction on the brain.

Objectives:

• To develop new functional and structural MRI techniques, and to evaluate their potential use in brain imaging studies related to addiction.

Eligibility:

• Individuals between 18 and 80 years of age.

• Participants may be smokers or nonsmokers, and may use drugs or not use drugs.

Design:

• During the initial screening, participants will complete questionnaires about family and personal history, drug use, and other information as required by the researchers. Participants who will be asked to complete tasks during the MRI scan will be shown how to perform these tasks before the scanning session.

• Before each study session, participants may be asked to complete some or all of the following: questions about their drug use during the last week, a breathalyzer test, a urine drug-use assessment, a urine pregnancy test, or a measure of carbon monoxide. Participants will also provide blood samples before the start of the scan.

• For each scanning session, participants will have an MRI scan that will last approximately 2 hours.

• MRI scans may include specific tasks to be performed during the scan, or an experiment that studies the brain's response to carbon dioxide.

Description:

Objective:

Functional and structural magnetic resonance imaging techniques have proven essential for noninvasive mapping of brain physiology and pathology. The primary objective of this protocol is to develop advanced magnetic resonance imaging and spectroscopy (MRI and MRS) techniques for neuroimaging studies related to addiction. These neuroimaging techniques will be used in other studies to better understand the underlying mechanism of drug addiction and to potentially develop strategies for more effective treatment.

Study population:

Healthy controls and drug users will participate in the study. Technical developments of MRI/MRS will be performed on healthy controls, while the evaluation of the applicability of these techniques to addiction related neuroimaging studies will be performed using drug users and healthy controls.

Design:

Based on the fundamental principle of the biophysical transduction of physiological signals to magnetic resonance (MR) imaging and spectroscopic signals, advanced techniques will be developed to measure the activity, metabolism, structure, and biochemistry of the brain. The development of these techniques typically includes the following steps: 1) proof-of-concept computer simulations, 2) implementation of the imaging concept with an MRI scanner and phantoms, 3) feasibility testing on control subjects, and 4) evaluation of the sensitivity and specificity of these techniques in detecting functional changes modulated by task performance, CO2 (5%)administration, or non-invasive neuromodulation techniques (e.g.: transcranial magnetic stimulation (TMS), and transcranial rotating permanent magnet stimulation (TRPMS), 5) evaluation of these techniques in detecting functional and/or structural alterations of the brain related to a specific disease.

Outcome measures:

Advanced neuroimaging techniques developed from this protocol will demonstrate the ability to distinguish between drug using and control populations. Successful techniques will then be incorporated into hypothesis driven studies in the Neuroimaging Research Branch at NIDA-IRP. These techniques will also be useful, through publications and technology transfer, to the entire neuroimaging society.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 750
• Est. completion date: December 31, 2029
• Est. primary completion date: December 31, 2029
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

• Subjects must be between the ages of 18-80, be generally healthy and male or non-pregnant female. Smokers, non-smokers, drug using and non-drug using populations will participate in this study.

INCLUSION CRITERIA:

General:

• Male and non-pregnant female adults between the ages of 18-80.

• All subjects must be able to provide informed consent.

EXCLUSION CRITERIA:

Subjects will be excluded if they:

• Are pregnant. Urine pregnancy tests will be performed on all female volunteers of child-bearing potential before each experimental session.

• Are unable to undergo MRI scanning due to implanted metallic devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts including Copper 7 IUD) or claustrophobia.

• Have major medical illnesses severe enough to impact data being gathered, to include, but not limited to, hypertension, cardiovascular disease, asthma, diabetes, peripheral vascular diseases, coagulopathies, syncope, history of superficial or deep vein thrombosis, HIV, or other clinically significant infectious diseases that may alter the signal being measured.

• Have current major psychiatric disorders to include, but not limited to, mood, anxiety, psychotic disorders.

• Have neurological illnesses severe enough to impact data being gathered, including, but not limited to, seizure disorders, migraine, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS tumor.

• Are non-English speaking. Justification: There is no direct benefit to participants in this study, and some of the study procedures involve more than minimal risk. To include non-English speakers, we would have to translate the consent and other study documents and hire and train bilingual staff, which would require resources that we do not have and could not justify given the small sample size for each experiment. Additionally, the data integrity of some of the cognitive tasks and standardized questionnaires used in this study would be compromised as they have only been validated in English. Most importantly, ongoing communication regarding safety procedures is necessary when participants are undergoing MRI and TMS/TRPMS procedures. The inability to effectively communicate MRI and TMS/TRPMS safety procedures could compromise the safety of non-English speaking participants.

• Suspected or confirmed active SARS-CoV-2 infection. Assessment tool: 2019 Novel Coronavirus (COVID-19) patient screening tool administered by phone prior to participant arrival. The current version of the screening tool to be used is available at http://intranet.cc.nih.gov/hospitalepidemiology/emerging_infectious_diseases.html). Viral testing looking for SARS-CoV-2 in a specimen deemed appropriate by NIH (such as nasopharyngeal or mid-turbinate swab) may also be completed. We reserve the right to change the specimen type as NIH approves new test procedures. This test may be carried out in-house at NIDA, NIH, at a community testing site or through a commercial vendor. Anyone with a positive symptom screen without a clear alternative explanation or a positive viral test will be excluded until they recover or (for asymptomatic cases) are no longer infectious. MAI will also retain the ability to exclude for a suspicious symptom screen without positive viral test. Justification: COVID-19 is extremely infectious and can have serious consequences. Allowing participants with active infection would alter the risk:benefit ratio for non-treatment studies without a primary focus on SARS-CoV-2 to an unacceptable level of risk. In addition, COVID-19 can have cognitive consequences which would add unnecessary noise to the study data. Testing will continue as long as public health officials and/or NIDA medical personnel deem it appropriate.

Subjects to be considered for Non-Invasive Brain Stimulation (NIBS) will also be excluded if they:

1. Are unable to safely undergo a NIBS procedure due to having epilepsy or being at high risk for a seizure, being sleep deprived, having a history of unexplained fainting, recurrent severe headaches, significant head injury, having undergone a neurosurgical procedure, having metal in the head, having hearing problems or ringing in the ears or implanted medical devices that could malfunction under NIBS.

Additional characterization information will be gathered during screening for some experiments. As this protocol is to develop imaging techniques, this information will be gathered as needed, depending on the phase of development and specific technique requirements, but are not I/E criteria:

Based on the scientific and medical requirements of the particular experiment, participants may also be assessed for:

1. age (Some experiments may want to target a particular age range. For example, cognitive tasks generally exclude participants over 60, an age when cognitive issues tend to become more commonplace)

2. left-handedness (if desired for a particular task),

3. color-blindness (if using a task requiring color discrimination),

4. drug use diagnosis

5. use of psychoactive or vascularly active medications (if a functional fMRI technique that is sensitive to hemodynamic changes is being used).

6. cognitive impairment as assessed by full scale IQ of 80 measured by the WASI or Shipley-2. Justification: Cognitive impairment and learning disabilities are associated with alterations in brain regions used to accomplish tasks, and, therefore, may introduce significant variably into the data.

Related Conditions & MeSH terms

• Drug Abuse
• Nicotine Dependence
• Substance-Related Disorders
• Tobacco Use Disorder

Intervention

Device:
• MagPro X100 Magnetic Stimulator
Concurrent TMS-MRI acquisition allows us to investigate the acute effects of induced brain activity on BOLD signal and evaluate interference of the TMS pulse with the BOLD signal measurement.
• Transcranial Rotating Magnetic Stimulator
Participants will undergo transcranial rapid rotating permanent magnetic stimulation (TRPMS), with the aim of evaluating the prolonged effect of TRPMS on motor cortex excitability. In another experiment, participants will undergo TRPMS with the aim of evaluating cortical excitability changes with TRPMS. These experiments will help interpret subsequent experiments investigating the effect of TRPMS on BOLD signal.
• Magnetom Prisma Fit 3T Scanner
Type: MRI Name: Magnetom Prisma Fit 3T Scanner (Siemens) Description: Functional and structural magnetic resonance imaging techniques are used for noninvasive mapping of brain physiology and pathology and to develop advanced magnetic resonance imaging and spectroscopy (MRI and MRS) techniques for neuroimaging studies related to addiction.

Locations

Country	Name	City	State
United States	National Institute on Drug Abuse, Biomedical Research Center (BRC)	Baltimore	Maryland
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To develop a simultaneous perfusion and BOLD imaging technique with improved functional contrasts and reduced susceptibility artifacts for determination of CMRO2 during brain activation	perfusion/BOLD imaging data	at each visit
Primary	To develop efficient methods to reduce image artifacts caused by susceptibility-induced field inhomogeneity and head motion, and therefore to improve reliability and sensitivity of functional imaging	MRI scan data	at each visit
Primary	To develop an imaging technique to identify fiber crossing in the brain based on high-angular resolution measurements of apparent diffusion coefficient (ADC), and subsequently to develop improved fiber tracking techniques to delineate neuronal p...	MRI scan data	at each visit
Primary	To develop MRS techniques that are able to reliably measure metabolite and neurotransmitter concentrations in the brain at 3 Tesla, and to evaluate their feasibility and efficacy in drug addiction studies	MRS data from MRI scans	at each visit
Primary	To integrate genetic analysis with morphological and functional measurement of the amygdala, hippocampus, and other regions, which may help to account for some of the noise in these measurements	MRI scan data and blood samples collected in 380 or 457 (NRB genetics protocol).	at each visit
Primary	To assess effects of neuromodulation techniques, such as TMS and TRPMS, on brain activity and relevant MRI signals	MRI scan data; spontaneous motor unit potentials (sMUPs) in the contralateral abductor pollicis brevis muscle (APB)	at each visit