A Study to Assess Regional Cerebral Blood Flow as an Alzheimer's Disease Biomarker Compared to Positron Emission Tomography in Patients With Mild-to-Moderate Alzheimer's Disease and Cognitively Normal Elderly Subjects (Study MK-0000-068)(COMPLETED)

A Two-Part Cross-Sectional and Longitudinal Study to Assess Regional Cerebral Blood Flow by Dynamic Arterial Spin Labeling as an Alzheimer's Disease Biomarker as Compared to FDG-PET in Patients With Mild-to-Moderate Alzheimer's Disease and Cognitively Normal Elderly Subjects

The aim of the study is to determine if regional cerebral blood flow, measured by dynamic arterial spin labeling (dASL), can be a biomarker for stage of Alzheimer's disease. The study is designed to be conducted in 2 parts in participants with mild to moderate Alzheimer's disease, and participants with normal cognition. Various imaging studies will be done using magnetic resonance imaging (MRI) and positron emission tomography (PET) along with neurocognitive assessments. Participants who meet the study-entry criteria will have up to 8 study visits. Repeat imaging studies may be required if the initial data are incomplete or un-interpretable. The maximum number of PET scans during the study will be limited to four.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Other: MRI; Other: FDG-PET

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

The prospective participant must meet, at least, all of the criteria below (among others determined by the study staff) to be eligible for study participation.

The participant:

• Has mild-to-moderate Alzheimer's Disease (AD), OR is considered cognitively normal;
• Has been on stable doses of any regularly used medications for 4 weeks prior to study start;
• Must have been on a stable dose for 12 weeks prior to study start, of any medications taken for AD.

Exclusion Criteria:

If the prospective participant meets any of the criteria below (among others determined by the study staff) they will NOT be eligible for study participation.

The participant:

• Is living in a nursing home or skilled nursing facility;
• Has severe AD;
• Cannot undergo MRI;
• Cannot undergo PET scans;
• Has a history of neurological or neurodegenerative disorders, other than AD within 2 years prior to study start;
• Has taken Tacrine or anti-parkinsonian medications within 3 months of study start;
• Has taken corticosteroids, blood thinners, narcotic analgesics, benzodiazepines, or certain antihistamines within 1 month of study start;
• Initiates, discontinues, or changes the dose of any AD treatment during the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AD Participants; Participants with a diagnosis of mild-to-moderate AD	Other: MRI; During the study all participants will have 4 total MRI scans: baseline, 1 week, 6 and 12 months.; Other: FDG-PET; 2 to 4 PET scans will be done over 12 months, 2 planned and 2 more if data from any of these are un-interpretable
Experimental: Cognitively Normal Elderly Participants; Elderly participants with no cognitive impairment	Other: MRI; During the study all participants will have 4 total MRI scans: baseline, 1 week, 6 and 12 months.; Other: FDG-PET; 2 to 4 PET scans will be done over 12 months, 2 planned and 2 more if data from any of these are un-interpretable

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Regional cerebral blood flow, as measured by dASL.	Part I: regional cerebral blood flow, measured by dASL at Baseline and 1 week in AD participants and cognitively normal controls. Part II: regional cerebral blood flow, measured at 6 months and 12 months in AD participants and normal control participants.	1 week, 6 and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of cerebral glucose consumption, MRglc, as measured by fludeoxyglucose-PET (FDG-PET)	Regional cerebral rate of glucose consumption, MRglc, as assessed by FDG-PET will be measured at Baseline in (Part I) and at 12 months in (Part II), in AD participants and normal control participants.	12 months
Resting state functional MRI blood-oxygen-level-dependent (fMRI BOLD) response	The resting state fMRI BOLD (blood-oxygen-level-dependent) signal will be evaluated for 'Goodness-of-Fit' to the default mode network at Baseline, 1 week, and 6 and 12 months in AD participants and normal control participants.	1 week, 6 and 12 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start: September 1, 2008
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: September 19, 2008
• First Submitted That Met QC Criteria: September 19, 2008
• First Posted (Estimate): September 23, 2008

Study Record Updates

• Last Update Posted (Estimate): August 11, 2015
• Last Update Submitted That Met QC Criteria: August 10, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Alzheimer's Disease, MRI, PET
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 0000-068; 2008_547

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No