NCT02233829

Dopamine Rhythms in Health and Addiction

• Status: Withdrawn
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: National Institute on Alcohol Abuse and Alcoholism (NIAAA) · NIH
• Sex: All
• Age: 21 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

Background: \- Dopamine is a chemical signal linked to the rewarding effects of drugs. Certain genes make these effects sensitive to the time of day they are taken. Cocaine can affect these genes in the brain. Researchers want to measure brain dopamine at different times of day. Objectives: \- To look for changes to a person s biological clock in the function of the dopamine reward system. To test if cocaine disrupts this. Eligibility: * Adults age 21-55 with a cocaine use disorder. * Healthy volunteers age 21-55. Design: * Participants will be screened with medical history, physical exam, interview, and blood and urine tests. Their breath will be tested for alcohol and recent smoking. * Participants will have 3 overnight clinic visits. * Visit 1: They will have blood and urine collected and a heart test. * A plastic tube (catheter) will be placed into a vein in each arm by needle. * Participants will have a PET scan in a donut-shaped machine. They will lie on a bed that slides in and out of it, wearing a cap. A radiotracer (measures dopamine) and a drug (blocks dopamine removal) will be injected via catheter. Vital signs will be measured and blood will be drawn throughout. * Visit 2: repeats Visit 1, except at night. * Visit 3, participants will have urine collected. * They will have MRI scans in a metal cylinder surrounded by a magnetic field. They will lie on a table that slides in and out of it, with a coil over their head. * Participants may answer questions, take computer or paper tests, and perform simple actions. * For 1 week, participants will wear a wrist device that measures daily activity.

Detailed description

Objectives: The primary objective is to assess if there is disruption of circadian DA rhythms in cocaine addiction. The secondary objective is to assess if dopamine modulates the sensitivity of the brain reward network in a circadian dependent manner. Study Population: Non-treatment seeking cocaine abusers (moderate or severe cocaine use disorder as per DSM-IV or DSM 5) and healthy controls. Males and females will be included. Design: Participants will undergo two PET scans with \[11C\]raclopride using a bolus infusion paradigm to assess baseline D2R availability followed by an infusion to assess changes in DA as measured by \[11C\]raclopride s displacement following an intravenous injection of methylphenidate (MP). They will also undergo a total of 4 MRI scans, two after placebo and two after MP to assess the circadian variations in the sensitivity of the brain reward network. The two \[11C\]raclopride scans will be done on separate days at least one week apart, one in the morning starting between (7-9 AM) and one in the early evening (5-7 PM) and they will be followed by an MRI scan to assess the sensitivity of the brain reward network under the influence of MP in the morning (9-11AM) and in the evening (7-9 PM). For the Placebo MRI scans participants will be tested either on separate days or on the morning of the evening session or on the evening prior to the morning session. We will use the MRI scans to assess the sensitivity of the brain reward circuit to visual presentation of drug or food cues and to evaluate resting functional connectivity. Outcome Parameters: Main outcome measure is to assess if there are differences in DA release between the morning and the evening (displacement of \[11C\]raclopride binding after MP) and to determine if these diurnal patterns differ in cocaine addiction. Secondary outcome measures are: To assess if DA signaling correlates with reactivity of brain regions to exposure of food and drug cues and with functional connectivity of the reward network and to assess if the reactivity of the reward network shows circadian variability. We will also assess if differences in DA signaling between morning and evening correlate with circadian typology and with measures of spontaneous motor activity and with sleeping patterns.

Conditions

• Cocaine Abuse

Interventions

Type	Name	Description
DRUG	Brain Dopamine Reactivity	IV methylphenidate, used under IND #124, 912 is injected into the subject s bloodstream to be used in conjunction with PET imaging to show displacement of \[11C\]raclopride.
RADIATION	Brain Dopamine Receptor	The radiotracer \[11C\] raclopride is used for imaging dopamine receptors and dopamine release.

Timeline

• Start date: 2024-04-23
• Primary completion: 2024-04-23
• Completion: 2024-04-23
• First posted: 2014-09-09
• Last updated: 2024-04-24

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study