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

NCT05350514 | Completed FDA Drug

• 1 other identifier: 22-0608
• Study Type: observational
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Youth Onset

Keywords

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes, Youth Onset; Magnetic Resonance Imaging; Positron Emission Tomography Imaging

Outcome Measures

Primary Outcomes (9)

• 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 Outcomes (5)

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

  Baseline

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

  Baseline

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

  Baseline

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

  Baseline

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

  Baseline

Study Arms (3)

T1D

Young adults with youth-onset type 1 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort

Drug: PI-2620 tracer

T2D

Young adults with youth-onset type 2 diabetes (n=5) from the SEARCH for Diabetes in Youth study cohort

Drug: PI-2620 tracer

NDM

Age-similar group of young adults without diabetes (n=5)

Drug: PI-2620 tracer

Interventions

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.

NDM; T1D; T2D

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• 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.

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• American College of Radiology: collaborator

Study Sites (1)

Lifecourse Epidemiology of Adiposity and Diabetes Center

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Allison Shapiro, PhD, MPH

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

• Christopher T Whitlow, MD, PhD

  Wake Forest University Health Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 1 Day
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 12, 2022
• First Posted: April 28, 2022
• Study Start: July 19, 2022
• Primary Completion: May 31, 2023
• Study Completion: May 31, 2023
• Last Updated: November 30, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)