Dopaminergic Neuromodulation of Decision Making in Young and Middle-Aged Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Dopamine D2 receptor availability (binding potential)
研究概览
简要总结
Financial decisions are made during pre-retirement age that can influence financial well-being for the rest of an individual's life. This proposal aims to construct a more comprehensive model of the specific psychological and neural mechanisms that support financial decisions in young adulthood and late middle age. In Part 1 of this study (covered in Institutional Review Board (IRB) # 141812), middle-age and young adults complete basic cognitive, motivational, and decision making tasks and are studied with functional magnetic resonance imaging (fMRI) to determine the relation between neural circuit activation and individual and age-related differences in decision making. In part II of the study, aspects of dopamine functioning are studied using positron emission tomography (PET) scanning to determine whether individual differences in dopamine functions are related to the decision-making and fMRI measures collected in Part 1 of the study. Dopamine measures include baseline D2 receptor availability, amphetamine induced dopamine release and dopamine transporter (DAT) levels, which provides a more comprehensive evaluation of dopamine functions than in prior studies linking individual differences in dopamine to behavioral, cognitive or decision-making traits.
详细描述
The study involves 4 sessions: 1) Informed Consent; 2) Oral d-amphetamine with Fallypride PET; 3) Placebo with Fallypride PET; and 4) PE2I PET. The oral amphetamine/placebo conditions utilize a double-blind counterbalanced design. The 3 PET sessions will be conducted within a 6 week window, and whenever possible within a 2 week time period.
- Informed consent session: Informed consent will be obtained by Dr. Zald or approved study personnel after inclusion and exclusion criteria have been reviewed. Participants are screen for inclusion/exclusion as part of a separate IRB protocol (Vanderbilt IRB protocol #141812). After the consent processes is completed, participants will also complete the Tests of Vigilance and Attention (TOVA: http://www.tovatest.com/), which assesses attention abilities and motor impulsivity.
2 & 3) D-amphetamine/Placebo Fallypride PET Sessions
Participants complete two [18F]fallypride PET sessions, each lasting approximately 7 hours. Scan sessions will all start in the afternoon. Subjects will be instructed to have a moderate lunch with no more than a single cup of coffee or tea before coming to the PET center. If the scan is not expected to start until after 5 PM, a light snack may also be eaten. After determination of blood pressure, respirations, pulse, temperature, an intravenous line will be placed in the forearm, the subject will complete ratings of their mood (using the and PANAS and the Amphetamine Interview Schedule administered on a laptop computer), and participants will have a brief neurological exam conducted by one of the study MDs. An initial blood sample for genotyping or estradiol levels (women only) will be acquired.
The subject will then receive a 0.43 mg/kg oral dose of d-amphetamine or placebo. The investigational pharmacy will prepare capsules with 10 mg, and 2.5 mg with dosing rounded to the nearest 2.5 mgs (for instance an individual weighing 80 kg would be rounded up to a 35 mg dose). The drug dose and placebo, will be placed by the pharmacist in identical containers, labeled with the subject's ID and scan day number. A sealed envelope indicating whether the dose is d-amphetamine or placebo will be included in case there is a need to break the blinding. The study physician, can quickly access this information if there is appearance of an adverse drug effect. Otherwise the study physician and experimenters who have contact with the participant will remain blind until the participant has completed their second PET scan. If a participant has an adverse event that necessitates any medication, or other intervention, the blind will be broken to the participant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Double (Participant, Investigator)
盲法说明
The participant and the research analyst running their session are both blind, however a PET tech is unmasked who monitors the participant for any adverse reactions.
入排标准
- 年龄范围
- 20 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Medically, psychiatrically and neurologically healthy individuals between the 20-30 or 50-65 years of age. Subjects must be able to give informed consent, have an estimated intelligence quotient of greater than 80, and be a fluent English speaker.
排除标准
- •Any condition which would interfere with or be a risk for MRI ( e.g. extreme obesity, claustrophobia, cochlear implant, metal fragments in eyes, cardiac pacemaker, neural stimulator, metallic body inclusions or other metal implanted in the body, facial tattoos with iron pigment). Difficulty lying on one's back and claustrophobia are also exclusions.
