Diabetes Mellitus, Type 2NCT03534687
Exercise and the Receptor for Advanced Glycation End Products (RAGE)
A study testing Aerobic Exercise in people with Diabetes Mellitus, Type 2, run by University of Michigan at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Aerobic Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Dec 2018to 8 May 2023
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 40-75 y
- Type 2 diabetes
- Overweight or obese (BMI 26-44 kg/m2)
- Fluency in English (written and verbal)
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Exercise in the Prevention and Treatment of RAGE-Mediated Inflammation (RECEPTOR) Trial
This study examines the effects of 12-weeks of aerobic exercise training on the mechanisms driving RAGE-mediated inflammation in type 2 diabetic humans.
Read the 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.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Aerobic Exercise
- Keywords
- RAGE, ADAM10, Exercise, sRAGE
- Medical subject headings
- Diabetes Mellitus, Type 2, Alzheimer Disease 10, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Aerobic ExerciseBehavioural
12-week supervised aerobic exercise
| Study group | Role | What they receive |
|---|---|---|
| Aerobic Exercise Group | Experimental | Aerobic Exercise (AE) subjects will come in for supervised, aerobic exercise training sessions 5 days a week for 12 weeks. Training will progress from 55% VO2max for week 1 (40 min session), to 60-65% VO2max for week 2 (50 min session), to ~70% VO2max for all other weeks (50 min session). Subjects will perform a warm-up and cool down (~5 min each) that includes stretching exercises. Subjects will wear heart rate monitors during each training session to provide feedback of target heart rate. Intensity, duration, resting and exercise heart rates, and blood pressures will be recorded for each session. Follow-up VO2max tests will be performed at weeks 4 and 8 to monitor progress and adjust AE training intensity. Receives: Behavioral: Aerobic Exercise |
| Control Group | No intervention | During the 12 week control period, subjects are to maintain their normal, daily-living activities. Control group participants will be given the option to enroll in the AE training group after completion of the original Control group trial period. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Quantify the Percentage Change in Basal Circulating sRAGE After 12-weeks of Supervised Aerobic Exercise Training.
Serum will be separated from blood samples collected in vacutainer tubes via centrifugation before and after 12-weeks of aerobic exercise training. sRAGE will be quantified in these serum samples via ELISA (Quantikine, Human RAGE Immunoassay) per manufacture's protocol.
Measured: Baseline and 12 weeks
Secondary outcomes (3)
Quantify the Percentage Change in Basal Muscle RAGE Expression After 12-weeks of Supervised Aerobic Exercise Training.
Basal biopsy derived skeletal muscle RAGE expression will be determined from the vastus lateralis before and after 12-weeks of aerobic exercise training. RAGE expression will be quantified via Western Blot. Muscle samples (~10 mg) will be homogenized and protein concentration will be determined via BCA assay (Pierce). Samples (20 μg protein) will be diluted in SDS buffer, heated at 85 °C for 5 min, resolved via SDS-PAGE (Bio-Rad Laboratories, Hercules, CA) and transferred to a nitrocellulose or PVDF membrane. Blocking will occur for 1 h and primary antibody (RAGE; Abcam, Cambridge, MA) incubation will occur overnight at 4 °C and quantified vs a standard or total protein.
Measured: Baseline and 12 weeks
Quantify the Percentage Change in Aerobic Capacity (VO2max) After 12-weeks of Supervised Aerobic Exercise Training.
Maximal oxygen consumption (VO2max) will be established via indirect calorimetry during an incremental treadmill test (Modified Bruce protocol) before and after 12-weeks of aerobic exercise training. Criteria, such as, rating of perceived exertion >18, respiratory exchange ratio >1.10, no further increase in VO2 despite increasing workloads, heart rate greater than age-predicted maximum, or volitional fatigue will be used to indicate a successful VO2max was achieved.
Measured: Baseline and 12 weeks
Quantify the Percentage Change in Insulin Sensitivity After 12-weeks of Supervised Aerobic Exercise Training.
Insulin sensitivity will be established via calculation of Matsuda Index from glucose and insulin values obtained every 30 minutes during a 75 g Oral GlucoseTolerance Test. Data are represented as percent change. Any change greater than a value of zero indicates an improvement in insulin sensitivity.
Measured: Baseline and 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2018
- Study start20 Dec 2018
- Primary completion8 May 2023
- Study completion8 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by University of MichiganThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jacob Haus, University of Michigan
- Investigators
- Jacob Haus, PhD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03534687
- Sponsor's protocol ID
- HUM00146001
- Other IDs
- 5R01DK109948-02
- Status last verified
- Jul 2024
- First submitted
- 11 May 2018
- Last updated
- 13 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Exercise in the Prevention and Treatment of RAGE-Mediated Inflammation (RECEPTOR) Trial
- ClinicalTrials.gov ID
- NCT03534687
- Acronym / sponsor ID
- HUM00146001
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- RAGE, ADAM10, Exercise, sRAGE
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 20 Dec 2018 (actual)
- Primary completion
- 8 May 2023 (actual)
- Study completion
- 8 May 2023 (actual)
- First posted
- 23 May 2018 (actual)
- Results
- Posted 13 Aug 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Aerobic Exercise Group | Experimental | Behavioral: Aerobic ExerciseAerobic Exercise (AE) subjects will come in for supervised, aerobic exercise training sessions 5 days a week for 12 weeks. Training will progress from 55% VO2max for week 1 (40 min session), to 60-65% VO2max for week 2 (50 min session), to ~70% VO2max for all other weeks (50 min session). Subjects will perform a warm-up and cool down (~5 min each) that includes stretching exercises. Subjects will wear heart rate monitors during each training session to provide feedback of target heart rate. Intensity, duration, resting and exercise heart rates, and blood pressures will be recorded for each session. Follow-up VO2max tests will be performed at weeks 4 and 8 to monitor progress and adjust AE training intensity. |
| Control Group | No intervention | –During the 12 week control period, subjects are to maintain their normal, daily-living activities. Control group participants will be given the option to enroll in the AE training group after completion of the original Control group trial period. |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 40-75 y
- Type 2 diabetes
- Overweight or obese (BMI 26-44 kg/m2)
- Fluency in English (written and verbal)
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Aerobic Exercise12-week supervised aerobic exercise | Behavioural | Aerobic Exercise Group |
Primary outcome
Quantify the Percentage Change in Basal Circulating sRAGE After 12-weeks of Supervised Aerobic Exercise Training.
Time frame: Baseline and 12 weeks
Serum will be separated from blood samples collected in vacutainer tubes via centrifugation before and after 12-weeks of aerobic exercise training. sRAGE will be quantified in these serum samples via ELISA (Quantikine, Human RAGE Immunoassay) per manufacture's protocol.
3 secondary outcomes
Quantify the Percentage Change in Basal Muscle RAGE Expression After 12-weeks of Supervised Aerobic Exercise Training.
Time frame: Baseline and 12 weeks
Quantify the Percentage Change in Aerobic Capacity (VO2max) After 12-weeks of Supervised Aerobic Exercise Training.
Time frame: Baseline and 12 weeks
Quantify the Percentage Change in Insulin Sensitivity After 12-weeks of Supervised Aerobic Exercise Training.
Time frame: Baseline and 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jacob Haus, PhD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Aerobic Exercise in people with Diabetes Mellitus, Type 2, run by University of Michigan at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Quantify the Percentage Change in Basal Circulating sRAGE After 12-weeks of Supervised Aerobic Exercise Training. (time frame: Baseline and 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2024; AzTrials last refreshed its copy on 6 Nov 2026.