NCT03326245

Dopaminergic Modulation of Brain Activation Using Simultaneous PET/Pharmacological MRI

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) · NIH
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

Background: Dopamine (DA) is a chemical signal in the brain linked to learning, memory, and habits. Stimulant drugs like methylphenidate can increase DA in the brain. Researchers want to measure DA with and without this drug. They want to learn how methylphenidate and brain dopamine affect body responses, mood, and thinking. Objective: To better understand the role of dopamine in the brain and the effects of methylphenidate. Eligibility: Adults ages 18-55 who have used alcohol or stimulant drugs but have no drug dependence. Design: Participants will be screened with: * Physical exam * Question about medical, psychiatric, and alcohol and drug use history * Questions to see if it s safe to have a PET/MRI scan * Blood and urine tests * Breath test for alcohol Participants will have 3 or 4 study visits. At each visit they will have: * Urine and breath tested for alcohol and drugs * A thin plastic tube (catheter) inserted in each arm by needle * A small amount of radioactive chemical injected through the catheter. * PET/MRI scan. Participants will lie still on a table that slides in and out of a metal cylinder surrounded by a strong magnetic field. Their vital signs will be monitored. They will get earmuffs for loud noises. Before the scan, participants will get the study drug or placebo through the catheter. They may also get a sugar pill (placebo). They will get a small meal and have blood drawn. * Tests of memory, attention, and thinking. Participants will wear an activity monitor on the wrist for one week.

Detailed description

Objectives: The overarching goal of this study is to assess the dynamic association between dopamine (DA) D2 receptor (D2R) occupancy measured by positron emission tomography (PET) with \[11C\]raclopride and brain activity inferred by pharmacological magnetic resonance imaging (phMRI) in the human brain, and to assess the relative sensitivity and specificity of the neurovascular coupling for slow (oral) versus rapid (intravenous, IV) stimulant methylphenidate (MP) delivery. Secondary objectives are to assess the associations between behavioral measures (heart and respiration rates and blood pressure, motor and sleep parameters, and neuropsychological testing variables), D2R occupancy and fMRI signals. Study population: 10 healthy males and 10 healthy females 18-55 years old will be included. Test-retest reproducibility studies will be carried out in 5 participants. Design: Double-blind. Participants will undergo simultaneous PET/phMRI, to evaluate dynamic changes in D2R occupancy by DA with \[11C\]raclopride and in blood-oxygenation-level dependent (BOLD) signals, under MP or placebo (PL). The participants will be scanned on 3 different occasions: 1) oral-MP (60 mg) and iv PL (3 cc saline), 2) oral-PL and iv-MP (0.25 mg/kg in 3 cc sterile water) and 3) oral PL and iv PL, which will be carried in different study days with at least 48 hours between them and their order will be randomized across subjects. Participants and researchers will be blind to the nature of the stimulant drug (MP/PL). Outcome parameters: The scale factor between the distribution volume ratio (DVR) and the BOLD signal in the dorsal and ventral striatum for the slow and fast MP challenges.

Conditions

• Normal Physiology

Interventions

Type	Name	Description
DRUG	Methylphenidate Pill	Oral methylphenidate (60 mg) given 30 minutes prior to bolus \[11C\]raclopride
DRUG	Oral Placebo	Oral PL will be given 30 minutes prior to bolus \[11C\]raclopride injection
DRUG	Intravenous Placebo	Intravenous Placebo given 30 minutes post bolus injection of \[11C\]raclopride.
DRUG	Intravenous methylphenidate	Intravenous methylphenidate 0.25 mg/kg in 3ml sterile saline given 30 minutes post bolus injection of \[11C\]raclopride.

Timeline

• Start date: 2018-01-29
• Primary completion: 2021-12-13
• Completion: 2024-02-08
• First posted: 2017-10-31
• Last updated: 2024-05-28
• Results posted: 2024-05-28

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study