PrediabetesTIMER2NCT07106450
Training Induced Muscle-Adipose EV Communication
A study testing Acute Resistance Exercise in people with Prediabetes, run by Yuan Wen at 1 site in United States.
Trial summary
This study examines how muscle cells communicate with fat cells through tiny packages called extracellular vesicles (EV) during exercise. These vesicles carry important molecules that may affect how the body processes sugar and fat. Read more about this study
- Who is it for?
- Ages 30 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Prediabetes
- What is being tested?
- Acute Resistance Exercise
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2026to 30 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 30 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age 30-55 years
- Sedentary lifestyle (exercise <1 day/week for at least 3 months prior to enrollment)
- Able to provide informed consent
- For Control Group: BMI < 27 kg/m², normal glucose tolerance, no more than 1 feature of metabolic syndrome
- For Prediabetic Group: BMI > 30 kg/m², at least 3 features of metabolic syndrome including prediabetes (defined as fasting plasma glucose 100-125 mg/dL OR 2-hour post-load glucose on 75g OGTT 140-199 mg/dL OR HbA1C 5.7-6.4%)
Who cannot join
- Pregnancy (confirmed by pregnancy test in women of childbearing potential)
- Type 2 diabetes mellitus
- Cardiovascular contraindications to resistance exercise
- Medical conditions that would interfere with muscle or adipose tissue biopsy procedures
- Use of medications that significantly affect glucose metabolism or exercise response
- Active participation in structured exercise programs (>1 day/week) within 3 months of enrollment
- Inability to safely participate in resistance exercise protocol
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Muscle-derived Extracellular Vesicles and Their Interactions With Adipocytes in Human Metabolic Dysfunction
This study examines how muscle cells communicate with fat cells through tiny packages called extracellular vesicles (EV) during exercise. These vesicles carry important molecules that may affect how the body processes sugar and fat. The research team observed significant variability in the adipose response to exercise, and used this variability to gain further insight into the mechanism through which mature microRNA-1 (miR-1) changes in adipose tissue. The investigators selected six subjects with the highest increase in miR-1 abundance in adipose tissue after exercise and compared them with the six subjects that had the most dramatic decrease in miR-1 abundance after exercise. The research team observed that participants intrinsically vary in their ability to endocytose EV into adipose tissue. It is unclear whether this variance in receptivity is a cause or consequence of the significant difference in EV-delivery of miR-1 to adipose tissue.
Read the detailed description
This study investigates muscle-derived extracellular vesicle (EV) communication with adipose tissue and how this pathway is altered in pre-diabetes. The investigators will recruit 40 participants (20 euglycemic controls, 20 pre-diabetic) aged 30-55 years, equally distributed by sex. Pre-diabetes will be defined as impaired fasting glucose (100-125 mg/dL), impaired glucose tolerance (2-hour oral glucose tolerance test (OGTT) 140-199 mg/dL), or HbA1C 5.7-6.4%.
Following informed consent and medical screening at the Center for Clinical and Translational Sciences, participants will undergo baseline blood draw and tissue biopsies (subcutaneous adipose and vastus lateralis muscle) one hour prior to exercise. The resistance exercise protocol consists of whole-body resistance training at 80% 1RM (repetition maximum) intensity including bench press, leg press, and pull-downs. Blood samples will be collected immediately post-exercise and at 30, 60, and 90 minutes. Post-exercise biopsies will be obtained approximately 60 minutes after exercise cessation.
Laboratory analyses will include: (1) microRNA-1 (miR-1) quantification in adipose tissue by quantitative reverse transcription polymerase chain reaction (qRT-PCR) as the primary validated outcome of EV uptake; (2) fluorescently-labeled EV uptake assessment in cultured adipocytes using microscopy; (3) RNA sequencing (RNA-seq) of adipose tissue to identify transcriptomic signatures associated with EV uptake capacity; (4) primary cell culture studies using adult-derived human adipocyte stem cells (ADHASC); and (5) EV isolation and characterization using size exclusion chromatography and density gradient centrifugation.
