An Open Label Phase I/II Study of the Safety and Dopamine Transporter Binding Properties of C-11 Altropane in Normal Human Subjects and in Subjects With ADHD

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the Binding Potential in subjects with ADHD and adults without ADHD: the intent being to demonstrate that C-11 Altropane PET can be used to differentiate adults with ADHD from healthy control subjects.

Detailed Description
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This protocol seeks to replicate and extend our investigation of DAT binding in adults with ADHD with specific aims: To examine dopamine transporter (DAT) receptor binding potential in adults with ADHD, using PET scanning with 11C altropane as the ligand. We hypothesize that compared to adults without ADHD, adults with ADHD will have greater DAT binding that will not be accounted by psychiatric comorbidity or age. To examine the relationship of DAT binding to clinical features of ADHD. We hypothesize that DAT binding will be positively correlated with a) severity of ADHD symptoms and b) neuropsychological and interpersonal dysfunction. To examine the relationship between DAT binding and genetic risk factors. We hypothesize that DAT binding will be specifically associated with homozygosity of the DAT (480) gene in adults with ADHD and not with other ADHD-associated genetic markers (e.g., DRD4-7, D2, DBH).

Official Title
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An Open Label Phase I/II Study of the Safety and Dopamine Transporter Binding Properties of C-11 Altropane in Normal Human Subjects and in Subjects With ADHD

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Radiation: PET imaging using C-11 altropane as the ligand.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent to participate in the study. Age: 18 - 55 If female, non-pregnant, non-nursing with a negative serum pregnancy test and using an adequate form of birth control. Supine and standing blood pressure within the range 110/60 to 150/90 mmHg. Heart rate, after resting for 5 minutes, within the range 46-90 beats/min. Subjects who are within 20% of the ideal weight for height Right handed Diagnosis of DSM-IV ADHD (current), as manifested in clinical evaluation and confirmed by structured interview (for ADHD study subjects). Subjects without a diagnosis of DSM-IV ADHD (lifetime), as manifested in clinical evaluation and confirmed by structured interview (for control study subjects). Exclusion Criteria: Diagnosis of any psychotic disorder, bipolar disorder, severe depression, severe anxiety, or Autism. Subjects with mild mood, oppositional, conduct, and anxiety disorders may be permitted to participate if considered appropriate by the investigator Scores of Baseline Scales: Hamilton Depression Scale > 17 (out of a possible 67 on the 21-item scale)(Hamilton 1960) Beck Depression Inventory > 19 (out of a possible 63 on the 21-item scale)(Beck, Ward et al. 1961) Hamilton Anxiety Scale > 21 (out of a possible 56 on the 14-item scale)(Hamilton 1959) History of head trauma with loss of consciousness, organic brain disorders, seizures, or neurosurgical intervention. Any clinically significant chronic medical condition, in the judgement of the investigator. Mental impairment as evidenced by an I.Q. <75. Subject must be off any investigational drug for at least 4 weeks prior to the start of the study. Exposure to dopamine receptor antagonists, including stimulant medications (e.g. methylphenidate) or buproprion within the previous three (3) months to the start of the study. Exposure to non-stimulant ADHD medications (e.g. atomoxetine) within the previous 4 weeks to the start of the study. Exposure to radiopharmaceuticals within four (4) weeks prior to PET scan. Subjects receiving psychotropic medication. Any clinically significant abnormality in the screening laboratory tests, vital signs, or 12-lead ECG, outside of normal limits. Any woman of childbearing potential who is seeking to become pregnant or suspects that she may be pregnant. Subjects with a known recent history (within the past six (6) months) of illicit drug or alcohol dependence.

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| un-medicated subjects with ADHD<br> | Radiation: PET imaging using C-11 altropane as the ligand.<br>* A one-injection protocol will be used for the study. C-11 Altropane will be injected manually as an intravenous bolus.<br>|
| subjects without ADHD<br> | Radiation: PET imaging using C-11 altropane as the ligand.<br>* A one-injection protocol will be used for the study. C-11 Altropane will be injected manually as an intravenous bolus.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The DAT receptor occupancy of OROS MPH and Metadate CD in adults with and without ADHD using PET scanning with C-11 Altropane. | PET imaging will be acquired using either a HR+ or Siemens Biograph 64 PET/CT camera. | Subjects will lie still in the PET camera for a 90 minute period. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neuropsychological tests | Cognitive-neuropsychological functioning will be examined by selected tests that are thought to reflect basic deficits in ADHD, mainly those believed to measure components of attention and prefrontal brain systems. | Examination of cognitive-neuropsychological functioning will take approximately 2.5 hours to complete. | 
| Genotyping | Genotyping will be performed using a custom markers for dopamine-related genes (DAT, DRD4-7, D2, and DBH). | A sample of blood (2 tablespoons) will be drawn from all subjects. |