Evaluation of [123I] AV51 and SPECT as a Marker of Beta-Amyloid Protein Deposition in Subjects With Alzheimer Disease in Comparison to Healthy Subjects

This study has been completed.
Sponsor:
Information provided by:
Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier:
NCT00556660
First received: November 8, 2007
Last updated: July 23, 2008
Last verified: July 2008
  Purpose

The main objectives of this proposal are as follows:

To assess the dynamic uptake and washout of 123-I AV51, 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 AV51 in healthy and AD subjects to determine the metabolic fate and nature of metabolites in assessment of 123-I AV51 as a single photon computed tomography (SPECT) brain imaging agent

Evaluate the test/retest reproducibility of 123-I AV51 and SPECT in AD subjects and healthy controls


Condition Intervention Phase
Alzheimer Disease
Procedure: SPECT scan
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Screening

Resource links provided by NLM:


Further study details as provided by Institute for Neurodegenerative Disorders:

Primary Outcome Measures:
  • To assess the dynamic uptake and washout of 123-I AV151, 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 [ Time Frame: 6 mos ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: September 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
SPECT imaging
Procedure: SPECT scan
To assess the dynamic uptake and washout of 123-I AV151, 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

Detailed Description:

Research Plan:

General Design and Methods. The underlying goal of this study is to assess 123-I AV51 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 AV51. Subjects will undergo serial SPECT imaging scans and serial venous plasma sampling for measurement of 123-I AV51 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 AV51. 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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

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:

  • 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 AV51 injection.

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:

  • 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 AV51 injection.

Exclusion Criteria:

Healthy control subjects will be excluded from participation for the following reasons:

  • 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

Alzheimer's subjects will be excluded from participation for the following reasons:

  • 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00556660

Locations
United States, Connecticut
Institute for Neurodegenerative Disorders
New Haven, Connecticut, United States, 06510
Molecular NeuroImaging, LLC
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Institute for Neurodegenerative Disorders
Investigators
Principal Investigator: Danna L Jennings, MD Institute for Neurodegenerative Disorders
  More Information

No publications provided

Responsible Party: Danna Jennings, MD, Institute for Neurodegenerative Disorders
ClinicalTrials.gov Identifier: NCT00556660     History of Changes
Other Study ID Numbers: AV51 001
Study First Received: November 8, 2007
Last Updated: July 23, 2008
Health Authority: United States: Institutional Review Board
United States: Food and Drug Administration

Keywords provided by Institute for Neurodegenerative Disorders:
Alzheimer
SPECT

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 22, 2014