Type 1 DiabetesEarly Phase 1T-St1MNCT04449198
Type 1 Diabetes, Endothelin, and Skeletal Muscle Mitochondrial Dysfunction: The Role of Sirtuin-1
A Early Phase 1 study testing Resveratrol in people with Type 1 Diabetes, run by Augusta University at 1 site in United States.
Trial summary
The proposed study is designed to test the hypothesis that treatment of resveratrol for 12 weeks will improve both endothelin-B receptor (aim 1) and skeletal muscle mitochondrial function (aim 2) in people with type 1 diabetes. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Type 1 Diabetes
- What is being tested?
- Resveratrol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Oct 2020to 1 Jul 2027
- Phase
- Early Phase 1
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Men and premenopausal women
- All races
- Clinical diagnosis of insulin-dependent type 1 diabetes (patients only)
Who cannot join
- Clinical diagnosis of hepatic, cardiovascular, or renal disease
- Uncontrolled diabetes (HbA1C >12%)
- Diabetic complications (i.e. neuropathy)
- Uncontrolled hypertension (>140/90 mm Hg on therapy)
- Pregnancy
- Use of 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.
United States1 site, 1 recruiting
- Recruiting
Augusta University/Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology
Augusta, Georgia, 30912
Ryan Harris, PhD, CEP, 706-721-5998, ryharris@augusta.edu
Casey Derella, BS, 706-721-5483, cderella@augusta.edu
About this study
The proposed study is designed to test the hypothesis that treatment of resveratrol for 12 weeks will improve both endothelin-B receptor (aim 1) and skeletal muscle mitochondrial function (aim 2) in people with type 1 diabetes.
Read the detailed description
Preliminary data from the investigators' laboratory demonstrate a negative relationship between hemoglobin A1c (HbA1c) and ETBR function, supporting ETBR may be dysfunctional in the presence of T1D. Using near infrared spectroscopy (NIRS) to non-invasively assess muscle function, the investigators have also observed reduced skeletal muscle mitochondrial function in people with T1D compared to healthy controls. In addition, reduced circulating Sirt1 is associated with both ETBR and skeletal muscle mitochondrial dysfunction in the general population. For the current application, the investigators propose to utilize intradermal microdialysis and NIRS as unique, novel, and minimally invasive methods to investigate ETBR and skeletal muscle mitochondrial function, respectively, in people with T1D. Accordingly, the central hypothesis is that increasing circulating Sirt1 with oral supplementation of resveratrol will improve both ETBR function and mitochondrial skeletal muscle function, reducing overall CVD risk (Figure 1). The investigators will test this hypothesis with the following specific aims:
Aim 1: To test the hypothesis that an increase in Sirt1 will improve ETBR function in people with T1D. The investigators will evaluate ETBR function and circulating Sirt1 at baseline and after a 12-week treatment of resveratrol or placebo. Based on preliminary data, the investigators predict that people with T1D will have ETBR dysfunction compared to controls. In addition, the investigators predict that increasing Sirt1 following resveratrol treatment will improve ETBR function, whereas no change will occur with placebo.
Aim 2: To test the hypothesis that an increase in Sirt1 will improve skeletal muscle mitochondrial function and lower HbA1c in people with T1D. A non-invasive assessment of skeletal muscle function will be performed on people with T1D before and after 12-weeks of treatment with resveratrol or placebo. Compared to controls, the investigators predict that people with T1D will have skeletal muscle dysfunction. Following 12 weeks of resveratrol, the investigators predict that the increase in circulating Sirt1 will improve skeletal muscle function. Additionally, the investigators predict the improved skeletal muscle function will contribute to a subsequent decrease in HbA1c in people with T1D.
- Conditions
- Type 1 Diabetes
- Being tested
- Resveratrol, Placebo
- Keywords
- diabetes, heart disease, muscle function, blood vessels
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Heart Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ResveratrolDrug
500 mg of oral trans-resveratrol twice daily (in the morning and evening) for 12-weeks
PlaceboOther
placebo for 12 weeks
| Study group | Role | What they receive |
|---|---|---|
| Individuals with type 1 diabetes | Experimental | Individuals with type 1 diabetes will be randomly assigned to 1 of the 2 interventions (Resveratrol or placebo) Receives: Drug: Resveratrol; Other: Placebo |
| Healthy Controls | No intervention | Healthy individuals who participate will receive no intervention and serve as controls. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in AUC for ET-1 + BQ-123
Change in Area Under the Curve (AUC) for Cutaneous Vascular Conductance (CVC) in response to co-perfusion of ET-1 + BQ-123 at 12 weeks. Measured using intradermal microdialysis technique in conjunction with Laser Speckle Contrast Imaging (Moor FLPI-2) and beat-by-beat blood pressure monitoring (Finapres NOVA).
Measured: Measure taken at Baseline and post 12 weeks
Skeletal Muscle Mitochondrial Function
Change in Skeletal Muscle Mitochondrial Function at 12 weeks. Measured using Near Infrared Spectroscopy (NIRS). Values are an index of phosphocreatine recovery expressed as a rate constant (min-1)
Measured: Measure taken at Baseline and post 12 weeks
Secondary outcomes (3)
Change in Percentage Flow-Mediated Dilation (FMD)
Change in Percentage FMD at 12 weeks. Measured via ultrasound in conjunction with edge detection software. Expressed as %
Measured: Measure taken at Baseline and post 12 weeks
Change in Pulse Wave Velocity (PWV)
Change in PWV at 12 weeks. Measured by Shygmocor Xcel in m/s.