- •History of major psychiatric illness (including recurrent major depressive episodes or a depressive episode in the past 10 years, any anxiety disorders in the last 10 years, any history of bipolar disorder or psychotic disorder, a history of substance dependence (or substance abuse lasting more than 2 years), or any eating disorder in which symptoms persisted for more than two years
- •Current tobacco use, alcohol intake greater than 8 ounces of whiskey or equivalent per week, use of any psychotropic medication for the past 6 months (other than occasional use of benzodiazepines for sleep), psychostimulants taken more than 5 times in the subject's life, current marijuana use 4 Neurological illness (other than headache or strictly peripheral nerve disturbance), or head trauma (including more than 2 concussions)
- •Significant untreated or unregulated major medical condition deemed likely to influence cognitive functioning, dopaminergic functioning or neuroimaging measures. Diabetes is an exclusion even if well-controlled.
- •History of Syncope during blood draws 7) Anemia or hematocrit <
- •Participation in any research studies in the past year that involved radiation, or exposure to radiation on a routine basis due to their occupation.
- •High blood pressure (Systolic B.P. > 150 in participants under the age of 61, or > 145 in subjects > 61 years of age). Diagnosis of labile hypertension. Abnormal EKG indicating potential cardiac risk under conditions of increased blood pressure.
- •Current pregnancy or lactation or plans to become pregnant during the study timeframe.
- •As part of the screening process in protocol # 141812, participants are initially screened with a brief telephone interview to determine if they meet medical, psychiatric and neurological criteria (all information screened is included in attached screening form). Participants are not consented until after completion of the brief health interview (a waiver of consent is in place in order to perform the initial telephone screening). After being consented participants complete a medical history and physical exam with one of the study MD's. They also complete a psychiatric interview (SCID-IV or V) with one of the trained psychology research assistants or Dr. Zald, and finally an EKG is completed. Participants are not enrolled in the present phase of the study until all exclusion criteria are assessed and they are withdrawn from the study if new information arises that would alter the conclusion regarding any of the inclusion/exclusion criteria after enrollment.
研究组 & 干预措施
Amphetamine
One oral dose of dextroamphetamine (0.43 mg/kg) up to a maximum dose of 45mg. The dose is administered in 10mg and 2.5mg capsules prepared by the Vanderbilt Investigational Drug Services (IDS). Note: We are not testing the effect of dextro-amphetamine on a symptom. Rather it is part of the diagnostic intervention that is used to measure dopamine release assessed as the decline in [18F]fallypride binding relative to baseline.
干预措施: Dextroamphetamine (Drug)
Amphetamine
One oral dose of dextroamphetamine (0.43 mg/kg) up to a maximum dose of 45mg. The dose is administered in 10mg and 2.5mg capsules prepared by the Vanderbilt Investigational Drug Services (IDS). Note: We are not testing the effect of dextro-amphetamine on a symptom. Rather it is part of the diagnostic intervention that is used to measure dopamine release assessed as the decline in [18F]fallypride binding relative to baseline.
干预措施: [18F]Fallypride (Diagnostic Test)
Placebo
One oral placebo dose, with capsules prepared by the Vanderbilt Investigational Drug Services (IDS). This provides the baseline against which dopamine release is measured.
干预措施: Placebo (Drug)
Placebo
One oral placebo dose, with capsules prepared by the Vanderbilt Investigational Drug Services (IDS). This provides the baseline against which dopamine release is measured.
干预措施: [18F]Fallypride (Diagnostic Test)
[18F]-FE-PE2I
[18F]-FE-PE2I is a radioligand for measuring dopamine transporters with positron emission tomography (PET). All participants complete this arm. The arm does not include administration of amphetamine or placebo.
干预措施: [18F]-FE-PE2I (Diagnostic Test)
结局指标
主要结局
Dopamine D2 receptor availability (binding potential)
时间窗: 3- 6.5 hours
D2 receptor availability is measured using positron emission tomography (PET) and the D2/D3 receptor radioligand \[18F\] fallypride. Contrast between receptor availability after amphetamine versus placebo forms the primary measure of dopamine release induced by amphetamine.
次要结局
- Decision Making Task 2(1-3 hours)
- Cognitive Task 3(1 - 2 hours)
- Motor Task 1(1 - 2 hours)
- Change in Spontaneous Eye Blink Rate(1-2 hours)
- Cognitive Task 2 (verbal fluency)(1 - 2 hours)
- Quantification of Dopamine Transporter Levels(0 - 2 hours)
- Decision Making Task 1(1-3 hours)
- Cognitive Task 1 (processing speed)(1 - 2 hours)
研究者
David Zald
Cornelius Vanderbilt Professor of Psychology and Professor of Psychiatry
Vanderbilt University