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

A Study of Adipose Tissue in Adaptive Responses to Exercise

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: NCT06053125
Recruitment Status : Recruiting
First Posted : September 25, 2023
Last Update Posted : December 5, 2023
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Hawley E. Kunz, Mayo Clinic

Tracking Information
First Submitted Date  ICMJE September 7, 2023
First Posted Date  ICMJE September 25, 2023
Last Update Posted Date December 5, 2023
Actual Study Start Date  ICMJE November 9, 2023
Estimated Primary Completion Date October 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 19, 2023)
  • Adipose Immune Cell Populations [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    The numbers of lymphocytes, monocytes, macrophages, and natural killer (NK) cells in the adipose tissue will be assessed by flow cytometry.
  • Inflammatory proteins secreted from adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins) [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    The concentrations of 96 different inflammatory proteins (including various cytokines and adipokines) will be measured using the targeted inflammation Olink proximity extension assay panel in media obtained from cultured adipose tissue explants. Adipose tissue samples will be cultured for 3 hours, and the culture media will be removed for the assessment of 96 different secreted inflammatory proteins. The Olink assay measures all 96 proteins in a single assay and all are reported as normalized protein expression values.
  • Adipose tissue macrophage populations [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Numbers of macrophages in the adipose tissue will be assessed by immunohistochemistry.
  • Adipose tissue gene expression of interleukin (IL)-6 measured by polymerase chain reaction (PCR). [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the inflammatory cytokine IL-6 will be measured in adipose tissue samples using real time (RT)-PCR.
  • Adipose tissue gene expression of interleukin (IL)-8 measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the inflammatory cytokine IL-8 will be assessed in adipose tissue samples using real-time (RT)-PCR.
  • Adipose tissue gene expression of cluster of differentiation 68 (CD68) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the macrophage marker CD68 be assessed in adipose tissue samples using real time (RT)-PCR.
  • Adipose tissue gene expression of cluster of differentiation 163 (CD163) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the anti-inflammatory macrophage marker CD163 will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of cluster of differentiation 206 (CD206) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the anti-inflammatory macrophage marker CD206 will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of adhesion G-protein coupled receptor E (ADGRE) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the macrophage marker ADGRE will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of inducible nitric oxide synthase (INOS) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the pro-inflammatory macrophage marker INOS will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of monocyte chemoattractant protein-1 (MCP1) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the inflammatory cytokine MCP1 will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of tumor necrosis factor alpha (TNFa) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the inflammatory cytokine TNFa will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of leptin (LEPD) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the pro-inflammatory adipokine LEPD will be assessed in adipose tissue samples using RT-PCR.
  • Adipose tissue gene expression of adiponectin (ADIPOQ) measured by PCR. [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Gene expression of the anti-inflammatory adipokine ADIPOQ will be assessed in adipose tissue samples using RT-PCR.
  • Inflammatory proteins found in adipose tissue measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins) [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    The concentrations of 96 different inflammatory proteins (including various cytokines and adipokines) will be measured in adipose tissue lysates using the targeted inflammation Olink proximity extension assay panel. This assay measures all 96 proteins in a single assay and all are reported as normalized protein expression values.
  • Protein cargo of adipose extracellular vesicles measured using mass spectrometry [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Adipose tissue samples will be cultured for 3 hours, and the culture media will be removed. From this media, extracellular vesicles will be isolated. In these extracellular vesicles, mass spectrometry will be performed to examine the entire proteome (all proteins) contained within these extracellular vesicles. Using the large number of proteins identified, the investigators will examine changes in categories of protein types (e.g., inflammatory proteins, metabolic proteins, transcriptional proteins).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 19, 2023)
  • Adipocyte cell size [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Adipocyte cell size will be determined using methylene blue staining and microscopy.
  • Plasma inflammatory cytokine concentrations measured using the Olink Target Inflammation Panel (includes 96 inflammation-associated proteins) [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    The concentrations of 96 different inflammatory proteins (including various cytokines and adipokines) will be measured in plasma samples using the targeted inflammation Olink proximity extension assay panel. This assay measures all 96 proteins in a single assay and all are reported as normalized protein expression values.
  • Protein cargo of plasma extracellular vesicles measured using mass spectrometry extracellular vesicles [ Time Frame: Pre-exercise, immediately post-exercise, and 3 hours after exercise ]
    Extracellular vesicles will be isolated from plasma samples. In these extracellular vesicles, mass spectrometry will be performed to examine the entire proteome (all proteins) contained within these extracellular vesicles. Using the large number of proteins identified, the investigators will examine changes in categories of protein types (e.g., inflammatory proteins, metabolic proteins, transcriptional proteins).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: September 19, 2023)
  • Body fat percentage [ Time Frame: Baseline ]
    Body fat percentage will be assessed using dual energy x-ray absorptiometry (DEXA).
  • Cardiorespiratory Fitness [ Time Frame: Baseline ]
    Individual maximal oxygen consumption (VO2 max) will be assessed by indirect calorimetry during a graded exercise test
  • White blood count [ Time Frame: Baseline ]
    White blood count with differential will be measured by the Mayo clinical lab.
  • Fasting plasma insulin [ Time Frame: Baseline ]
    Plasma insulin will be measured by the Mayo Clinical Lab.
  • Fasting plasma glucose [ Time Frame: Baseline ]
    Plasma glucose will be measured by the Mayo Clinical Lab.
  • Hemoglobin A1c (HbA1c) [ Time Frame: Baseline ]
    HbA1c will be measured by the Mayo Clinical Lab.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE A Study of Adipose Tissue in Adaptive Responses to Exercise
Official Title  ICMJE The Role of Adipose Tissue in Adaptive Responses to Exercise
Brief Summary The purpose of this research is to determine how exercise affects fat (adipose) tissue and how changes to adipose tissue that occur during and after exercise might improve health in aging and obesity.
Detailed Description

