Dopamine Rhythms in Health and Addiction
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Cocaine Abuse
Intervention: Brain Dopamine Reactivity (Drug); Brain Dopamine Receptor (Drug)
Phase: Phase 0
Status: Suspended
Sponsored by: National Institute on Alcohol Abuse and Alcoholism (NIAAA) Official(s) and/or principal investigator(s): Gene-Jack Wang, M.D., Principal Investigator, Affiliation: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
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.
Clinical Details
Official title: Dopamine Rhythms in Health and Addiction
Study design: Allocation: Non-Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science
Primary outcome: To assess if there are diurnal rhythms in DA signaling and in reward brain circuits and to determine if these are disrupted in cocaine addiction.
Secondary outcome: To determine if differences in measures of DA signaling between morning and evening correlate with circadian typology.To determine if measures of DA signaling correlate with measures of spontaneous motor activity and with sleeping patterns. To assess if DA signaling correlates with reactivity of brain regions to exposure of drug and with functional connectivity of the reward network and to assess if the reactivity of reward network shows circadian variability.
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) 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). The two [11C]raclopride scans will be done on separate days, one in
the morning starting between (7-9 AM) and one in the early evening (5-7 PM) with at least
one week between drug administrations. On a separate day we will perform MRI scans to
assess sensitivity of brain reward circuits to visual presentation of drug or food cues and
to evaluate resting functional connectivity and these measures will be obtained at three
time periods, 6-8 AM, 2-4 PM and 9-11 PM.
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.
Eligibility
Minimum age: 21 Years.
Maximum age: 55 Years.
Gender(s): Both.
Criteria:
- INCLUSION CRITERIA:
All Participants
1. Between 21 and 55 years of age.
2. Ability to provide written informed consent as determined by successful completion of
consent quiz prior to signing consent.
Inclusion Specific For Cocaine Use Disorder (CUD) Participants
1. DSM-IV diagnosis of a moderate or severe cocaine use disorder (established through
history and clinical exam).
2. Non-treatment seeking cocaine users (actively consuming cocaine - last use within one
week of study as assessed by self-reports).
3. Minimum 10 years history of cocaine abuse predominantly via smoking or injection -
self-report.
4. Must consume at least 4 grams of cocaine per week - self-report.
EXCLUSION CRITERIA:
All Participants
1. Use, in the past two weeks, of psychoactive medications (four weeks for fluoxetine)
or medications that may affect brain function (including but not limited to
meperidine, tricyclic antidpressants, selective serotonin reuptake inhibitors
(SSRIs), or serotonin norepinephrine reuptake inhibitors (SNRIs) as determined by
medical history and physical exam.
2. Current DSM-IV diagnosis of a psychiatric disorder (other than cocaine for the
cocaine abusers and nicotine for any of the participants) as determined by history
and clinical exam. Past history of a mental disorder as defined by DSM IV will be
excluded only if it was severe enough as to require treatment.
3. Current or previous chronic treatment (greater than 3 months) with stimulant
medications (amphetamine or methylphenidate).
4. Major medical problems that can impact brain function (e. g., CNS including seizures
and psychosis; cardiovascular including hypertension [BP > 140/90] and clinically
significant arrhythmias except bradycardia; metabolic, autoimmune, endocrine; +HIV)
as determined by history.
5. Any clinically significant laboratory finding as determined during the screening
procedures as evidenced from clinical laboratory results.
6. Have had previous radiation exposure (from X-rays, PET scans, or other exposure)
that, with the exposure from this study, would exceed NIH annual research limits as
determined by medical history and physical exam.
7. Head trauma with loss of consciousness for more than 30 minutes as determined by
medical history and physical exam;
8. Positive test for drugs on the day of the PET, the MRI or the NP tests as evidenced
from clinical laboratory results.
9. Pregnant or breast feeding: Females must have negative urine pregnancy test and are
not currently breastfeeding. Post-menopausal or surgically sterile (tubal ligation or
hysterectomy); or not sexually active with a male partner and able to get pregnant;
or documented agreement to use an effective form of birth control. Acceptable forms
of contraception include: hormonal contraceptives (birth-control pills, injectable
hormones, vaginal-ring hormones); IUD; diaphragm with spermicide; condom with
spermicide.
10. History of coagulation disorder as evidenced from clinical laboratory results,
medical history.
11. History of glaucoma as determined by medical history.
12. Presence of ferromagnetic objects in the body that are contraindicated for MRI of the
head (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 -
self-report checklist.
13. Cannot lie comfortably flat on your back for up to 2 hours in the PET and MRI
scanners self-report.
14. BMI > 30 or weight > 150 kilograms.
- Note: At any time a subject expresses that he/she wants to get treatment for
their cocaine use, we will immediately refer him/her to a treatment program. The
subject will be withdrawn from the study at that time.
Locations and Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States
Additional Information
NIH Clinical Center Detailed Web Page
Related publications: Wang GJ, Volkow ND, Fowler JS, Logan J, Pappas NR, Wong CT, Hitzemann RJ, Netusil N. Reproducibility of repeated measures of endogenous dopamine competition with [11C]raclopride in the human brain in response to methylphenidate. J Nucl Med. 1999 Aug;40(8):1285-91. Wang GJ, Volkow ND, Logan J, Pappas NR, Wong CT, Zhu W, Netusil N, Fowler JS. Brain dopamine and obesity. Lancet. 2001 Feb 3;357(9253):354-7. Dunn JP, Cowan RL, Volkow ND, Feurer ID, Li R, Williams DB, Kessler RM, Abumrad NN. Decreased dopamine type 2 receptor availability after bariatric surgery: preliminary findings. Brain Res. 2010 Sep 2;1350:123-30. doi: 10.1016/j.brainres.2010.03.064. Epub 2010 Mar 31.
Starting date: September 2014
Last updated: July 30, 2015
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