- Conditions
- Prediabetes
- Being tested
- Acute Resistance Exercise
- Keywords
- muscle, extracellular vesicles, adipose
- Medical subject headings
- Prediabetic State
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute Resistance ExerciseBehavioural
Also called Strength Training
Participants will perform three sets of eight repetitions, with a 90-120 second rest between sets, with a fourth set performed to failure. All resistance exercise will be performed on pneumatic resistance devices (Keiser Sports Health Equipment, Fresno, CA).
| Study group | Role | What they receive |
|---|---|---|
| Acute Resistance Exercise | Experimental | Participants will perform four exercises: squat, knee extension, leg press, and lat pulldown at 80% of 1-RM (repetition maximum) determined during a previous visit. Receives: Behavioral: Acute Resistance Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
miR-1 abundance in adipose tissue
Quantification of mature microRNA-1 levels in subcutaneous adipose tissue biopsies using quantitative Real Time-PCR as validated biomarker of in vivo extracellular vesicle uptake
Measured: 60 minutes post-exercise (single measurement)
Extracellular vesicle uptake capacity in primary adipocytes
Measurement of fluorescently-labeled extracellular vesicle internalization in cultured primary adipocytes using confocal microscopy to quantify uptake rates in units of vesicles per minute per cell.
Measured: 24-48 hours post-isolation (in vitro culture)
Secondary outcomes (4)
Serum extracellular vesicle miR-1 content
Time-course analysis of microRNA-1 abundance in isolated serum extracellular vesicles using quantitative RT-PCR to track temporal dynamics of muscle-derived vesicle release
Measured: Baseline, 0, 30, 60, and 90 minutes post-exercise
Adipose tissue transcriptomic signatures
RNA-sequencing analysis of subcutaneous adipose tissue to identify differential gene expression patterns associated with high versus low extracellular vesicle uptake capacity, focusing on endocytotic pathways
Measured: 60 minutes post-exercise (single measurement)
Adrenergic receptor gene expression in adipose tissue
Quantitative RT-PCR measurement of ADRβ1, ADRβ2, and ADRβ3 receptor mRNA levels in subcutaneous adipose tissue as downstream targets of miR-1 delivery
Measured: 60 minutes post-exercise (single measurement)
Primary muscle miR-1 transcript levels
Quantification of pri-miR-1a and pri-miR-1b primary transcript abundance in vastus lateralis muscle biopsies using quantitative RT-PCR to assess exercise-induced miR-1 biogenesis
Measured: 60 minutes post-exercise (single measurement)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Aug 2025
- Study startNov 2026 (estimated)
- Primary completion30 Sep 2028 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PrediabetesStudies of the same condition, open and under way.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Yuan Wen
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Responsible party
- Sponsor-investigator, Yuan Wen, University of Kentucky
- Investigators
- Yuan Wen, MD, PhD, Principal investigator, University of Kentucky
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07106450
- Sponsor's protocol ID
- P20GM156679-Prj5
- Other IDs
- P20GM156679
- Acronym
- TIMER2
- Status last verified
- Sep 2026
- First submitted
- 22 Jul 2025
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared to protect participant privacy and confidentiality. Summary results and findings will be made available through peer-reviewed publications and presentation at scientific conferences.
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Muscle-derived Extracellular Vesicles and Their Interactions With Adipocytes in Human Metabolic Dysfunction
- ClinicalTrials.gov ID
- NCT07106450
- Acronym / sponsor ID
- TIMER2 / P20GM156679-Prj5
- Conditions
- Prediabetes
- Keywords
- muscle, extracellular vesicles, adipose
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Yuan WenUniversity, hospital or other
- Collaborators
- National Institute of General Medical Sciences (NIGMS)
- Study start
- Nov 2026 (estimated)
- Primary completion
- 30 Sep 2028 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 6 Aug 2025 (actual)
- Results
- Not posted in the source record
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 how muscle cells communicate with fat cells through tiny packages called extracellular vesicles (EV) during exercise. These vesicles carry important molecules that may affect how the body processes sugar and fat. The research team observed significant variability in the adipose response to exercise, and used this variability to gain further insight into the mechanism through which mature microRNA-1 (miR-1) changes in adipose tissue. The investigators selected six subjects with the highest increase in miR-1 abundance in adipose tissue after exercise and compared them with the six subjects that had the most dramatic decrease in miR-1 abundance after exercise. The research team observed that participants intrinsically vary in their ability to endocytose EV into adipose tissue. It is unclear whether this variance in receptivity is a cause or consequence of the significant difference in EV-delivery of miR-1 to adipose tissue.
Detailed description
This study investigates muscle-derived extracellular vesicle (EV) communication with adipose tissue and how this pathway is altered in pre-diabetes. The investigators will recruit 40 participants (20 euglycemic controls, 20 pre-diabetic) aged 30-55 years, equally distributed by sex. Pre-diabetes will be defined as impaired fasting glucose (100-125 mg/dL), impaired glucose tolerance (2-hour oral glucose tolerance test (OGTT) 140-199 mg/dL), or HbA1C 5.7-6.4%.