Adipose tissue has important endocrine functions that influence metabolic health. Early evidence shows that adipose adapts to physiological stress, including exercise. The objective here is to determine how exercise-induced alterations in adipose tissue cellular composition and endocrine signaling may contribute to the beneficial adaptations to exercise in aging and obesity.

Immune cell populations and inflammatory signatures will be assessed in subcutaneous abdominal adipose tissue biopsies collected from obese and normal weight young and older adults before, immediately after, and 3 hours after a 30-min bout of cycling exercise at 70% of maximal oxygen consumption (VO2max). Mass spectrometry, Olink targeted inflammation assays, and RNA sequencing will be used for full proteomic and transcriptomic characterization of the adipose tissue secretome (the proteins and molecules secreted from the adipose tissue) and the cargo of extracellular vesicles isolated from plasma and media collected from cultured human adipose tissue explants generated from each time point.

Overall, the primary hypothesis of the proposed work is that a single bout of exercise triggers transient changes in adipose tissue paracrine/endocrine signals and immune cellular composition. The investigators propose that these responses contribute to the beneficial effects of exercise locally and in distal tissues and that the cumulative effects of acute changes in adipose tissue likely contribute to the positive alterations in adipose tissue associated with exercise training.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE
  • Healthy
  • Obesity
Intervention  ICMJE
  • Procedure: Adipose Tissue Biopsy
    Fat sample collected from abdomen before exercise, immediately after exercise, and 3 hours after exercise
  • Behavioral: Exercise
    30 minutes of exercise on a cycle ergometer exercise machine
Study Arms  ICMJE
  • Experimental: Older adults with obesity
    Participants with a body mass index (BMI) between 30 and 40 and aged 65-85 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
    Interventions:
    • Procedure: Adipose Tissue Biopsy
    • Behavioral: Exercise
  • Experimental: Older adults without obesity
    Participants with a BMI between 18.5 and 28 and aged 65-85 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
    Interventions:
    • Procedure: Adipose Tissue Biopsy
    • Behavioral: Exercise
  • Experimental: Young adults with obesity
    Participants with a BMI between 30 and 40 and aged 18-35 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
    Interventions:
    • Procedure: Adipose Tissue Biopsy
    • Behavioral: Exercise
  • Experimental: Young adults without obesity
    Participants with a BMI between 18.5 and 28 and aged 18-35 years will have an adipose tissue biopsy taken from the abdomen before and after exercise.
    Interventions:
    • Procedure: Adipose Tissue Biopsy
    • Behavioral: Exercise
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 19, 2023)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2026
Estimated Primary Completion Date October 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Adults between the ages of 18-35 OR 65-85.
  • BMI <28 kg/m2 or BMI between 30 kg/m2 and 40 kg/m2
  • Weight stable (≥ 3 months)
  • Generally healthy

Exclusion Criteria:

  • Participation in ≥ 30 minutes of structured physical activity ≥ 2 days per week.
  • Smoking/tobacco use.
  • Alcohol/substance abuse.
  • Pregnancy and breastfeeding.
  • Anemia.
  • Abnormal renal function.
  • Blood clotting disorders.
  • Coronary artery disease.
  • Uncontrolled thyroid disease.
  • Liver disease.
  • Use of medications known to influence the main outcomes of the study.
  • Orthopedic problems that may be aggravated by exercise.
  • Chronic disease at the discretion of the investigators.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Rose Decker 507-255-6770 bilderback.rose@mayo.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT06053125
Other Study ID Numbers  ICMJE 23-002049
K01DK134765 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Hawley E. Kunz, Mayo Clinic
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Mayo Clinic
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators  ICMJE
Principal Investigator: Hawley Kunz, PhD Mayo Clinic
PRS Account Mayo Clinic
Verification Date December 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP