DaTSCAN Imaging in Aging and Neurodegenerative Disease

Study Overview
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Brief Summary
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The investigators propose using DaTscan in patients with REM sleep behavior disorder (RBD), mild cognitive impairment (MCI), Parkinson's disease (PD), dementia with Lewy bodies (DLB), Alzheimer's disease (AD), and other neurodegenerative syndromes and disorders, to test several hypotheses - some confirmatory, and some novel. Such use will provide new data on the potential clinical and research utility of DaTscan in neurodegenerative diseases. The findings on DaTscan will be correlated with clinical diagnoses and other multimodal imaging studies (e.g., MRI, MRS, FDG-PET, and amyloid-PET) to enhance our understanding of neurodegenerative diseases.

Detailed Description
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Lewy body disease (LBD) is one of the most common neurodegenerative diseases and second only to Alzheimer's disease in terms of prevalence, disability, and societal/financial burden. The phenotypic variability of LBD is striking, as it can manifest as the well-known disorder of Parkinson's disease without (PD) and with dementia (PDD), as well as DLB, MCI, REM sleep behavior disorder (RBD), pure autonomic failure (PAF), and other syndromes. One biomarker which is both highly sensitive and specific for evolving LBD in the setting of dementia is DaTscan [Ioflupane (123I)] imaging, in which loss of functional dopaminergic neuron terminals in the striatum as assessed by DaTscan reflects underlying LBD in those with dementia and particularly dementia with Lewy bodies (DLB). DaTscan is the one of the first radiopharmaceutical agents available to detect DaT distribution within the brain. DaTscan imaging involves injection of the Ioflupane radioligand followed by imaging using a standard single photon emission computed tomography (SPECT) scanner. DaTscan provides visualization of the dopamine transporter (DaT) distribution within the striata (i.e., striatal uptake, or striatal signal) by SPECT imaging in patients presenting with symptoms or signs suggestive of dopaminergic neurodegeneration. Most DaTscan studies published to date have been conducted in centers outside of the US. DaTscan has not been studied in the syndrome of MCI, and minimally in corticobasal degeneration (CBD). Very little normative data exists in the aged population either. The FDA-approved indication is to assist in the evaluation of adult patients with suspected Parkinsonian syndromes (PS). In these patients, DaTscan may be used to help differentiate essential tremor from tremor due to Parkinsonian syndromes (such as idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy). DaTscan will be used as an adjunct to other diagnostic evaluations. Identifying dopaminergic dysfunction is also important in other settings such as those with cognitive impairment with or without parkinsonism, and in subjects with REM sleep behavior disorder. The findings on DaTscan in subjects with these various disorders will be correlated with clinical diagnoses and other multimodal imaging studies (e.g., MRI, MRS, FDG-PET, and amyloid-PET) to enhance our understanding of neurodegenerative diseases. A subset of subjects will undergo a 2nd DaTscan at least 1 year after the initial scan was performed to determine if changes over time provide any prognostic information.

Official Title
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DaTSCAN Imaging in Aging and Neurodegenerative Disease

Conditions
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Dementia, Parkinsonism, Mild Cognitive Impairment, REM Sleep Behavior Disorder

Intervention / Treatment
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* Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)
* Device: Single photon emission computed tomography (SPECT) scan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of one of the syndromes of interest using established criteria Age 40-90 inclusive MMSE score above 10 No active medical disorder that could preclude participation Stable medication regimen over previous four weeks Absence of certain medications that could significantly impact the DaTscan findings For those with dementia, caregiver that is with the patient at least 4 hours/day for at least 5 days per week For those with dementia, or severe parkinsonism, patient and caregiver willing and able to participate in all study-related procedures Patient is capable of giving informed consent, or if appropriate, has caregiver capable of giving consent on the subject's behalf. Exclusion Criteria: Does not fulfill criteria for any of the desired diagnoses Age <40 or >90 Women with intact uterus and not post-menopausal unless pregnancy test performed at screening is negative Women who are pregnant or are breast-feeding an infant MMSE score <10 Active medical disorder that could preclude participation in this protocol Hypersensitivity to the radioligand, cocaine, or iodine (including seafood allergy) Myocardial infarction or cerebral infarct over preceding year, stable or unstable angina, known symptomatic coronary artery disease Renal or liver disease viewed by the physician to be too severe to warrant DaTscan infusion/imaging History of significant alcohol or drug abuse Any other medical disorder considered by the study physicians as inappropriate for this protocol Patient or caregiver unwilling or unable to participate in all study-related procedures Caregiver is not with a patient with dementia or severe parkinsonism at least 4 hours/day for at least 5 days/week Patient or caregiver unwilling or unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Alzheimer's Disease<br>Alzheimer's Disease | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: Dementia with Lewy Bodies<br>Dementia with Lewy Bodies | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: Frontotemporal Dementia<br>Frontotemporal Dementia | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: Parkinson's Disease<br>Parkinson's Disease | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: Corticobasal Degeneration<br>Corticobasal Degeneration | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: Essential Tremor<br>Essential Tremor | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: Mild Cognitive Impairment<br>Mild Cognitive Impairment | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|
| Experimental: REM sleep behavior disorder<br>REM sleep behavior disorder | Drug: I-123 Ioflupane solution injection prior to SPECT scan (DaTscan)<br>* I-123 Ioflupane solution for injection into a living test subject. The iodine introduced during manufacture is a radioactive isotope, I-123, and it is the properties of this isotope that makes the solution visible to a gamma camera on SPECT imaging. I-123 has a half-life of approximately 13 hours and a gamma photon energy of 159 keV making it an good radionuclide for medical imaging. DaTscan is administered by intravenous cannula. The scan is carried out 3-6 hours post injection.<br>Device: Single photon emission computed tomography (SPECT) scan<br>* Single-photon emission computed tomography(SPECT)is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera. However, it is able to provide true 3D information. This information is typically presented as cross-sectional slices through the patient, but can be freely reformatted or manipulated as required.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlate the DaTscan findings with clinical diagnosis | The primary endpoint is to correlate the DaTscan findings with clinical diagnosis | Participants will be followed to 1-3 days after scan. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of DaTscan imaging | The primary safety/tolerability endpoint relates to side effects associated with DaTscan imaging | Participants will be followed for 1-3 days after scan. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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dementia, parkinsonism, mild cognitive impairment, REM sleep behavior disorder