Clinical trial NCT03534687: Exercise and the Receptor for Advanced Glycation End Products (RAGE)
Official title: Role of Exercise in the Prevention and Treatment of RAGE-Mediated Inflammation (RECEPTOR) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Diabetes Mellitus, Type 2
Keywords: RAGE
ADAM10
Exercise
sRAGE
Lead sponsor: University of Michigan
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2018-05-23
Enrollment: 50
Sex: ALL
Minimum age (years): 40
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study examines the effects of 12-weeks of aerobic exercise training on the mechanisms driving RAGE-mediated inflammation in type 2 diabetic humans.

Detailed description: Activation of RAGE (receptor of advanced glycation endproducts (AGEs)), via binding of AGEs and other ligands, modulates the development and progression of diabetic complications through persistent and cyclic activation of nuclear factor-kappa beta. Targeting RAGE directly as a therapeutic strategy has largely been unsuccessful. However, RAGE signaling can be interrupted, in vivo, by ADAM10 (a disintegrin and metalloproteinase 10) directed proteolytic cleavage of the RAGE ectodomain, and thus creating a soluble isoform of RAGE (sRAGE) that is released from the cell and appears into the circulation. Maintaining high levels of circulating sRAGE is advantageous as sRAGE will sequester RAGE ligands and prevent RAGE cell signaling.

Although the exact mechanisms of ADAM10 mediated RAGE release remain undefined, calcium related and other signaling (SIRT1) impact ADAM10. Aerobic exercise presents a unique model for mechanistic study of RAGE release as muscle contraction induces robust calcium signaling, activates SIRT1, and provides stimuli for tissue remodeling and resolution of the metabolic profile that drives inflammation.

Eligibility criteria: Inclusion Criteria:

* Age 40-75 y
* Type 2 diabetes
* Overweight or obese (BMI 26-44 kg/m2)
* Fluency in English (written and verbal)

Exclusion Criteria:

* Age \<40 or \>75 y
* BMI \<26 or \>44 kg/m2
* Existing cardiovascular, cerebrovascular, renal, or hematological disease, or cancer
* Current use of tobacco
* Pregnant or lactating
* Medications that may interfere with study outcomes

Primary outcomes:
measure: Quantify the Percentage Change in Basal Circulating sRAGE After 12-weeks of Supervised Aerobic Exercise Training.
timeFrame: Baseline and 12 weeks
Secondary outcomes:
measure: Quantify the Percentage Change in Basal Muscle RAGE Expression After 12-weeks of Supervised Aerobic Exercise Training.
timeFrame: Baseline and 12 weeks
measure: Quantify the Percentage Change in Aerobic Capacity (VO2max) After 12-weeks of Supervised Aerobic Exercise Training.
timeFrame: Baseline and 12 weeks
measure: Quantify the Percentage Change in Insulin Sensitivity After 12-weeks of Supervised Aerobic Exercise Training.
timeFrame: Baseline and 12 weeks
Other outcomes:
Locations:
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: University of Michigan
name: Jacob Haus, PhD
role: PRINCIPAL_INVESTIGATOR
References: