Brain Networks and Addiction Susceptibility

Completed · Phase 1

Conditions studied: Nicotine Dependence

In brief

Background: \- The risk for becoming addicted to drugs varies from person to person, even among those using similar drugs in a similar way. Researchers do not fully understand why some people become addicted to drugs and others do not. Studies suggest that under certain life circumstances, some genes may increase the risk for addiction. This study will use genetic information, computer tasks, magnetic resonance imaging (MRI), and other tests to see what brain networks may be related to drug addiction. Objectives: \- To better understand brain networks that may be related to susceptibility to drug addiction. Eligibility: \- Healthy non-smoking volunteers between 18 and 55 years of age. Design: * This study will have one screening visit and four all-day study visits. For male participants, the visits will be about 7 days apart over 5 to 7 weeks. Female participants will have the visits scheduled to coordinate with their menstrual cycle. * This study involves small doses of three approved drugs: two oral dopamine drugs and a nicotine patch. For each scanning session, participants will have three study drugs. However, only one pill or patch will be the real drug; the other two will be placebos. Some participants may have only placebos during a visit. * Participants will be screened with a physical exam and medical history. Blood and urine samples will be taken. Other tests will be given to ensure that participants are not smoking or using drugs while they are in the study. * During the all-day scanning visits, participants will receive two pills and one patch in the morning and they will be trained on simple computer tasks. In the afternoon, participants will have MRI scans and we will measure their brain activity while they rest and while they perform computer tasks in the scanner. Participants will also answer questionnaires during the scanning visits.

Key facts

Study ID

NCT01924468

Run by

National Institute on Drug Abuse (NIDA)

People needed

76

Starts

2013-08-14

Expected to finish

2019-05-14

Last updated by the study team

2019-05-16

Who can join

Age: 18 and older, up to 55. Sex: any. Healthy volunteers: accepted.

You may not qualify if…

• Participants will be excluded if they:
• are not suitable to undergo an fMRI experiment due to certain implanted devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins, surgical clips or other implanted metal parts), body morphology, or claustrophobia. Justification: MR scanning is one of the primary measurement tools used in the protocol. Assessment tool(s): Prospective participants will fill out an MRI screening questionnaire and undergo an interview with an MR technologist. Questions concerning suitability for scanning will be referred to the MR Medical Safety Officer. Prospective participants will be questioned about symptoms of claustrophobia and placed in the mock scanner during their first visit to assess for possible difficulty tolerating the confinement of the scanner and for ability to fit into the scanner.
• have coagulopathies, history of, current superficial, or deep vein thrombosis, musculoskeletal abnormalities restricting an individual s ability to lie flat for extended periods of time. Justification: MR scanning sessions require participants to lie flat on their backs and remain perfectly still for approximately two hours. Therefore, conditions that would make that difficult (e.g. chronic back pain, significant scoliosis) or dangerous (e.g. familial hypercoagulability syndrome, history of thrombosis) will be exclusionary. Assessment tool(s): History and physical examination by an IRP clinician, supplemented with a trial of lying in the mock scanner to assess comfort issues.
• have HIV or Syphilis. Justification: HIV and Syphilis both can have central nervous system (CNS) sequelae, thus introducing unnecessary variability into the data. Assessment tool(s): Oral HIV followed by blood test if oral test is + and RPR+ (>1:8 without history of adequate treatment).
• regularly use some prescriptions (e.g., antidepressants, benzodiazepines, antipsychotics, anticonvulsants, barbiturates), over-the-counter (e.g., cold medicine) or herbal medications (e.g., Kava, Gingko biloba, St. John s wort) that may alter CNS function, cardiovascular function, or neuronal-vascular coupling. Justification: The use of these substances may alter the fMRI signal and/or neural functions of interest in the current study. Assessment tool(s): History and comprehensive urine drug screening to detect antidepressants, benzodiazepines, antipsychotics, anticonvulsants, and barbiturates. The MAI/PI will use their medical/scientific judgment on a case-by-case basis.
• currently use moderate or strong CYP3A4 or 2D6 inhibitors not already covered by other exclusion criteria. Justification: Inhibitors of CYP3A4 or 2D6 may cause mild to moderately increased haloperidol concentrations when taken concomitantly, thereby increasing the possibility and/or duration of side effects associated with haloperidol administration. Assessment tool: All medications reported by participants will be reviewed for their effects on CYP3A4 and 2D6. Additionally, we will instruct participants to not consume grapefruit juice (2D6 inhibitor) on study days.
• have any current, or a history of, neurological illnesses including, but not limited to, seizure disorders, frequent migraines or on prophylaxis medications, multiple sclerosis, movement disorders, history of significant head trauma, or CNS tumor. Justification: Neurological diseases alter CNS function and, possibly, the neuronal-vascular coupling that forms the basis of the fMRI signal. Assessment tool(s): History and physical examination by a qualified IRP clinician, urine drug screening for anticonvulsants not disclosed by history. History of head trauma with loss of consciousness of more than 30 minutes or with post-concussive sequelae lasting more than two days, regardless of loss of consciousness, will be exclusionary.
• have any current, or a history of, major psychiatric disorders, including major depressive disorder (single past episode with at least three years symptom-free off medication will be allowed), schizophrenia, bipolar disorder or attention-deficit/hyperactivity disorder (ADHD), or are currently under antidepressant or antipsychotic medication treatment. Justification: Psychiatric disorders may be accompanied by alternations in brain structure and/or function. Assessment tool(s): Computerized SCID, Beck Depression Inventory, Beck Anxiety Inventory, Adult ADHD Self-Report Scales and clinical interview confirmation by clinician.
• are cognitively impaired or learning disabled. Justification: Cognitive impairment and learning disabilities may be associated with altered brain functioning in regions recruited during laboratory task performance. Cognitive impairment may affect one s ability to give informed consent. Assessment tool(s): History examination and Wechsler Abbreviated Scale of Intelligence (WASI). IQ estimate must be greater than or equal to 85.
• have significant cardiovascular or cerebrovascular conditions. Justification: Such conditions may alter blood flow, the fMRI signal and other autonomic signals, and increase risks associated with nicotine patch use. Assessment tool(s): History and physical exam, including EKG.
• have QTc greater than 450. Justification: Haloperidol may increases the risk of Torsades de Pointes and QTc prolongation. Assessment tool: EKG.
• have any other major medical condition that in the view of the investigators would compromise the safety of an individual during participation. Justification: Many illness not explicitly covered here may increase risk or alter important outcome measures. Assessment tool(s): History and physical examination by an IRP clinician and CBC, urinalysis, NIDA chemistry panel (liver function tests, electrolytes, kidney function). The following lab values will result in exclusion from the study:
• Hemoglobin < 10 g/dl
• White Blood Cell Count < 2400/microL
• Liver Function Tests > 3 times normal
• Serum glucose > 200 mg/dl
• Urine protein > 2+
• Estimated glomerular filtration rate <60ml/min
• pregnant, planning to become pregnant, or breastfeeding. Justification: Study procedures and drugs used in the current protocol may complicate pregnancy or be transferred to nursing children. Assessment tool/s: Urine pregnancy tests will be conducted at the beginning of each scanning visit.
• The MAI will retain discretion to exclude based on less extreme lab results. After the screening process has been completed, the MAI will take into account all data collected in order to decide if there is an existing medical illness that would compromise participation in this research.

Where it is running

• National Institute on Drug Abuse — Baltimore, Maryland, United States

Full record on ClinicalTrials.gov

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