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| Sponsors and Collaborators: |
Institute for Neurodegenerative Disorders Molecular NeuroImaging |
|---|---|
| Information provided by: | Institute for Neurodegenerative Disorders |
| ClinicalTrials.gov Identifier: | NCT00612872 |
Purpose
To assess the dynamic uptake and washout of 123-I CLINDE, a potential imaging biomarker for inflammatory changes in brain, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and subjects with Alzheimer (AD) or Parkinson disease (PD).
To perform blood metabolite characterization of 123-I CLINDE in healthy and subjects with AD or PD to determine the nature of metabolites in assessment of 123-I CLINDE as a single photon computed tomography (SPECT) brain imaging agent.
Evaluate the test/retest reproducibility of 123-I CLINDE, and SPECT in AD and PD subjects and healthy controls
| Condition | Intervention | Phase |
|---|---|---|
|
Parkinson Disease Alzheimer Disease Healthy Controls Multiple Sclerosis |
Procedure: SPECT scan |
Phase I |
| Study Type: | Interventional |
| Study Design: | Diagnostic, Non-Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study |
| Official Title: | Evaluation of [123I]CLINDE and SPECT as a Marker of Inflammation in Subjects With Parkinson Disease or Alzheimer Disease and in Healthy Subjects |
| Estimated Enrollment: | 21 |
| Study Start Date: | January 2008 |
| Estimated Study Completion Date: | December 2009 |
| Estimated Primary Completion Date: | December 2009 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Experimental
Subjects will be injected with up to 5 mCi and not to exceed 5.5 (not >10% of 5 mCi limit) of 123-I CLINDE followed by serial SPECT imaging.
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Procedure: SPECT scan
Serial dynamic imaging will occur approximately at the following time frames, 6 x 10 minutes, then 6 x 20 minute over approximately 8 hours. The imaging will occur within 8 hours of the injection. Serial venous plasma samples (approximately ½ tablespoon for each sample) will be acquired appropriately every 30 minutes (based on the scanning interval schedule), commencing post injection and obtained up to 14 time points during each imaging visit.
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When microglia become activated they express peripheral benzodiazepine receptors (PBR) or binding sites on their mitochondrial membrane. PBRs are functionally and structurally distinct from central benzodiazepine receptors associated with y-aminiobutric acid (GABA)-regulated chloride channels.
PBRs are found in abundance in peripheral organs and hematologic cells, but are present at only very low levels in the normal central nervous system (Banati, 2002). CLINDE is a phenylimidazopyridine and appears to bind selectively to the PBR. In the absence of excessive blood in the CNS an increase CLINDE binding to PBR is a potential marker of microglial activation in the CNS. The increase in CLINDE binding may be an indicator of the transition of microglia from a resting to an activated state. When labeled with 123-I and used as a SPECT radiotracer, CLINDE may serve as an in vivo marker of microglial activation in Alzheimer disease and Parkinson disease. The 123-I radioactive tag offers distinct advantages for large-scale clinical imaging studies of anti-inflammatory targeted treatments as a marker of microglial activation and efficacy of therapeutic intervention. The half-life (13.1 h) of 123-I permits imaging in multiple subjects in a single research-dedicated imaging center, with multiple research subjects per day. This minimizes variability introduced in multi-center quantitative imaging trials where different cameras, image processing methods, and QA procedures all conspire to increase the variance imaging biomarkers. Using this model, our group pioneered a method to evaluate the loss of dopamine function in Parkinson's disease using a radioactive drug 123-I β-CIT which binds directly to dopamine nerve terminals. The adaptation of imaging agents like 123-I CLINDE as a biomarker of microglial activation in neurodegenerative diseases requires human validation studies. Expanding upon our previous work with b-amyloid ligands (123I-IMPY, 123-I MNI-187) for AD and dopamine transporter ligands (123-I B-CIT, Altropane) for PD, we desire to develop and characterize 123-I CLINDE as a potential marker for microglial activation in association with neuronal damage that may be applicable to multiple neurodegenerative diseases. Ultimately a marker of microglial activation could be used for large-scale quantitative brain imaging trials in AD or PD, specifically to investigate the agent as an objective biomarker in treatments aimed at reducing inflammatory changes in these conditions. The significance of this work lies in applying state-of-art quantitative neuroimaging tools to develop a relevant biomarker in individuals with neurodegenerative diseases with the intention of using this efficiently in large clinical imaging trials.
Eligibility| Ages Eligible for Study: | 30 Years to 50 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Alzheimer's Subject Selection. Subjects who have a clinical diagnosis of mild to moderate Alzheimer's disease will be recruited for this study. The following criteria will be met for inclusion of AD subjects in this study:
Parkinson's Subject Selection. Subjects who have a clinical diagnosis of mild to moderate Parkinson disease will be recruited for this study. The following criteria will be met for inclusion of PD subjects in this study:
Healthy Control Subject Selection. Healthy control subjects who have no neurological disease will be recruited for this study. The following criteria will be met for inclusion of healthy control subjects in this study:
Exclusion Criteria:
Alzheimer's subjects will be excluded from participation for the following reasons:
Parkinson's subjects will be excluded from participation for the following reasons:
Healthy control subjects will be excluded from participation for the following reasons:
Contacts and Locations| Contact: Barbara L. Fussell, RN | 203-401-4300 | bfussell@@indd.org |
| Contact: Wilma Uy | 203-401-4300 | wuy@indd.org |
| United States, Connecticut | |
| Institute for Neurodegenerative Disorders | Recruiting |
| New Haven, Connecticut, United States, 06510 | |
| Contact: Barbara Fussell, RN 203-401-4300 bfussell@indd.org | |
| Contact: Liz Paul 203-401-4300 epaul@indd.org | |
| Principal Investigator: Kenneth Marek, MD | |
| Sub-Investigator: Danna Jennings, MD | |
| Principal Investigator: | Danna L Jennings, M.D. | Institute for Neurodegenerative Disorders |
More Information
| Responsible Party: | Institute for Neurodegenerative Disorders ( Danna Jennings, MD ) |
| Study ID Numbers: | CLINDE 001, IND 100,863 |
| Study First Received: | January 16, 2008 |
| Last Updated: | January 30, 2009 |
| ClinicalTrials.gov Identifier: | NCT00612872 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
|
Ganglion Cysts Autoimmune Diseases Demyelinating Diseases Basal Ganglia Diseases Alzheimer Disease Central Nervous System Diseases Sclerosis Healthy Brain Diseases Neurodegenerative Diseases Cognition Disorders |
Inflammation Multiple Sclerosis Delirium, Dementia, Amnestic, Cognitive Disorders Movement Disorders Parkinson Disease Mental Disorders Demyelinating Autoimmune Diseases, CNS Parkinsonian Disorders Dementia Autoimmune Diseases of the Nervous System Delirium |
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Autoimmune Diseases Immune System Diseases Demyelinating Diseases Basal Ganglia Diseases Alzheimer Disease Nervous System Diseases Central Nervous System Diseases Sclerosis Brain Diseases Neurodegenerative Diseases Inflammation |
Pathologic Processes Multiple Sclerosis Delirium, Dementia, Amnestic, Cognitive Disorders Movement Disorders Parkinson Disease Mental Disorders Demyelinating Autoimmune Diseases, CNS Parkinsonian Disorders Dementia Tauopathies Autoimmune Diseases of the Nervous System |
