Phase II Study for Amyloid Binding Imaging Study of [18F]AV-45 in Patients With Mild Cognitive Impairment, Alzheimer's Disease and Healthy Volunteers

Phase 2

• Conditions: Alzheimer's Disease
• Interventions: Drug: [18F]AV-45 PET amyloid binding imaging

• Registration Number: NCT01238458
• Lead Sponsor: Chang Gung Memorial Hospital

Brief Summary

This study will recruit a total of 150 evaluable subjects (30 cognitively normal volunteers, and 60 MCI(Mild cognitive impairment), and 60 AD(Alzheimer's disease), respectively) Each evaluable subject involved in this study must fulfill all the inclusion and exclusion criteria according the subject grouping.

Safety measurement will be evaluated by medical history, vital signs, physical examinations, laboratory examinations and collecting of adverse events.

This study is expected to be completed in a period of 3 years.

Detailed Description

The primary objective of this protocol is to address the feasibility of clinical utilization of \[18F\]AV-45 in various neurodegenerative diseases. Specifically, we will expand the database of \[18F\]AV-45 PET imaging in Alzheimer's disease and MCI patients to refine the definition of a positive scan in patient with AD and MCI as compared to healthy control. Secondary, we will expand the safety database of \[18F\]AV-45 PET imaging. In addition, the image characteristics and prevalence of Aß positivity will be evaluated in different subsets of MCI and AD patients.

Study Timeline

• Study Start: 2009-11
• Study First Submitted: 2010-10-21
• Study First Submitted QC: 2010-11-09
• Study First Posted: 2010-11-10
• Primary Completion: 2011-11
• Status Verified: 2012-09
• Last Update Submitted: 2012-09-27
• Last Update Posted: 2012-09-28
• Study Completion: 2013-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Both genders ≥ 50 years old.
• Written and dated informed consent by self or by legal representative, to be obtained before any of the study procedures.
• 30 cognitively normal volunteers with no evidence of significant cognitive impairment by history and psychometrictesting (MMSE > 24).
• 60 subjects with a diagnosis of AD according to the NINCDS-ADRDA criteria.
• 60 subjects with a diagnosis of MCI

Exclusion Criteria

1. Pregnant or becoming pregnant during the study (as documented by pregnancy testing at screening or at any date during the study according to the PI discretion) or current breast feeding.

2. Modified Hachinski ischemic score of >4 or those who meet the NINDS-AIREN criteria for vascular dementia.

3. Any subject who has a clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness.

   • Clinically significant hepatic, renal, pulmonary, metabolic, or endocrine disturbances, especially thyroid disease;

   • Current clinically significant cardiovascular disease. Clinically significant cardiovascular disease usually includes one or more of the following:

     • cardiac surgery or myocardial infarction within the last 6 months;
     • unstable angina
     • coronary artery disease that required a change in medication within the last 3 months
     • decompensated congestive heart failure
     • significant cardiac arrhythmia or conduction disturbance, particularly those resulting in atrial or ventricular fibrillation, or causing syncope, near syncope, or other alterations in mental status
     • severe mitral or aortic valvular disease
     • uncontrolled high blood pressure
     • congenital heart disease
     • clinically significant abnormal result on ECG, including but not limited to QTc>450 msec iii. Clinically significant infectious disease, including AIDS or HIV infection or active hepatitis B, active hepatitis C, HIV-1, or HIV-2

4. History of drug or alcohol abuse within the last year, or prior prolonged history of abuse.

5. Patients who have the evidence of neurodegenerative disorders other than AD, cognitive impairment resulting from trauma or brain damage, brain infarction, clinically significant psychiatric disease, epilepsy, are excluded.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
[18F]AV-45 PET amyloid binding imaging	[18F]AV-45 PET amyloid binding imaging	-

Primary Outcome Measures

Name	Time	Method
To expand the safety database of [18F]AV-45 PET imaging	one year	To expand the database of \[18F\]AV-45 PET imaging in Alzheimer's disease and MCI patients to refine the definition of a positive scan in patient with AD and MCI as compared to healthy control.

Secondary Outcome Measures

Name	Time	Method
To expand the safety database of [18F]AV-45 PET imaging	two year	To expand the safety database of \[18F\]AV-45 PET imaging Safety variables include adverse event count, lab parameters, vital signs, and ECG. Comparison will be generally made to baseline, as appropriate.; To understand prevalence of Aß positivity in patients with MCI and AD. Images will be visually examined by a trained radiologist or nuclear medicine physician who is blinded to the subject diagnosis and will be reported as either Aβ positive (AD-like) or Aβ negative (not AD-like). The prevalence of Aß positivity in patients with MCI and AD will be recorded for comparison.