Multi-Center Development of a Novel Diagnostic Test for Alzheimer’s Disease

Brief Title

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

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.
    


Study Phase

Early Phase 1

Study Type

Interventional


Primary Outcome

Plasma Aβ and t-tau changes

Secondary Outcome

 Change in MMSE

Condition

Alzheimer Disease

Intervention

Pramlintide challenge test

Study Arms / Comparison Groups

 Probable AD
Description:  Participants with probable AD with positive imaging AD pathology will receive the pramlintide challenge test.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

240

Start Date

February 4, 2020

Completion Date

July 2023

Primary Completion Date

July 2023

Eligibility Criteria

        Inclusion Criteria:

          -  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.

        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
      

Gender

All

Ages

60 Years - 90 Years

Accepts Healthy Volunteers

No

Contacts

Wendy Qiu, MD PhD, (617) 358-1886, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT03560960

Organization ID

H-37432

Secondary IDs

1R01AG059424-01

Responsible Party

Sponsor

Study Sponsor

Boston University

Collaborators

 National Institute on Aging (NIA)

Study Sponsor

Wendy Qiu, MD PhD, Principal Investigator, Boston Medical Center and BUSM


Verification Date

January 2022