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

Completed

• Conditions: Diabetes Mellitus, Type 2; Diabetes, Youth Onset; Diabetes Mellitus, Type 1
• Interventions: Drug: PI-2620 tracer

• Registration Number: NCT05350514
• Lead Sponsor: University of Colorado, Denver

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-04-12
• Study First Submitted QC: 2022-04-21
• Study First Posted: 2022-04-28
• Study Start: 2022-07-19
• Primary Completion: 2023-05-31
• Study Completion: 2023-05-31
• Status Verified: 2023-11
• Last Update Submitted: 2023-11-28
• Last Update Posted: 2023-11-30

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
T1D	PI-2620 tracer	Young adults with youth-onset type 1 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort
NDM	PI-2620 tracer	Age-similar group of young adults without diabetes (n=5)
T2D	PI-2620 tracer	Young adults with youth-onset type 2 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Lifecourse Epidemiology of Adiposity and Diabetes Center; 🇺🇸 Aurora, Colorado, United States