Imaging Biomarkers in Obesity

Obesity Clinical Trial

Official title:

Neuroinflammation and Alzheimer's Disease Imaging Biomarkers in Midlife Obesity

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05077579
• Other study ID #: 202102186
• Status: Recruiting
• Start date: October 18, 2021
• Est. completion date: December 31, 2026

Study information

• Verified date: February 2023
• Source: Washington University School of Medicine
• Contact: Cyrus Raji, MD, PhD
• Phone: 314-273-0334
• Email: craji[@]wustl.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

High body fat at midlife, as evidenced by overweight or obese body mass index (BMI), is increasingly understood as a risk factor for Alzheimer's disease. However, the underlying processes and mechanisms that may underlie this risk remains unknown. With this project, the Investigator proposes to create a new cohort of cognitively normal 120 midlife individuals, age 40-60 years. The investigator and research staff will characterize the participant's overweight or obese status using metabolic tests including, an oral glucose tolerance test, fasting plasma insulin, fasting plasma glucose, and hemoglobin A1c measurements. This testing will generate categories of metabolically abnormal overweight and obese (MAOO), metabolically normal overweight and obese (MNOO), and metabolically normal lean participants (MNLP). Research staff will evaluate differences between these groups on neuroimaging with the newer classification framework of Alzheimer's biomarkers with amyloid (A), tau (T), and neurodegeneration (N), or ATN. Neurodegeneration will be assessed by atrophy on brain MRI as reflected by regional volumes on Freesurfer. Staff will also evaluate MR neuroimaging markers for neuroinflammation using a newer method called diffusion basis spectrum imaging (DBSI), developed at the Mallinckrodt Institute of Radiology at Washington University in St. Louis in collaboration with The Charles F. and Joanne Knight Alzheimer's Disease Research Center (Knight ADRC).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 31, 2026
• Est. primary completion date: May 1, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 40 Years to 60 Years

Eligibility

Inclusion Criteria:

1. Male and female, 40-60 years of age and any race;

2. MMSE = or greater than 25 or a Clinical Dementia Rating Scale (CDR)=0;

3. Willing and able to undergo MRI

4. Willing to complete PET scans, including [11C]PiB and 18F-AV-1451 (Flortaucipir) radioactive tracer injection under protocols IRB #201409014 & 201906028

5. Willing to participate in the metabolic subtyping of metabolically normal or abnormal overweight or obese status for the following three groups: a. Group 1: MAOO criteria: i. BMI =25 but <45 kg/m2; ii. Maximum body circumference < 165 cm to ensure participants fit into the PET/CT and MR scanners; iii. Fasting blood glucose: =100 mg/dl or blood glucose 2 h after an OGTT: =140 or fasting insulin: >20 µu/ml; b. Group 2: MNOO criteria: i. BMI = 25 but <45 kg/m2; ii. Maximum body circumference < 165 cm to ensure participants fit into the PET/CT and MR scanners; iii. Blood glucose 2 h after an OGTT: iv. HbA1c < 5.7% v. Fasting insulin: < 20 µu/ml; c. Group 3: MNLP criteria: i. BMI =18.5 but < 25.0 kg/m2; ii. Maximum body circumference < 165 cm to ensure subjects fit into the PET/CT and MR scanners; iii. Fasting blood glucose: < 100 mg/dl; iv. Blood glucose 2 h after an OGTT: < 140 mg/dl; v. HbA1c < 5.7% vi. Fasting insulin: < 20 µu/ml;

Exclusion Criteria:

1. Any condition that in the opinion of the Investigator or designee could increase the risk to the participant, limit the participant's ability to tolerate the research procedures or interfere with the collection of the data, (e.g., currently taking a drug for treatment of obesity);

2. Intend to have bariatric surgery;

3. Inability to tolerate to lie still during the scanning procedures (e.g., severe, chronic back pain);

4. Severe claustrophobia;

5. Women who are currently pregnant or breast-feeding;

6. Currently receiving an active obesity study drug (or placebo) or in an obesity clinical trial;

7. Laboratory Evaluations exclusion: • Oral glucose tolerance test should not be performed in patients who already fulfill the criteria for diabetes mellitus. These include: - History of Type 1 or 2 diabetes mellitus - Prior documentation of a fasting plasma glucose >7.0 mmol/L or two or more occasions or clinical symptoms of diabetes e.g. polydipsia, polyuria, ketonuria and rapid weight loss with a random plasma glucose of >11.1 mmol/L • Other contraindications for venous access as part of OGTT or blood draws: - Venous fibrosis or shunt grafts in both upper extremities - Ongoing cellulitis or infection, particularly in the upper extremities. - Presence of a hematoma at the site of vascular access. - History of hypoglycemic encephalopathy that can occur with prolonged fasting

8. MRI exclusion: • Contraindications to MRI (e.g., certain incompatible electronic medical devices that make it potentially unsafe for the individual to participate). All participants must be willing to undergo at least two MRI screenings, supervised by Level II MRI personnel as designated by the American College of Radiology (ACR).

Related Conditions & MeSH terms

• Alzheimer Disease
• Metabolic Disease
• Metabolic Diseases
• Obesity

Locations

Country	Name	City	State
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Cyrus A Raji

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Sub-aims-sex differences in atrophy and neuroinflammation	Will examine sex differences in atrophy and neuroinflammation. We will also investigate sex differences in amyloid and tau deposition across the overweight/obese and lean groups. These will be measured through the results of the blood tests, MRI scan & data from the PET scans.	10 hours
Primary	Aim - increased atrophy in MAOO compared to MNOO and MNLP participants	we hypothesize increased atrophy in MAOO compared to MNOO and MNLP particularly in regions important for AD pathology such as the hippocampus and hippocampal sub-regions. These will be measured through the results of the blood tests, MRI scan & data from the PET scans.	10 hours
Secondary	Aim 2- higher burden of white matter neuroinflammation on DBSI	We hypothesize a higher burden of white matter neuroinflammation on DBSI in MAOO in relation to other overweight and obese groups. The MRI scan will be used to measure these outcomes.	10 hours
Secondary	Aim 3-increased amyloid and tau deposition on brain	We hypothesize increased amyloid and tau deposition on brain PET in MAOO versus other groups. The PET scan data will be used to measure these outcomes.	10 hours