Evaluation of [123I] AV94 and SPECT in Subjects With Alzheimer Disease in Comparison to Healthy Subjects

Alzheimer Disease Clinical Trial

— AV94  

Official title:

Evaluation of [123I] AV94 and SPECT as a Marker of Beta-amyloid Protein Deposition in Subjects With Alzheimer Disease in Comparison to Healthy Subjects

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00605059
• Other study ID #: AV94
• Status: Terminated
• Phase: Phase 1
• First received: January 16, 2008
• Last updated: October 5, 2010
• Start date: August 2007
• Est. completion date: June 2008

Study information

• Verified date: October 2010
• Source: Institute for Neurodegenerative Disorders
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The main objectives of this proposal are as follows:

To assess the dynamic uptake and washout of 123-I AV94, a potential imaging biomarker for β-amyloid burden in brain, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and Alzheimer's (AD) subjects

To perform blood metabolite characterization of 123-I AV94 in healthy and AD subjects to determine the metabolic fate and nature of metabolites in assessment of 123-I AV94 as a single photon computed tomography (SPECT) brain imaging agent

Evaluate the test/retest reproducibility of 123-I AV94 and SPECT in AD subjects and healthy controls

Description:

General Design and Methods. The underlying goal of this study is to assess 123-I AV94 SPECT imaging as a tool to detect ß-amyloid deposition in the brain of AD research participants and age- and gender-matched healthy subjects. All study procedures will be conducted at the Institute for Neurodegenerative Disorders (IND) and Molecular NeuroImaging (MNI) in New Haven, CT. Approximately 20 patients with Alzheimers disease (AD) and 10 healthy controls will be recruited to participate in this study. Healthy controls will be examined to ensure that there is no evidence of neurodegenerative changes including cognitive decline. Informed consent will be obtained for all. All subjects will undergo a screening evaluation including baseline clinical laboratory testing, a baseline physical and neurological evaluation and baseline cognitive evaluations. Subjects will be asked to undergo a bolus injection of 123-I AV94. Subjects will undergo serial SPECT imaging scans and serial venous plasma sampling for measurement of 123-I AV94 in plasma (both protein bound and free) over a period of up to 6 hours. Subjects may be asked to undergo a second imaging visit between 2 and 6 weeks following the initial imaging visit following similar procedures to the initial imaging visit to evaluate the reproducibility of the imaging measure using this procedure. The imaging analyses will be performed by an image-processing specialist who will remain masked to the procedures employed with each imaging acquisition. The primary imaging outcome measure will be the brain regional distribution volumes expressed as a brain tissue to plasma ratio of the radioligand, 123-I AV94. Time to the peak uptake and amplitude of the peak uptake will be evaluated for all brain regions and the results for the AD patients and controls will be compared. For those subjects undergoing repeat imaging visits, the data from the initial scan will be compared to the second scan to determine which offers the reproducibility of the imaging outcome measure.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 2008
• Est. primary completion date: June 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 50 Years and older

Eligibility

INCLUSION CRITERIA: ALZHEIMER DISEASE

• The participant is 50 years or older.

• Written informed consent is obtained.

• Participants have a clinical diagnosis of Alzheimer's disease based on National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) criteria.

• Mini-Mental Status Exam score < 25.

• Modified Hachinski Ischemia Scale score of = 4.

• Geriatric Depression Scales (GDS) = 10.

• For females, non-child bearing potential or negative urine or blood pregnancy test on day of 123-I AV94 injection.

EXCLUSION CRITERIA: ALZHEIMER DISEASE

• The subject has signs or symptoms of another neurodegenerative disease including Parkinson's disease, diffuse Lewy body dementia, or history of significant cerebrovascular disease.

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness

• The subject has any disorder that may interfere with drug absorption distribution, metabolism, or excretion (including gastrointestinal surgery).

• The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.

• Pregnancy

Concomitant therapy Patients may remain on a stable dose of anticholinesterase medication during the study. Use of donepezil (Aricept®), rivastigmine (Exelon®), galantamine (Razadyne®), tacrine (Cognex®), and memantine (Namenda®) are permitted during the study. Doses of these compounds must be stable for 2 months prior to the study. At each visit after the screening visit, the investigator will ask the patient whether any medications including OTC medications, were taken since the previous visit.

Use of antipsychotics for agitation and benzodiazepines for insomnia or anxiety is permitted. However, the use of these agents is not permitted within the 8 hours prior to administration of cognitive testing.

INCLUSION CRITERIA: HEALTHY VOLUNTEERS

• The participant is 50 years or older.

• Written informed consent is obtained.

• Negative history of neurological or psychiatric illness based on evaluation by a research physician.

• Mini-Mental Status Exam score =28.

• For females, non-child bearing potential or negative urine or blood pregnancy test on day of 123-I AV94 injection.

EXCLUSION CRITERIA: HEALTHY VOLUNTEERS

• The subject has a clinically significant abnormal laboratory value and/or clinically significant unstable medical or psychiatric illness.

• The subject has any disorder that may interfere with drug absorption distribution, metabolism, or excretion (including gastrointestinal surgery).

• The subject has evidence of clinically significant gastrointestinal, cardiovascular, hepatic, renal, hematological, neoplastic, endocrine, neurological, immunodeficiency, pulmonary, or other disorder or disease.

• Pregnancy

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Alzheimer Disease

Intervention

Drug:
• [123I]AV94
Evaluation of [123I] AV94 and SPECT as a Marker of Beta-amyloid Protein Deposition in Subjects With Alzheimer Disease in Comparison to Healthy Subjects

Locations

Country	Name	City	State
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Molecular NeuroImaging, LLC	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Institute for Neurodegenerative Disorders

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess the dynamic uptake and washout of 123-I AV94, a potential imaging biomarker for ß-amyloid burden in brain, using single photon emission computed tomography (SPECT) in similarly aged healthy controls and Alzheimer's (AD) subjects		1 year	No
Secondary	To perform blood metabolite characterization of 123-I AV94 in healthy and AD subjects to determine the metabolic fate and nature of metabolites in assessment of 123-I AV94 as a single photon computed tomography (SPECT) brain imaging agent		1 year	No
Secondary	Evaluate the test/retest reproducibility of 123-I AV94 and SPECT in AD subjects and healthy controls		1 year	No