Preclinical Imaging Biomarkers of Alzheimer's Disease Neuropathology in Young Adults With Youth-onset Diabetes: a Proof-of-concept Study

The goal of the study is to characterize preclinical Alzheimer's Disease and related dementias (AD/ADRD) neuropathology in a selected group of young adults with youth-onset diabetes, and an age-similar group of young adults without diabetes.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Diabetes, Youth Onset
• Intervention / Treatment: Drug: PI-2620 tracer

Detailed Description

The goal of the current proof-of-concept study is to characterize brain structural, functional, and molecular imaging biomarkers of preclinical Alzheimer's Disease and related dementias (AD/ADRD) neuropathology in a selected group of young adults with youth-onset diabetes (Y-DM; type 1 diabetes [T1D], n=5; type 2 diabetes [T2D], n=5) from the SEARCH for Diabetes in Youth study cohort, and an age-similar group of young adults without diabetes (n=5). This study will quantify structural and functional imaging biomarkers of AD/ADRD neuropathology via magnetic resonance imaging by assessing gray matter (GM) volume/cortical thickness, as well as GM and white matter (WM) microstructure, resting state functional network connectivity (rsfMRI), and cerebral blood flow (CBF) and WM hyperintensity volume. This study will additionally quantify brain tau density via positron emission tomography as the gold-standard measure of preclinical AD/ADRD neuropathology.

• Study Type: Observational
• Enrollment (Actual): 14

Contacts and Locations

• Study Contact: Name: Jennifer Truong, MPH; Phone Number: 3037247703; Email: jennifer.truong@cuanschutz.edu
• Study Contact Backup: Name: Allison Shapiro, PhD, MPH; Phone Number: 3037241148; Email: allison.shapiro@cuanschutz.edu

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Lifecourse Epidemiology of Adiposity and Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

The study population will consist of young adults with youth-onset type 1 diabetes and type 2 diabetes from the SEARCH for Diabetes in Youth study cohort, and an age-similar group of young adults (18-40 years old) without diabetes.

Description

Inclusion Criteria:

• Part of the SEARCH for Diabetes in Youth study cohort or
• Age 18-40
• Without diabetes

Exclusion Criteria:

• Head trauma with loss of consciousness >30 minutes
• Claustrophobia
• Metal in the body
• Major psychiatric disorder (eg. schizophrenia, bipolar, and major depression)
• Neurological conditions affecting cognition (eg. epilepsy)
• Stroke
• If female, breastfeeding, plan to become pregnant or are pregnant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
T1D; Young adults with youth-onset type 1 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort	Drug: PI-2620 tracer; Following published manufacturer guidelines for Flutemetamol (VizamylTM), Flortaucipir (TauvidTM) and PI-2620 tracer administration162, all participants will be given a 370 MBq (10 mCi) single intravenous bolus (total volume 10mL) of the radiotracer, followed with an intravenous flush of 0.9% sodium chloride injection. Radiotracer administration and participant monitoring will be conducted by trained personnel from the CU-RIC.
T2D; Young adults with youth-onset type 2 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort	Drug: PI-2620 tracer; Following published manufacturer guidelines for Flutemetamol (VizamylTM), Flortaucipir (TauvidTM) and PI-2620 tracer administration162, all participants will be given a 370 MBq (10 mCi) single intravenous bolus (total volume 10mL) of the radiotracer, followed with an intravenous flush of 0.9% sodium chloride injection. Radiotracer administration and participant monitoring will be conducted by trained personnel from the CU-RIC.
NDM; Age-similar group of young adults without diabetes (n=5)	Drug: PI-2620 tracer; Following published manufacturer guidelines for Flutemetamol (VizamylTM), Flortaucipir (TauvidTM) and PI-2620 tracer administration162, all participants will be given a 370 MBq (10 mCi) single intravenous bolus (total volume 10mL) of the radiotracer, followed with an intravenous flush of 0.9% sodium chloride injection. Radiotracer administration and participant monitoring will be conducted by trained personnel from the CU-RIC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Temporal lobe volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR	Baseline
Temporal lobe cortical thickness in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR	Baseline
Whole brain white matter hyperintensities volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Structural cerebrovascular disease via Sagittal 3D FLAIR	Baseline
Regional homogeneity of the default mode network in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Resting-state functional connectivity via Axial T2* EPI fcMRI	Baseline
Whole brain cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Cerebral blood flow or perfusion via Axial 3D pCASL	Baseline
Whole brain fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Gray matter and white matter microstructure via Diffusion Kurtosis Imaging	Baseline
Standardized uptake value ratio for hippocampal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Tau accumulation via positron emission tomography with PI-2620 radiotracer	Baseline
Standardized uptake value ratio for entorhinal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Tau accumulation via positron emission tomography with PI-2620 radiotracer	Baseline
Standardized uptake value ratio for cerebral to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Tau accumulation via positron emission tomography with PI-2620 radiotracer	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Whole brain gray matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR	Baseline
Whole brain white matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR	Baseline
Perivascular space in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Structural cerebrovascular disease via Sagittal 3D FLAIR	Baseline
Atlas based region of interest cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Cerebral blood flow via Axial 3D pCASL	Baseline
Atlas based region of interest fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes	Gray matter and white matter microstructure via Diffusion Kurtosis Imaging	Baseline

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: American College of Radiology
• Investigators: Principal Investigator: Allison Shapiro, PhD, MPH, University of Colorado - Anschutz Medical Campus; Principal Investigator: Christopher T Whitlow, MD, PhD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2022
• Primary Completion (Actual): May 31, 2023
• Study Completion (Actual): May 31, 2023

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 21, 2022
• First Posted (Actual): April 28, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2023
• Last Update Submitted That Met QC Criteria: November 28, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Diabetes, Youth Onset; Positron Emission Tomography Imaging
• Additional Relevant MeSH Terms: Mental Disorders; Glucose Metabolism Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immune System Diseases; Autoimmune Diseases; Neurocognitive Disorders; Endocrine System Diseases; Neurodegenerative Diseases; Dementia; Tauopathies; Diabetes Mellitus; Diabetes Mellitus, Type 2; Diabetes Mellitus, Type 1; Alzheimer Disease
• Other Study ID Numbers: 22-0608

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