This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Imaging Biomarkers in Obesity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05077579
Recruitment Status : Recruiting
First Posted : October 14, 2021
Last Update Posted : February 21, 2023
Sponsor:
Information provided by (Responsible Party):
Cyrus A Raji, Washington University School of Medicine

Study Description
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief 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).

Condition or disease
Alzheimer Disease Obesity Metabolic Disease

Study Design
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Observational
Estimated Enrollment : 240 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Neuroinflammation and Alzheimer's Disease Imaging Biomarkers in Midlife Obesity
Actual Study Start Date : October 18, 2021
Estimated Primary Completion Date : May 1, 2026
Estimated Study Completion Date : December 31, 2026

Resource links provided by the National Library of Medicine


Groups and Cohorts
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Group/Cohort
metabolically abnormal overweight & obese
metabolically normal overweight
obese and metabolically normal lean


Outcome Measures
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Aim - increased atrophy in MAOO compared to MNOO and MNLP participants [ Time Frame: 10 hours ]
    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.


Secondary Outcome Measures :
  1. Aim 2- higher burden of white matter neuroinflammation on DBSI [ Time Frame: 10 hours ]
    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.

  2. Aim 3-increased amyloid and tau deposition on brain [ Time Frame: 10 hours ]
    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.


Other Outcome Measures:
  1. Sub-aims-sex differences in atrophy and neuroinflammation [ Time Frame: 10 hours ]
    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.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   40 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
We currently have IRB-approved protocols covering ongoing imaging that meet the eligibility criteria. The Washington University Knight Alzheimer's Disease Research Center and the Center for Human Nutrition will refer participants . The Knight ADRC primarily recruits participants by means of word of mouth and public service announcements from the greater metropolitan St. Louis area. We will also coordinate these efforts with the Center for Human Nutrition to maximize potential participants from their studies. The Center for Human Nutrition has a long history (>30 years) of recruitment for research studies and has a large pool (>20,000) of pre-screened adults. A small percentage (~17%) of participants are referred by Washington University physicians. The Research Participant Registry/Volunteer for Health (VFH) Program at Washington University in St. Louis (https://vfh.wustl.edu) will also be utilized.
Criteria

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).
Contacts and Locations
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05077579


Contacts
Layout table for location contacts
Contact: Cyrus Raji, MD, PhD 314-273-0334 craji@wustl.edu
Contact: Nancy Hantler, BS, CCRC, ACRP-PM 314-362-7315 hantlern@wustl.edu

Locations
Layout table for location information
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: LaKisha A Lloyd, MS    314-362-7315    lloydl@wustl.edu   
Contact: Nancy A Hantler, BS    3143627315    hantlern@wustl.edu   
Sponsors and Collaborators
Cyrus A Raji
Investigators
Layout table for investigator information
Principal Investigator: Cyrus Raji, MD, PhD Washington University School of Medicine
More Information
Go to 
Top of Page Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Cyrus A Raji, Asst Prof of Radiology, Washington University School of Medicine
ClinicalTrials.gov Identifier: NCT05077579    
Other Study ID Numbers: 202102186
First Posted: October 14, 2021    Key Record Dates
Last Update Posted: February 21, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Alzheimer Disease
Obesity
Metabolic Diseases
Overweight
Overnutrition
Nutrition Disorders
Body Weight
Dementia
 Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders