Multi-Center Development of a Novel Diagnostic Test for Alzheimer's Disease (DTAD)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Drug: Pramlintide challenge test

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Alzheimer Disease Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • BU Alzheimer Disease Center
    • Jamaica Plain, Massachusetts, United States, 02130
      • Memory Center VA Boston Healthcare

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probable AD; Participants with probable AD with positive imaging AD pathology will receive the pramlintide challenge test.	Drug: Pramlintide challenge test; Enrolled subjects will have a pre-trial blood draw (3 ml) and will be placed with an IV needle for future blood draws. Pramlintide will be subcutaneously injected in the abdominal area. For each arm the participants will be randomized so that half will be given a dose of 0.8 mcg/kg and the other half of the arm a dose of 1.6 mcg/kg. Blood will be drawn before and at 5, 30, 60, and 180 min after injection. Vital signs and blood glucose will also be checked at these time points. Thirty minutes after the injection, subjects will be offered a standard meal. Subjects will have a final check of vital signs and blood glucose approximately 15 min before discharge.; Other Names: Symlin
Active Comparator: Amnestic MCI; Participants with amnestic MCI with or without positive AD imaging pathology will receive the pramlintide challenge test.	Drug: Pramlintide challenge test; Enrolled subjects will have a pre-trial blood draw (3 ml) and will be placed with an IV needle for future blood draws. Pramlintide will be subcutaneously injected in the abdominal area. For each arm the participants will be randomized so that half will be given a dose of 0.8 mcg/kg and the other half of the arm a dose of 1.6 mcg/kg. Blood will be drawn before and at 5, 30, 60, and 180 min after injection. Vital signs and blood glucose will also be checked at these time points. Thirty minutes after the injection, subjects will be offered a standard meal. Subjects will have a final check of vital signs and blood glucose approximately 15 min before discharge.; Other Names: Symlin
Active Comparator: Control- Normal Cognition; Participants with normal cognition without any memory complaints will receive the pramlintide challenge test.	Drug: Pramlintide challenge test; Enrolled subjects will have a pre-trial blood draw (3 ml) and will be placed with an IV needle for future blood draws. Pramlintide will be subcutaneously injected in the abdominal area. For each arm the participants will be randomized so that half will be given a dose of 0.8 mcg/kg and the other half of the arm a dose of 1.6 mcg/kg. Blood will be drawn before and at 5, 30, 60, and 180 min after injection. Vital signs and blood glucose will also be checked at these time points. Thirty minutes after the injection, subjects will be offered a standard meal. Subjects will have a final check of vital signs and blood glucose approximately 15 min before discharge.; Other Names: Symlin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Aβ 1-40 levels	Plasma Aβ1-40, also known as beta-amyloid 1-40, is a biomarker measured in the blood, and it is associated with the development of Alzheimer's disease. Specifically, higher plasma concentrations of Aβ1-40, particularly when combined with lower levels of Aβ1-42, are linked to an increased risk of dementia. The normal range for Aβ 1-40 levels in human plasma is generally considered to be less than 100 pg/mL, with most studies reporting values between 30 to 60 pg/mL.	baseline, 5, 30, 60, and 180 min after challenge test
Plasma Aβ1-42 levels	Plasma Aβ1-42, also known as beta-amyloid 1-42, is a protein fragment involved in the development of Alzheimer's disease. It is a form of amyloid-beta (Aβ) that is associated with the formation of plaques in the brain. Aβ1-42 is a key biomarker for Alzheimer's disease. Specifically, lower plasma concentrations of Aβ1-42, particularly when combined with higher levels of Aβ1-402, are linked to an increased risk of dementia. The reference interval for plasma Aβ1-42 levels in cognitively normal subjects is typically between 8.12 and 29.00 pg/mL.	baseline, 5, 30, 60, and 180 min after challenge test
Plasma Aβ and t-tau changes	Plasma total tau (t-tau) levels can indicate subclinical brain and cognitive deficits, potentially predicting the risk of neurodegenerative conditions in normal aging. Higher plasma t-tau levels have been associated with poorer cognitive function, reduced glucose uptake, thinning of the temporal lobe, and even increased risk of all-cause dementia. The reference range for plasma total tau (t-tau) is typically reported as 0.20-3.12 pg/mL	baseline, 5, 30, 60, and 180 min after challenge test

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in MMSE	MMSE range is from 1-30, we expect a positive challenge test will have a decrease of MMSE	baseline, 12 and 24 months post challenge
Change in CDR	CDR range is from 0-3, we expect a positive challenge test for increased CDR score	baseline, 12 and 24 months post challenge
Change in NAB	We expect NAB to be decreased	baseline, 12 and 24 months post challenge
Change in WMS-III Logical Memory	WMS-III range is from 0-25, we expect a decrease in WMS-III Logical memory	baseline, 12 and 24 months post challenge
Change in CLOX paradigm	CLOX paradigm range is from 0-3, we expect a decrease in this paradigm	baseline, 12 and 24 months post challenge
Change in Trailmaking Test Part B	Trailmaking Test Part B range is from 0-300 seconds, we expect an increase in this test	baseline, 12 and 24 months post challenge
Change in Controlled Oral Word Association Test	Controlled Oral Word Association Test has no range, we expect this to be decreased	baseline, 12 and 24 months post challenge

Collaborators and Investigators

• Sponsor: Boston University
• Collaborators: National Institute on Aging (NIA)
• Investigators: Principal Investigator: Wendy Qiu, MD PhD, Boston Medical Center and BUSM

Study record dates

Study Major Dates

• Study Start (Actual): February 4, 2020
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026

Study Registration Dates

• First Submitted: May 25, 2018
• First Submitted That Met QC Criteria: June 6, 2018
• First Posted (Actual): June 19, 2018

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Amyloid; Early AD diagnosis; Pramlintide challenge test; Amyloid PET imaging; CSF Aβ; CSF pTau; Cognitive evaluation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Physiological Effects of Drugs; Hypoglycemic Agents; pramlintide
• Other Study ID Numbers: H-37432; 1R01AG059424-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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