Development Of Neuroimaging Methods To Assess The Neurobiology Of Addiction

Normal Physiology Clinical Trial

Official title:

Development of Neuroimaging Methods to Assess the Neurobiology of Addiction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02535702
• Other study ID #: 150186
• Secondary ID: 15-AA-0186
• Status: Recruiting
• Phase: N/A
• Start date: June 28, 2016
• Est. completion date: December 31, 2026

Study information

• Verified date: February 22, 2024
• Source: National Institutes of Health Clinical Center (CC)
• Contact: Dardo G Tomasi, Ph.D.
• Phone: (301) 496-1589
• Email: dardo.tomasi[@]nih.gov
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Background:

Abusing alcohol, drugs, and other substances can cause serious health problems. These substances also can affect brain function. Researchers want to learn more about brain function by using magnetic resonance imaging (MRI). This uses a magnetic field and radio waves to take pictures of the brain.

Objective:

To develop new ways to use MRI to study the brain.

Eligibility:

Healthy people 18 years of age or older.

Design:

Participants will be screened with a medical history, physical exam, and blood and urine tests.

They will answer questions about their drug use and psychiatric history. They will be asked about family history of alcoholism or drug abuse.

Participants will answer questions to see if they can participate in MRI.

Participants will have MRI scans. The scanner is a metal cylinder in a strong magnetic field. Participants will lie on a table that slides in and out of the cylinder. A device called a coil may be placed over the head.

Each sub-study will include up to 3 different MRI visits. Participants can be in multiple sub-studies. But they can have only 1 MRI per week and 20 per year.

During MRI visits, participants may have urine collected. They may get another MRI questionnaire.

Participants may have a clinical MRI brain scan. This may show physical problems in the brain.

During some scans, participants may perform simple movement, memory, and thinking tasks.

Participants may be connected to a machine to monitor brain activity during the scan. Small metal electrodes will be placed on the scalp. A gel will be placed in the space between the electrodes and the scalp.

Description:

• Objectives: To improve sensitivity as well as spectral and spatiotemporal resolutions in magnetic resonance (MR) studies assessing structural, neurochemical, hemodynamic and electrophysiological changes that occur in the human brain during the resting state as well as those that occur in response to novel sensory, motor, cognitive or emotional stimulation paradigms.

• Study population: We intend to complete studies in 128 healthy volunteers, (64 males and 64 females, 18 years or older).

• Design: We will conduct pilot studies, each with up to 16 subjects, to optimize MR pulse sequences and/or functional MR imaging (fMRI) task paradigms pertinent to the theme of Addiction . MR pulse sequences and/or fMRI task paradigms will be validated against

appropriated gold-standard methods/tasks. These studies are required to maximize the sensitivity of new imaging techniques and fMRI tasks used for clinical and research applications that take advantage of 3T MRI scanners at NIH. If an exploratory study leads to results of interest, and if a larger population is necessary to reach statistical significance, a separate protocol will be submitted with a priori hypotheses, specific study design and power analysis adapted from the pilot studies performed in the present protocol.

• Outcome parameters: Although multiple measures will be collected, the primary outcome will be amplitude and reliability of regional-specific BOLD fMRI signals.

• MRI: we will analyze measures such as the amplitude and the reliability of the test-retest measures of fMRI signals; functional connectivity metrics; tractography between seed and target regions of interest (diffusion tensor imaging, DTI); brain morphometry (using

automatic segmentation and voxel-brain morphometry, VBM); and brain metabolite levels in regions of interest (using MR spectroscopy, MRS).

• EEG (electroencephalography): we will quantify measures such as event or task-related potentials, and coherence between sensors or sources located close to the brain areas of interest.

• Behavioral measures: during fMRI we will quantify measures such as reaction times and accuracy (using MRI compatible response pads) as well as eye movement (using MRI compatible eye trackers) and self-reports of the study experience (i.e., degree of interest

and motivation and alertness).

-Physiological measures: During fMRI, we will record physiological parameters such as blood pressure, skin conductance, respiratory frequency, or heart rate, to interpret outcome measures.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 192
• Est. completion date: December 31, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

• INCLUSION CRITERIA:

1. Eighteen years or older.

2. Ability to provide written informed consent as determined by physical examination and verbal communication. Capacity to consent will be determined by those obtaining the informed consent.

3. Willingness to abstain from drug use on scheduled testing days.

EXCLUSION CRITERIA

1. Positive urine pregnancy test in females.

2. Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head (including but not limited to pacemakers or other implanted electrical devices, brain stimulators, some types of dental implants, aneurysm clips, metallic prostheses, permanent eyeliner, implanted delivery pump, or shrapnel fragments) or fear of enclosed spaces as determined by the self-report checklist.

3. Claustrophobia.

4. Body weight >550 lbs, which is the weight limit of the MR scanner.

5. Current DSM-5 diagnosis of a psychiatric disorder (other than nicotine/caffeine use disorders) as determined by history and clinical exam including substance use disorder, alcoholism and alcohol dependence. Past history of a mental disorder as defined by DSM-IV or DSM-5 will be excluded only if it was severe enough as to require hospitalization (any length), or chronic medication management (more than 4 weeks), or that could impact brain function at the time of the study. Subjects receiving psychotherapy may be included in the study.

6. Those with a binge drinking history every month continuously for the last 10 years will also be excluded. Binge drinkers are those who being female consume 4 or more drinks and males consume 5 or more drinks in one occasion at least once a month.

7. Serious neurological disorder such as MS, Parkinson s Disease, ALS, sensory loss or peripheral neuropathy.

8. Currently taking any psychoactive drugs such as Celexa (TM), Prozac (TM), Wellbutrin (TM), Zoloft (TM), and/or stimulants other than caffeine such as Adderall (TM), Dexedrine (TM) and Ritalin (TM). Subjects taking PRN medications (e.g., sleep medications) may be included in the study.

9. Clinically significant laboratory or examination results.

10. Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).

11. *Non-English speakers (must also be able to read and comprehend English).

• The intent of the research has no prospect of direct benefit to the subject. Therefore, we are excluding non-English speakers in this research study since our fMRI paradigms (particularly the Delay Discounting task) require that the subject be able to speak, read and comprehend English.

Subjects will not be excluded from enrollment onto this study if their urine test or breath alcohol level (BAL) is positive for drugs/alcohol on initial screening. However, if they test positive on scheduled study procedure days involving MRI, the procedures will be postponed and rescheduled. We will allow for up to 3 rescheduled study days that were the result of positive urine drug or BAL screens. If the drug/BAL tests is/are positive on the third rescheduled visit, the participant will be withdrawn from the study.

Related Conditions & MeSH terms

• Behavior, Addictive
• Normal Physiology

Intervention

Other:
• In vivo MRS
1H MR spectroscopy to assess brain metabolites.
• fMRI
Three fMRI sessions to assess test-retest reliability of functional connectivity (FC) measures at rest and during task performance.
• EEG/EOG
Electroencephalography or electrooculography (EEG/ EOG) sessions to record electrical activity of the brain or measure corneo-retinal standing potentials.
• Stimulation tasks
To be used in the context of fMRI to study blood-oxygenation-level- dependent responses in the brain to sensory stimulation.
• NSPRD
To be used in conjunction with pupillometry in the context of fMRI to study blood-oxygenation-level-dependent responses to selective neurostimulation of pain fibers.
• Structural MRI
High spatial MRI and diffusion tensor imaging (DTI) to assess brain morphology and structural connectivity.

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Country where clinical trial is conducted

United States, 

References & Publications (3)

Tomasi D, Caparelli EC, Chang L, Ernst T. fMRI-acoustic noise alters brain activation during working memory tasks. Neuroimage. 2005 Aug 15;27(2):377-86. doi: 10.1016/j.neuroimage.2005.04.010. — View Citation

Tomasi D, Wang GJ, Studentsova Y, Volkow ND. Dissecting Neural Responses to Temporal Prediction, Attention, and Memory: Effects of Reward Learning and Interoception on Time Perception. Cereb Cortex. 2015 Oct;25(10):3856-67. doi: 10.1093/cercor/bhu269. Epub 2014 Nov 11. — View Citation

Tomasi D, Wang R, Wang GJ, Volkow ND. Functional connectivity and brain activation: a synergistic approach. Cereb Cortex. 2014 Oct;24(10):2619-29. doi: 10.1093/cercor/bht119. Epub 2013 May 3. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary outcome will be amplitude and reliability of regional-specific BOLD fMRI signals.	MRI: we will analyze measures such as the amplitude and the reliability of the test-retest measures of fMRI signals; functional connectivity metrics; tractography between seed and target regions of interest (diffusion tensor imaging, DTI); morphometry of brain regions (using automatic segmentation and voxel-brain morphometry, VBM); and brain metabolite levels in regions of interest (using MR spectroscopy, MRS).	end of study
Primary	The primary outcome will be amplitude and reliability of regional-specific BOLD fMRI signals.	EEG (electroencephalography): we will quantify measures such as event or task-related potentials, and coherence between sensors or sources located close to the brain areas of interest. We are also quantifying blink rates from the electrooculogram (EOG).	end of study
Primary	The primary outcome will be amplitude and reliability of regional-specific BOLD fMRI signals.	Behavioral measures during fMRI tasks: we will quantify measures such as reaction times and accuracy (using MRI compatible response pads) as well as eye movement (using MRI compatible eye trackers) and self-reports of the study experience (i.e. degree of interest and motivation and alertness).	end of study
Secondary	Collection of autonomic data	Autonomic data may be collected or observations made during the course of the experiment that will give further information about the state of the body and emotions during experiments (blood pressure, skin conductance, respiratory rate). Self-report data may be collected during the course of the experiment to assess the level of interest, boredom, alertness of the participants.	end of study

External Links

•   NIH Clinical Center Detailed Web Page