Following informed consent and medical screening at the Center for Clinical and Translational Sciences, participants will undergo baseline blood draw and tissue biopsies (subcutaneous adipose and vastus lateralis muscle) one hour prior to exercise. The resistance exercise protocol consists of whole-body resistance training at 80% 1RM (repetition maximum) intensity including bench press, leg press, and pull-downs. Blood samples will be collected immediately post-exercise and at 30, 60, and 90 minutes. Post-exercise biopsies will be obtained approximately 60 minutes after exercise cessation.
Laboratory analyses will include: (1) microRNA-1 (miR-1) quantification in adipose tissue by quantitative reverse transcription polymerase chain reaction (qRT-PCR) as the primary validated outcome of EV uptake; (2) fluorescently-labeled EV uptake assessment in cultured adipocytes using microscopy; (3) RNA sequencing (RNA-seq) of adipose tissue to identify transcriptomic signatures associated with EV uptake capacity; (4) primary cell culture studies using adult-derived human adipocyte stem cells (ADHASC); and (5) EV isolation and characterization using size exclusion chromatography and density gradient centrifugation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute Resistance Exercise | Experimental | Behavioral: Acute Resistance ExerciseParticipants will perform four exercises: squat, knee extension, leg press, and lat pulldown at 80% of 1-RM (repetition maximum) determined during a previous visit. |
Who may qualify
- Ages
- 30 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age 30-55 years
- Sedentary lifestyle (exercise <1 day/week for at least 3 months prior to enrollment)
- Able to provide informed consent
- For Control Group: BMI < 27 kg/m², normal glucose tolerance, no more than 1 feature of metabolic syndrome
- For Prediabetic Group: BMI > 30 kg/m², at least 3 features of metabolic syndrome including prediabetes (defined as fasting plasma glucose 100-125 mg/dL OR 2-hour post-load glucose on 75g OGTT 140-199 mg/dL OR HbA1C 5.7-6.4%)
Key exclusion criteria (7 listed)
- Pregnancy (confirmed by pregnancy test in women of childbearing potential)
- Type 2 diabetes mellitus
- Cardiovascular contraindications to resistance exercise
- Medical conditions that would interfere with muscle or adipose tissue biopsy procedures
- Use of medications that significantly affect glucose metabolism or exercise response
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 |
|---|---|---|
| Acute Resistance ExerciseAlso: Strength TrainingParticipants will perform three sets of eight repetitions, with a 90-120 second rest between sets, with a fourth set performed to failure. All resistance exercise will be performed on pneumatic resistance devices (Keiser Sports Health Equipment, Fresno, CA). | Behavioural | Acute Resistance Exercise |
Primary outcome
miR-1 abundance in adipose tissue
Time frame: 60 minutes post-exercise (single measurement)
Quantification of mature microRNA-1 levels in subcutaneous adipose tissue biopsies using quantitative Real Time-PCR as validated biomarker of in vivo extracellular vesicle uptake
Extracellular vesicle uptake capacity in primary adipocytes
Time frame: 24-48 hours post-isolation (in vitro culture)
Measurement of fluorescently-labeled extracellular vesicle internalization in cultured primary adipocytes using confocal microscopy to quantify uptake rates in units of vesicles per minute per cell.
4 secondary outcomes
Serum extracellular vesicle miR-1 content
Time frame: Baseline, 0, 30, 60, and 90 minutes post-exercise
Adipose tissue transcriptomic signatures
Time frame: 60 minutes post-exercise (single measurement)
Adrenergic receptor gene expression in adipose tissue
Time frame: 60 minutes post-exercise (single measurement)
Primary muscle miR-1 transcript levels
Time frame: 60 minutes post-exercise (single measurement)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Individual participant dataSharing planned: No. Individual participant data will not be shared to protect participant privacy and confidentiality. Summary results and findings will be made available through peer-reviewed publications and presentation at scientific conferences.
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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.
Yuan Wen, MD, PhD principal investigator
University of Kentucky
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute Resistance Exercise in people with Prediabetes, run by Yuan Wen 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 5 inclusion and 7 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: opening soon, as of the sponsor's last update on 2 Oct 2026. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yuan Wen, MD/PhD (18592187185, ywen2@uky.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
miR-1 abundance in adipose tissue (time frame: 60 minutes post-exercise (single measurement)). The study lists 2 primary outcomes in all. 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 2 Oct 2026.