Evaluation of 5-[123I]-A-85380 and SPECT Imaging in Individuals With Parkinsons Disease - Full Text View

Sponsors and Collaborators:	Institute for Neurodegenerative Disorders Department of Defense
Information provided by:	Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier:	NCT00397696

Purpose

The underlying goal of this study is to assess [123I] 5-IA and SPECT imaging as a tool to detect nicotinic receptor activity in the brain of PD patients. All study procedures will be conducted at the Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging (MNI) in New Haven, CT. Approximately 10 patients with a diagnosis of PD without cognitive changes will be recruited to participate in this study. Patients will be eligible to participate if they have a diagnosis of PD of more than 2 years duration and have no significant cognitive changes.

Condition	Intervention	Phase
Parkinson Disease	Procedure: [123I] 5-IA and SPECT imaging	Phase II

Genetics Home Reference related topics: familial paroxysmal nonkinesigenic dyskinesia Parkinson disease

MedlinePlus related topics: Degenerative Nerve Diseases Parkinson's Disease

Drug Information available for: BaseLine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Diagnostic, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	Evaluation of 5-[123I]-A-85380 and SPECT Imaging as a Marker of Nicotinic Receptor Density in the Brain of Parkinson Disease Subjects

Further study details as provided by Institute for Neurodegenerative Disorders:

Primary Outcome Measures:

VT', the equilibrium distribution volume in brain regions determined from an MRI-directed region-of-interest (ROI) analysis [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Baseline imaging VT' compared to the follow-up imaging study to the reliability of the nicotinic [123I] 5-IA imaging. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	10
Study Start Date:	November 2006
Estimated Primary Completion Date:	November 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Procedure: [123I] 5-IA and SPECT imaging All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, a baseline physical and neurological evaluation and baseline cognitive evaluations using the MMSE, the ANAM computerized cognitive battery, and other tests of executive function. All subjects will be evaluated with United Parkinson Disease Rating Scales (UPDRS) following an overnight withdrawal of anti-parkinson medication. Subjects will be asked to undergo an injection of [123I] 5-IA followed by SPECT imaging as described below. A second [123I] 5-IA and SPECT imaging study will be obtained for reliability testing between 2 weeks and 2 months following the initial [123I] 5IA imaging session.

Arms

Assigned Interventions

1: Experimental

Procedure: [123I] 5-IA and SPECT imaging

All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, a baseline physical and neurological evaluation and baseline cognitive evaluations using the MMSE, the ANAM computerized cognitive battery, and other tests of executive function. All subjects will be evaluated with United Parkinson Disease Rating Scales (UPDRS) following an overnight withdrawal of anti-parkinson medication. Subjects will be asked to undergo an injection of [123I] 5-IA followed by SPECT imaging as described below. A second [123I] 5-IA and SPECT imaging study will be obtained for reliability testing between 2 weeks and 2 months following the initial [123I] 5IA imaging session.

Detailed Description:

All subjects will undergo written informed consent and a screening evaluation including baseline clinical laboratory testing, a baseline physical and neurological evaluation and baseline cognitive evaluations using the MMSE, the ANAM computerized cognitive battery, and other tests of executive function. All subjects will be evaluated with United Parkinson Disease Rating Scales (UPDRS) following an overnight withdrawal of anti-parkinson medication. Subjects will be asked to undergo an injection of [123I] 5-IA followed by SPECT imaging as described below. A second [123I] 5-IA and SPECT imaging study will be obtained for reliability testing between 2 weeks and 2 months following the initial [123I] 5IA imaging session.

The primary imaging outcome measure will be VT', the equilibrium distribution volume in brain regions is determined from an MRI-directed region-of-interest (ROI) analysis. The baseline imaging VT' will be compared to the follow-up imaging study to the reliability of the nicotinic [123I] 5-IA imaging.

Eligibility

Ages Eligible for Study:	21 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

The presence of idiopathic Parkinson disease
A clear clinical response to dopaminergic therapy treatment
Hoehn and Yahr Stages < 3;
2-7 year Duration from time of diagnosis.
Mini-mental status exam score of >24,
For females, non-child bearing potential or negative urine pregnancy test on day of [123I] 5-IA injection.

Exclusion Criteria:

Secondary Parkinsonism;
Nicotine dependence or use within the previous 12 months prior to enrollment;
Treatment with Aricept (donepezil), Exelon (rivastigmine), Cognex (tacrine) within the past 30 days; treatment with medications that bind to the nicotinic receptor.
Clinically significant clinical laboratory value and/or medical or psychiatric illness;
Mini-mental status exam score of ≤24.
The subject has evidence of clinically significant thyroid disease, gastrointestinal, cardiovascular, hepatic, renal, hematologic, neoplastic, endocrine, neurologic, immunodeficiency, pulmonary, or other medical or psychiatric disorder;
The subject has received an investigational drug within 30 days of the screening visit;
Pregnancy

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00397696

Contacts

Contact: Liz Paul, coordinator	203-401-4300	epaul@indd.org
Contact: Barbara Fussell, RN	203-401-4300	bfussell@indd.org

Locations

United States, Connecticut
Institute for Neurodegenerative Disorders	Recruiting
New Haven, Connecticut, United States, 06510
Contact: Danna Jennings, MD 203-401-4300
Contact: Barbara Fussell, RN 203-401-4300
Principal Investigator: Kenneth Marek, MD
Institute for Neurodegenerative Disorders	Recruiting
New Haven, Connecticut, United States, 06510
Contact: Elizabeth Paul 203-401-4300 Epaul@indd.org
Principal Investigator: John Seibyl, MD
Sub-Investigator: Danna Jennings, MD
Sub-Investigator: Kenneth Marek, MD

Sponsors and Collaborators

Institute for Neurodegenerative Disorders

Department of Defense

Investigators

Principal Investigator:

John Seibyl, MD

Institute for Neurodegenerative Disorders

More Information

Publications:

Pirozzolo FJ, Hansch EC, Mortimer JA, Webster DD, Kuskowski MA. Dementia in Parkinson disease: a neuropsychological analysis. Brain Cogn. 1982 Jan;1(1):71-83.

Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967 May;17(5):427-42. No abstract available.

Seibyl JP, Marek KL, Quinlan D, Sheff K, Zoghbi S, Zea-Ponce Y, Baldwin RM, Fussell B, Smith EO, Charney DS, et al. Decreased single-photon emission computed tomographic [123I]beta-CIT striatal uptake correlates with symptom severity in Parkinson's disease. Ann Neurol. 1995 Oct;38(4):589-98.

Seibyl JP. Imaging studies in movement disorders. Semin Nucl Med. 2003 Apr;33(2):105-13. Review.

Marek K, Jennings D, Seibyl J. Single-photon emission tomography and dopamine transporter imaging in Parkinson's disease. Adv Neurol. 2003;91:183-91. Review. No abstract available.

Marek K, Jennings D, Seibyl J. Dopamine agonists and Parkinson's disease progression: what can we learn from neuroimaging studies. Ann Neurol. 2003;53 Suppl 3:S160-6; discussion S166-9. Review. No abstract available.

Louis M, Clarke PB. Effect of ventral tegmental 6-hydroxydopamine lesions on the locomotor stimulant action of nicotine in rats. Neuropharmacology. 1998 Dec;37(12):1503-13.

Parain K, Hapdey C, Rousselet E, Marchand V, Dumery B, Hirsch EC. Cigarette smoke and nicotine protect dopaminergic neurons against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine Parkinsonian toxin. Brain Res. 2003 Sep 12;984(1-2):224-32.

O'Neill MJ, Murray TK, Lakics V, Visanji NP, Duty S. The role of neuronal nicotinic acetylcholine receptors in acute and chronic neurodegeneration. Curr Drug Targets CNS Neurol Disord. 2002 Aug;1(4):399-411. Review.

Gale C, Martyn C. Tobacco, coffee, and Parkinson's disease. BMJ. 2003 Mar 15;326(7389):561-2. No abstract available. Erratum in: BMJ. 2003 Mar 22;326(7390):614. Gale, Chris [corrected to Gale, Catharine].

Quik M, Kulak JM. Nicotine and nicotinic receptors; relevance to Parkinson's disease. Neurotoxicology. 2002 Oct;23(4-5):581-94. Review.

Mitsuoka T, Kaseda Y, Yamashita H, Kohriyama T, Kawakami H, Nakamura S, Yamamura Y. Effects of nicotine chewing gum on UPDRS score and P300 in early-onset parkinsonism. Hiroshima J Med Sci. 2002 Mar;51(1):33-9.

Ross GW, Petrovitch H. Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. Drugs Aging. 2001;18(11):797-806. Review.

Kelton, M.C., et al., The effects of nicotine on Parkinson's disease. Brain Cogn, 2000. 43(1-3): p. 274-82.

Aubert I, Araujo DM, Cecyre D, Robitaille Y, Gauthier S, Quirion R. Comparative alterations of nicotinic and muscarinic binding sites in Alzheimer's and Parkinson's diseases. J Neurochem. 1992 Feb;58(2):529-41.

Zoghbi SS, Tamagnan G, Baldwin MF, Al-Tikriti MS, Amici L, Seibyl JP, Innis RB. Measurement of plasma metabolites of (S)-5-[123I]iodo-3-(2-azetidinylmethoxy)pyridine (5-IA-85380), a nicotinic acetylcholine receptor imaging agent, in nonhuman primates. Nucl Med Biol. 2001 Jan;28(1):91-6.

Responsible Party:	Institute for Neurodegenerative Disorders ( Danna Jennings, MD )
Study ID Numbers:	5-IA02
Study First Received:	November 7, 2006
Last Updated:	July 23, 2008
ClinicalTrials.gov Identifier:	NCT00397696
Health Authority:	United States: Food and Drug Administration

Keywords provided by Institute for Neurodegenerative Disorders:

Parkinson
imaging
nicotinic receptors

Study placed in the following topic categories:

Ganglion Cysts
Movement Disorders
Parkinson Disease
Basal Ganglia Diseases

Central Nervous System Diseases
Parkinsonian Disorders
Neurodegenerative Diseases
Brain Diseases

Additional relevant MeSH terms:

Nervous System Diseases

ClinicalTrials.gov processed this record on January 14, 2009