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Completed

NCT Number: NCT05350514

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.

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Key information

Age range

18 year–40 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Lifecourse Epidemiology of Adiposity and Diabetes Center

Aurora, Colorado, 80045, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

PI-2620 tracer

Drug

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.

Primary outcomes

  1. Temporal lobe volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR

  2. Temporal lobe cortical thickness in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR

  3. Whole brain white matter hyperintensities volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Structural cerebrovascular disease via Sagittal 3D FLAIR

  4. Regional homogeneity of the default mode network in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Resting-state functional connectivity via Axial T2* EPI fcMRI

  5. Whole brain cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Cerebral blood flow or perfusion via Axial 3D pCASL

  6. Whole brain fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Gray matter and white matter microstructure via Diffusion Kurtosis Imaging

  7. Standardized uptake value ratio for hippocampal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Tau accumulation via positron emission tomography with PI-2620 radiotracer

  8. Standardized uptake value ratio for entorhinal to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Tau accumulation via positron emission tomography with PI-2620 radiotracer

  9. Standardized uptake value ratio for cerebral to cerebellar comparison in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Tau accumulation via positron emission tomography with PI-2620 radiotracer

Secondary outcomes

  1. Whole brain gray matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR

  2. Whole brain white matter volume in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Voxel-based morphometry via Sagittal 3D Accelerated MPRAGE/IRSPGR

  3. Perivascular space in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Structural cerebrovascular disease via Sagittal 3D FLAIR

  4. Atlas based region of interest cerebral blood flow in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Cerebral blood flow via Axial 3D pCASL

  5. Atlas based region of interest fractional anisotropy in young adults with Type 1 diabetes, Type 2 diabetes, and young adults without diabetes

    Time frame: Baseline

    Gray matter and white matter microstructure via Diffusion Kurtosis Imaging

Sponsors and collaborators

Lead sponsor

University of Colorado, Denver

Other

Collaborators

  • American College of Radiology

Registry information

Important dates

Study start
2022
Primary completion
2023
Study completion
2023
First posted
Apr 28, 2022
Registry last updated
Nov 30, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

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This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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