Clinical trial NCT03560960: Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease
Official title: Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Alzheimer Disease
Mild Cognitive Impairment
Keywords: Early AD diagnosis
Pramlintide challenge test
Amyloid
Amyloid PET imaging
CSF Aβ
CSF pTau
Cognitive evaluation
Lead sponsor: Boston University
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-06-19
Enrollment: 57
Sex: ALL
Minimum age (years): 60
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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 biomarker (i.e., at the Mild Cognitive Impairment (MCI) stage), 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 participants 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.


Eligibility criteria: Inclusion Criteria:

* Current research subjects at the BU , Memory Center VA Boston Healthcare, or Indiana University Alzheimer Disease Center
* A consensus diagnosis of probable Alzheimer's Disease (AD), amnestic mild cognitive impairment (MCI), or control
* BMI of 20-35
* Probable AD subjects must be confirmed for positive AD pathology in the central nervous center (CNS0
* Probable AD subjects must have a designated research proxy signed before they became demented.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Plasma Aβ 1-40 levels
timeFrame: baseline, 5, 30, 60, and 180 min after challenge test
measure: Plasma Aβ1-42 levels
timeFrame: baseline, 5, 30, 60, and 180 min after challenge test
measure: Plasma Aβ and t-tau changes
timeFrame: baseline, 5, 30, 60, and 180 min after challenge test
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University Alzheimer Disease Center
state: Indiana
city: Boston
country: United States
facility: BU Alzheimer Disease Center
state: Massachusetts
city: Jamaica Plain
country: United States
facility: Memory Center VA Boston Healthcare
state: Massachusetts
Study officials:
affiliation: Boston Medical Center and BUSM
name: Wendy Qiu, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: