Dopamine Rhythms in Health and Addiction

NCT02233829 | Withdrawn Early Phase 1 FDA Drug

• 2 other identifiers: 14018714-AA-0187
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cocaine Abuse

Keywords

C-11 Raclopride; PET; Circadian Rhythm

Outcome Measures

Primary Outcomes (1)

• To determine if there is disruption in circadian rhythms in cocaine use disorder (CUD) as compared to healthy controls.

  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.

  end of study

Secondary Outcomes (3)

• Measuring dopamine signaling

  end of study

• Measuring circadian typology

  end of study

• Measuring sleep patterns

  end of study

Study Arms (2)

Evening MRI/PET/Raclopride/IV Methylphenidate Session

ACTIVE COMPARATOR

The PET \[11C\] raclopride scan will be done between 5-7 PM. After iv catheters are inserted blood sampling starts and continues throughout study. Cardiac monitoring is initiated and continues until physician discontinues post PET scan. Bolus-plus-infusion method for \[11C\]raclopride and the administration of intravenous MP (0.5 mg/kg) forty-five minutes after initial bolus injection of \[11C\]raclopride. Scan to be done for a total of 100 minutes.

Drug: Brain Dopamine Reactivity; Radiation: Brain Dopamine Receptor

Morning MRI/PET/Raclopride/IV Methylphenidate Session

ACTIVE COMPARATOR

Morning Session \[11C\]raclopride PET scan: To be started between 7-8 AM. After iv catheters are inserted, genetic blood samples are drawn and then blood sampling starts and continues throughout study. Cardiac monitoring is initiated and continues until physician discontinues post PET scan. Bolus-plusinfusion method for \[11C\]raclopride and the administration of intravenous MP (0.25 mg/kg) fortyfive minutes after initial bolus injection of \[11C\]raclopride. Scan to be done for a total of 100 minutes.

Drug: Brain Dopamine Reactivity; Radiation: Brain Dopamine Receptor

Interventions

Brain Dopamine Reactivity DRUG

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.

Evening MRI/PET/Raclopride/IV Methylphenidate Session; Morning MRI/PET/Raclopride/IV Methylphenidate Session

Brain Dopamine Receptor RADIATION

The radiotracer \[11C\] raclopride is used for imaging dopamine receptors and dopamine release.

Evening MRI/PET/Raclopride/IV Methylphenidate Session; Morning MRI/PET/Raclopride/IV Methylphenidate Session

Eligibility Criteria

• Age: 21 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Between 21 and 55 years of age.
• Ability to provide written informed consent.
• DSM-IV or DSM-5 diagnosis of a moderate or severe cocaine use disorder established through history and clinical exam.
• Non-treatment seeking cocaine users (actively consuming cocaine - last use within one week of study as assessed by self-reports).
• Minimum 10 years history of cocaine abuse predominantly via smoking or injection - self-report.
• Must consume at least 4 grams of cocaine per week - self-report.

You may not qualify if:

• Current or past DSM-IV or DSM-5 diagnosis of a psychiatric disorder (other than cocaine for the cocaine abusers, and nicotine/caffeine for any of the participants) that required hospitalization (any length), or chronic medication management (more than 4 weeks) and that could impact brain function at the time of the study as determined by history and clinical exam.
• Major medical problems that can permanently 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.
• 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.
• Head trauma with loss of consciousness for more than 30 minutes as determined by medical history and physical exam.
• 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.
• History of coagulation disorder as evidenced from clinical laboratory results, medical history.
• History of glaucoma as determined by medical history. Since glaucoma is screened for clinically at about the age of 40, any subjects 40 or older will undergo a glaucoma screening test if they have not been tested by their primary care physician. A result of 21 mmHg or higher will exclude.
• 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.
• Personal or family history for cerebral aneurism.
• Past or present history of chest pain and trouble breathing with activity.
• Diabetes as assessed by medical history.
• Cannot lie comfortably flat on your back for up to 2 hours in the PET and MRI scanners - self-report.
• Weight \> 400 pounds which is the maximum weight the PET scanner can hold.
• Study investigators and staff, as well as their superiors, subordinates and immediate family members (adult children, spouses, parents, siblings).
• Note that subjects will not be excluded from enrollment onto this study if their urine test is positive for drugs on initial screening. The following guidelines will be followed for positive drug screens on study procedure days:

Sponsors & Collaborators

• National Institute on Alcohol Abuse and Alcoholism (NIAAA): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 10450679 BACKGROUND

• 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. doi: 10.1016/s0140-6736(00)03643-6.

  PMID: 11210998 BACKGROUND

• 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.

  PMID: 20362560 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Cocaine-Related Disorders

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Gene-Jack Wang, M.D.

  National Institute on Alcohol Abuse and Alcoholism (NIAAA)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2014
• First Posted: September 9, 2014
• Study Start: April 23, 2024
• Primary Completion: April 23, 2024
• Study Completion: April 23, 2024
• Last Updated: April 24, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)