Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease
- Conditions
- Mild Cognitive ImpairmentAlzheimer Disease
- Interventions
- Registration Number
- NCT03560960
- Lead Sponsor
- Boston University
- Brief Summary
In this multi-center study, the investigators plan to develop a simple blood-based test for early detection of Alzheimer's disease (AD). The test is based on a single injection of Pramlintide, an amylin analogue and FDA-approved drug currently used for treatment of diabetes. The investigative team has provided evidence in humans with full-blown AD and AD-relevant mouse models that a single injection of Pramlintide transiently renders the blood brain barrier (BBB) more permeable to Amyloidbeta (Aß) peptides, allowing their efflux from the brain compartment into the blood. This Aß efflux causes a corresponding transient elevation of blood levels of Aß, the magnitude of which the applicants believe is proportional to the brain amyloid load as determined by AV-45 PET. The measured difference in the level of plasma Aß taken just before and a short time after injection should reveal the magnitude of the transient increase in blood Aß levels. Supportive preliminary data comes from later stage (full-blown) AD patients with more in-depth background studies in Tg2576 and 5X Familial Alzheimer's Disease (FAD) mouse models. If successful for use as an early AD (i.e., at the Mild Cognitive Impairment \[MCI\] stage) biomarker, this could be a game-changer for both early AD diagnostics and clinical trials aimed at identifying and testing the efficacy of drugs useful for treatment of AD at early stages. If Pramlintide is effective in releasing mobile pools of Aß from the brain into the blood, this could also have some therapeutic potential, with the goal of reducing brain amyloid load.
Three groups of particpants will be studied: 1) amnestic MCI with or without positive AD imaging pathology, 2) probable AD with positive imaging AD pathology, and 3) controls who have normal cognition and do not have memory complaints.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 57
- Current research subjects at the BU ADC, VA BHS, or IU ADC
- A consensus diagnosis of probable AD, amnestic MCI, or control
- BMI of 20-35
- Probable AD subjects must be confirmed for positive AD pathology in the CNS
- Probable AD subjects must have a designated research proxy signed before they became demented.
- Diabetes mellitus
- Gastroparesis
- Use of insulin, pramlintide, other injectable anti-hyperglycemic agents, such as glucagon like peptide-1 (GLP-1), or oral anti-diabetic products
- Unexplained hypoglycemia (glucose ≤ 60 mg/dL) or hyperglycemia (glucose ≥ 126 mg/dL) pre-injection
- History of stroke
- Seizures or use of anti-seizure medications
- History of brain injury and loss of consciousness
- Diagnosed cerebral amyloid angiopathy (CAA)
- Infection within 1 month
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Probable AD Pramlintide challenge test Participants with probable AD with positive imaging AD pathology will receive the pramlintide challenge test. Control- Normal Cognition Pramlintide challenge test Participants with normal cognition without any memory complaints will receive the pramlintide challenge test. Amnestic MCI Pramlintide challenge test Participants with amnestic MCI with or without positive AD imaging pathology will receive the pramlintide challenge test.
- Primary Outcome Measures
Name Time Method Plasma metabolic changes in blood 5, 30, 60, and 180 min after a pramlintide challenge test Changes in 2. Metabolism biomarkers associated with amylin: leptin, GLP-1, RBP4, Insulin R, ApoE, and ApoJwill be measured applying high-density multiplex ELISA assays (RayBiotech, Norcross, GA)
Plasma Aβ and t-tau changes 5, 30, 60, and 180 min after challenge test Plasma Aβ1-40 and Aβ1-42 data will be analyzed. For each peptide, the mean ± SD, median, 25%, 75%, and range
Plasma inflammatory changes 5, 30, 60, and 180 min after challenge test Changes in proinflammatory-related biomarkers: particularly the IL-1β/IL-1Ra pathway, as well as GM-CSF, G-CSF, Trem2, CD36, and CD163, CD68 will be measured applying high-density multiplex ELISA assays (RayBiotech, Norcross, GA)
- Secondary Outcome Measures
Name Time Method Change in Trailmaking Test Part B baseline, 12 and 24 months post challenge Trailmaking Test Part B range is from 0-300 seconds, we expect an increase in this test
Change in Controlled Oral Word Association Test baseline, 12 and 24 months post challenge Controlled Oral Word Association Test has no range, we expect this to be decreased
Change in MMSE baseline, 12 and 24 months post challenge MMSE range is from 1-30, we expect a positive challenge test will have a decrease of MMSE
Change in WMS-III Logical Memory baseline, 12 and 24 months post challenge WMS-III range is from 0-25, we expect a decrease in WMS-III Logical memory
Change in CDR baseline, 12 and 24 months post challenge CDR range is from 0-3, we expect a positive challenge test for increased CDR score
Change in NAB baseline, 12 and 24 months post challenge We expect NAB to be decreased
Change in CLOX paradigm baseline, 12 and 24 months post challenge CLOX paradigm range is from 0-3, we expect a decrease in this paradigm
Trial Locations
- Locations (3)
Indiana University Alzheimer Disease Center
🇺🇸Indianapolis, Indiana, United States
BU Alzheimer Disease Center
🇺🇸Boston, Massachusetts, United States
Memory Center VA Boston Healthcare
🇺🇸Jamaica Plain, Massachusetts, United States