Pre-diabetesNCT04442451
Mechanisms of Fatigability With Diabetes
A study testing Blood Flow Restriction Exercise in people with Pre-diabetes and Type 2 Diabetes, run by University of Michigan at 1 site in United States.
Trial summary
Pre-diabetes (Pre-D) is a precursor to type 2 diabetes (T2D) and characterized by increased exercise fatigability of lower limb muscles, that can impede exercise performance. The cause for the increased fatigability in people with Pre-D is not known. Read more about this study
- Who is it for?
- Ages 30 to 85 years
- Conditions the study is for
- Pre-diabetes, Type 2 Diabetes
- What is being tested?
- Blood Flow Restriction Exercise
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2022to 31 Aug 2027
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women adults 30 years to 85 years or less
- Pre-diabetes [glycosylated hemoglobin (HbA1c) of 5.7-6.4% and fasting plasma glucose 100-125 mg/dL at the time of initial screening]
- Controls [normoglycemic with a HbA1c level ≤5.6% and fasting blood glucose ≤ 99 mg/dL (5.5 mmol/L)]
- Type 2 Diabetes Mellitus [elevated glycosylated hemoglobin (HbA1c) >6.5% and <10%]
Who cannot join
- Signs or symptoms of neuropathy
- Medications associated with advanced stages of T2D including insulin
- Poor glycemic control (HbA1c>10%)
- Peripheral edema
- Severe obesity (BMI, >45kg·m-2)
- Untreated hypothyroidism
Show all 10Show fewer
- Smoking
- Hypertension
- Cardiovascular or musculoskeletal disease that preclude exercise testing
- Hormone replacement drugs or vasoactive medications
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Sarah Lessila, MSc contact
United States1 site, 1 recruiting
- Recruiting
University of Michigan
Ann Arbor, Michigan, 48109
Sandra Hunter, PhD, (734) 647-9819, sandrahu@umich.edu
Sarah Lessila, MS, (734) 647-6019, slessila@umich.edu
About this study
Official title: Mechanisms of Fatigability and the Protective Effects of Exercise in People With Diabetes
Pre-diabetes (Pre-D) is a precursor to type 2 diabetes (T2D) and characterized by increased exercise fatigability of lower limb muscles, that can impede exercise performance. The cause for the increased fatigability in people with Pre-D is not known. Given the profound vascular disease present in people who have had uncontrolled diabetes for several years, we will determine whether dynamic, fatiguing contractions of the lower limb muscles in people with Pre-D are limited by vascular dysfunction at multiple levels along the vascular tree including the artery, arteriole, and/or capillary. This clinical trial involves a novel exercise training regime involving blood flow restriction to the exercising limb will be used as a probe to further understand the vascular mechanisms for increased fatigability in people with Pre-D and T2D. The long-term goal is to better understand what limits exercise and functional performance in people with diabetes to help develop targeted, more effective exercise programs.
Read the detailed description
The aim of the clinical trial is to determine the effectiveness of dynamic resistance exercise training coupled with blood flow restriction to improve fatigability and vascular function in people with Pre-D and T2D. People with Pre-D and T2D from Aim 1 will perform 8 weeks of dynamic unilateral resistance exercise training in which one leg is exercised with freely perfused conditions and the other leg with blood flow restriction.
We will assess fatigability, skeletal muscle metabolism, capillary density, and vascular function in people with Pre-D and T2D before and after a novel training intervention that couples dynamic resistance training with blood flow restriction to the exercising limb. This novel intervention has been shown to improve vascular function in young and older adults but has not been investigated in people with Pre-D and T2D. Endothelial function in intact large conduit arteries and arterioles isolated from skeletal muscle biopsies will be measured before and after the training intervention to assess whether the novel training improves vascular function along multiple levels of the vascular tree in people with Pre-D and T2D. Skeletal muscle blood flow through the femoral artery will be quantified with Doppler ultrasonography and skeletal muscle oxygenation will be measured with near infrared spectroscopy (NIRS) during a dynamic fatiguing knee extension exercise. We will closely match participant groups for physical activity levels, age, sex, and body mass index (BMI), because these confounders are not typically controlled for in other human studies.
- Conditions
- Pre-diabetes, Type 2 Diabetes
- Being tested
- Control Exercise, Blood Flow Restriction Exercise
- Keywords
- Diabetes, Pre-diabetes, Fatigability, Blood Flow Restriction Training, Vascular Function, Muscle Fatigue
- Medical subject headings
- Glucose Intolerance, Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Control ExerciseOther
Each participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) without blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions.
