Dopaminergic Modulation of Brain Activation Using Simultaneous PET/Pharmacological MRI
Condition: Normal Physiology
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Oral Methylphenidate followed by IV placebo; Oral placebo followed by IV Methylphenidate; Oral Placebo followed by IV Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Oral MP (60 mg) will be given 30 minutes prior to bolus [11C]raclopride injection followed by iv placebo (PL) given 30 minutes post bolus injection of [11C]raclopride.; Oral PL will be given 30 minutes prior to bolus [11C]raclopride injection followed by iv MP (0.25 mg/kg) given 30 minutes post bolus injection of [11C]raclopride.; Oral PL will be given 30 minutes prior to bolus [11C]raclopride injection followed by iv PL given 30 minutes post bolus injection of [11C]raclopride.
Intervention MeSH terms: Methylphenidate
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Pharmacological MRI; C-11 Raclopride; PET Imaging; Neuropsychological Testing