Blood Flow Restriction ExerciseOther
Each participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) with blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions.
| Study group | Role | What they receive |
|---|---|---|
| Control Exercise | Experimental | Low-load knee extension resistance training (20% of 1-RM) without blood flow restriction. A 10-cm wide inflatable cuff will be placed around the upper portion of the thigh but not inflated. Receives: Other: Control Exercise |
| Blood Flow Restriction Exercise | Experimental | Low-load knee extension resistance training (20% of 1-RM) with blood flow restriction using a 10-cm wide inflatable cuff placed around the most proximal part of the exercising thigh. Blood flow will be restricted in the BFR leg at above the limb occlusion pressure of the and this will be determined prior to the exercise while the participant is seated in the knee extensor machine. The cuff pressure during the BFR protocol will be 10 mmHg above limb occlusion pressure. Receives: Other: Blood Flow Restriction Exercise |
What is being measured
The primary outcome is the main question the study is designed to answer.
Fatigability - Reduction in Power
Reduction in limb power and maximal force in response to a dynamic fatiguing contraction.
Measured: One session before and then after 8 weeks of training
Strength - 1 Repetition Maximum
Reduction in limb power and maximal force in response to a dynamic fatiguing contraction
Measured: One session before and then after 8 weeks of training
Strength - Maximal Voluntary Contraction (MVC)
Changes in MVC after 8 weeks resistance training. MVC is the greatest force generated during a brief isometric contraction.
Measured: One session before and then after 8 weeks of training
Leg Blood Flow
Femoral artery mean blood velocity and femoral artery diameter will be measured using Doppler ultrasonography before and immediately after the fatiguing task in each leg.
Measured: One session before and then after 8 weeks of training
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2020
- Study start1 Sep 2022
- Primary completion1 Jul 2027 (estimated)
- Study completion31 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pre-diabetesStudies 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
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each participant will attend 3 sessions per week for 8 weeks. A training session will start with a 10-minute warm up on a bike ergometer. Each leg will then perform low-load resistance training (\~20% of 1-RM) for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions while seated in a knee extension weight machine. One leg will be randomized to always perform the training with blood flow restriction (BFR leg) while the contralateral leg performs the exercise training without blood flow occlusion (Control leg).
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Michigan
- Sponsor type
- University, hospital or other
- Collaborators
- University of Illinois Chicago, Medical College of Wisconsin, University of Wisconsin, Madison, National Institute on Aging (NIA), Marquette University
- Responsible party
- Principal investigator, Sandra Hunter, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04442451
- Sponsor's protocol ID
- HUM00255375
- Other IDs
- 5R01AG077688-03
- Status last verified
- Oct 2025
- First submitted
- 18 Jun 2020
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No data will be shared
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Fatigability and the Protective Effects of Exercise in People With Diabetes
- ClinicalTrials.gov ID
- NCT04442451
- Acronym / sponsor ID
- HUM00255375
- Conditions
- Pre-diabetes, Type 2 Diabetes
- Keywords
- Diabetes, Pre-diabetes, Fatigability, Blood Flow Restriction Training, Vascular Function, Muscle Fatigue
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of MichiganUniversity, hospital or other
- Collaborators
- University of Illinois Chicago, Medical College of Wisconsin, University of Wisconsin, Madison, National Institute on Aging (NIA), Marquette University
- Study start
- 1 Sep 2022 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 31 Aug 2027 (estimated)
- First posted
- 22 Jun 2020 (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.
Pre-diabetes (Pre-D) is a precursor to type 2 diabetes (T2D) and characterized by increased exercise fatigability of lower limb muscles, that can impede exercise performance. The cause for the increased fatigability in people with Pre-D is not known. Given the profound vascular disease present in people who have had uncontrolled diabetes for several years, we will determine whether dynamic, fatiguing contractions of the lower limb muscles in people with Pre-D are limited by vascular dysfunction at multiple levels along the vascular tree including the artery, arteriole, and/or capillary. This clinical trial involves a novel exercise training regime involving blood flow restriction to the exercising limb will be used as a probe to further understand the vascular mechanisms for increased fatigability in people with Pre-D and T2D. The long-term goal is to better understand what limits exercise and functional performance in people with diabetes to help develop targeted, more effective exercise programs.
Detailed description
The aim of the clinical trial is to determine the effectiveness of dynamic resistance exercise training coupled with blood flow restriction to improve fatigability and vascular function in people with Pre-D and T2D. People with Pre-D and T2D from Aim 1 will perform 8 weeks of dynamic unilateral resistance exercise training in which one leg is exercised with freely perfused conditions and the other leg with blood flow restriction.
We will assess fatigability, skeletal muscle metabolism, capillary density, and vascular function in people with Pre-D and T2D before and after a novel training intervention that couples dynamic resistance training with blood flow restriction to the exercising limb. This novel intervention has been shown to improve vascular function in young and older adults but has not been investigated in people with Pre-D and T2D. Endothelial function in intact large conduit arteries and arterioles isolated from skeletal muscle biopsies will be measured before and after the training intervention to assess whether the novel training improves vascular function along multiple levels of the vascular tree in people with Pre-D and T2D. Skeletal muscle blood flow through the femoral artery will be quantified with Doppler ultrasonography and skeletal muscle oxygenation will be measured with near infrared spectroscopy (NIRS) during a dynamic fatiguing knee extension exercise. We will closely match participant groups for physical activity levels, age, sex, and body mass index (BMI), because these confounders are not typically controlled for in other human studies.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Each participant will attend 3 sessions per week for 8 weeks. A training session will start with a 10-minute warm up on a bike ergometer. Each leg will then perform low-load resistance training (~20% of 1-RM) for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions while seated in a knee extension weight machine. One leg will be randomized to always perform the training with blood flow restriction (BFR leg) while the contralateral leg performs the exercise training without blood flow occlusion (Control leg).
| Arm | Type | Receives |
|---|---|---|
| Control Exercise | Experimental | Other: Control ExerciseLow-load knee extension resistance training (20% of 1-RM) without blood flow restriction. A 10-cm wide inflatable cuff will be placed around the upper portion of the thigh but not inflated. |
| Blood Flow Restriction Exercise | Experimental | Other: Blood Flow Restriction ExerciseLow-load knee extension resistance training (20% of 1-RM) with blood flow restriction using a 10-cm wide inflatable cuff placed around the most proximal part of the exercising thigh. Blood flow will be restricted in the BFR leg at above the limb occlusion pressure of the and this will be determined prior to the exercise while the participant is seated in the knee extensor machine. The cuff pressure during the BFR protocol will be 10 mmHg above limb occlusion pressure. |
Who may qualify
- Ages
- 30 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Men and women adults 30 years to 85 years or less
- Pre-diabetes [glycosylated hemoglobin (HbA1c) of 5.7-6.4% and fasting plasma glucose 100-125 mg/dL at the time of initial screening]
- Controls [normoglycemic with a HbA1c level ≤5.6% and fasting blood glucose ≤ 99 mg/dL (5.5 mmol/L)]
- Type 2 Diabetes Mellitus [elevated glycosylated hemoglobin (HbA1c) >6.5% and <10%]
Key exclusion criteria (10 listed)
- Signs or symptoms of neuropathy
- Medications associated with advanced stages of T2D including insulin
- Poor glycemic control (HbA1c>10%)
- Peripheral edema
- Severe obesity (BMI, >45kg·m-2)
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 |
|---|---|---|
| Control ExerciseEach participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) without blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions. | Other | Control Exercise |
| Blood Flow Restriction ExerciseEach participant will attend 3 sessions per week for 8 weeks. Participants will perform low-load knee extension resistance training (20% of 1-RM) with blood flow restriction on the designated leg for 4 sets of contractions with 15 contractions per set of contractions with a 30 second rest between each set of contractions. | Other | Blood Flow Restriction Exercise |
Primary outcome
Fatigability - Reduction in Power
Time frame: One session before and then after 8 weeks of training
Reduction in limb power and maximal force in response to a dynamic fatiguing contraction.
Strength - 1 Repetition Maximum
Time frame: One session before and then after 8 weeks of training
Reduction in limb power and maximal force in response to a dynamic fatiguing contraction
Strength - Maximal Voluntary Contraction (MVC)
Time frame: One session before and then after 8 weeks of training
Changes in MVC after 8 weeks resistance training. MVC is the greatest force generated during a brief isometric contraction.
Leg Blood Flow
Time frame: One session before and then after 8 weeks of training
Femoral artery mean blood velocity and femoral artery diameter will be measured using Doppler ultrasonography before and immediately after the fatiguing task in each leg.
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 1 Sep 2026.
- Individual participant dataSharing planned: No. No data will be shared
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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.
Sarah Lessila, MSc contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood Flow Restriction Exercise in people with Pre-diabetes and Type 2 Diabetes, 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 10 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: looking for participants now, as of the sponsor's last update on 1 Sep 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 Sandra Hunter, PhD ((734) 647-9819, sandrahu@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Fatigability - Reduction in Power (time frame: One session before and then after 8 weeks of training). The study lists 4 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 1 Sep 2026.