Measured: Measure taken at Baseline and post 12 weeks
Change in Post Occlusive Reactive Hyperemia (PORH)
Change in PORH at 12 weeks. Measured by Laser Speckle Contrast Imager (Moor FLPI-2) in perfusion units (PU). Represents the maximal dilatory response in the microcirculation post 5 minute occlusion.
Measured: Baseline and post 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2020
- Study start14 Oct 2020
- Primary completion1 Jan 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 DiabetesStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Augusta University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ryan Harris, Augusta University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04449198
- Sponsor's protocol ID
- 1595933
- Acronym
- T-St1M
- Status last verified
- Jan 2025
- First submitted
- 11 Jun 2020
- Last updated
- 28 Jan 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Derella CC, Thomas J, Harris RA. Women Have Greater Endothelin-B Receptor Function and Lower Mitochondrial Capacity Compared to Men With Type 1 Diabetes. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2561-2568. doi: 10.1210/clinem/dgad189.
PubMed 37009678
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Type 1 Diabetes, Endothelin, and Skeletal Muscle Mitochondrial Dysfunction: The Role of Sirtuin-1
- ClinicalTrials.gov ID
- NCT04449198
- Acronym / sponsor ID
- T-St1M / 1595933
- Conditions
- Type 1 Diabetes
- Keywords
- diabetes, heart disease, muscle function, blood vessels
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Augusta UniversityUniversity, hospital or other
- Study start
- 14 Oct 2020 (actual)
- Primary completion
- 1 Jan 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 26 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.
The proposed study is designed to test the hypothesis that treatment of resveratrol for 12 weeks will improve both endothelin-B receptor (aim 1) and skeletal muscle mitochondrial function (aim 2) in people with type 1 diabetes.
Detailed description
Preliminary data from the investigators' laboratory demonstrate a negative relationship between hemoglobin A1c (HbA1c) and ETBR function, supporting ETBR may be dysfunctional in the presence of T1D. Using near infrared spectroscopy (NIRS) to non-invasively assess muscle function, the investigators have also observed reduced skeletal muscle mitochondrial function in people with T1D compared to healthy controls. In addition, reduced circulating Sirt1 is associated with both ETBR and skeletal muscle mitochondrial dysfunction in the general population. For the current application, the investigators propose to utilize intradermal microdialysis and NIRS as unique, novel, and minimally invasive methods to investigate ETBR and skeletal muscle mitochondrial function, respectively, in people with T1D. Accordingly, the central hypothesis is that increasing circulating Sirt1 with oral supplementation of resveratrol will improve both ETBR function and mitochondrial skeletal muscle function, reducing overall CVD risk (Figure 1). The investigators will test this hypothesis with the following specific aims:
Aim 1: To test the hypothesis that an increase in Sirt1 will improve ETBR function in people with T1D. The investigators will evaluate ETBR function and circulating Sirt1 at baseline and after a 12-week treatment of resveratrol or placebo. Based on preliminary data, the investigators predict that people with T1D will have ETBR dysfunction compared to controls. In addition, the investigators predict that increasing Sirt1 following resveratrol treatment will improve ETBR function, whereas no change will occur with placebo.
Aim 2: To test the hypothesis that an increase in Sirt1 will improve skeletal muscle mitochondrial function and lower HbA1c in people with T1D. A non-invasive assessment of skeletal muscle function will be performed on people with T1D before and after 12-weeks of treatment with resveratrol or placebo. Compared to controls, the investigators predict that people with T1D will have skeletal muscle dysfunction. Following 12 weeks of resveratrol, the investigators predict that the increase in circulating Sirt1 will improve skeletal muscle function. Additionally, the investigators predict the improved skeletal muscle function will contribute to a subsequent decrease in HbA1c in people with T1D.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Individuals with type 1 diabetes | Experimental | Drug: Resveratrol, Other: PlaceboIndividuals with type 1 diabetes will be randomly assigned to 1 of the 2 interventions (Resveratrol or placebo) |
| Healthy Controls | No intervention | –Healthy individuals who participate will receive no intervention and serve as controls. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Men and premenopausal women
- All races
- Clinical diagnosis of insulin-dependent type 1 diabetes (patients only)
Key exclusion criteria (6 listed)
- Clinical diagnosis of hepatic, cardiovascular, or renal disease
- Uncontrolled diabetes (HbA1C >12%)
- Diabetic complications (i.e. neuropathy)
- Uncontrolled hypertension (>140/90 mm Hg on therapy)
- Pregnancy
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 |
|---|---|---|
| Resveratrol500 mg of oral trans-resveratrol twice daily (in the morning and evening) for 12-weeks | Drug | Individuals with type 1 diabetes |
| Placeboplacebo for 12 weeks | Other | Individuals with type 1 diabetes |
Primary outcome
Change in AUC for ET-1 + BQ-123
Time frame: Measure taken at Baseline and post 12 weeks
Change in Area Under the Curve (AUC) for Cutaneous Vascular Conductance (CVC) in response to co-perfusion of ET-1 + BQ-123 at 12 weeks. Measured using intradermal microdialysis technique in conjunction with Laser Speckle Contrast Imaging (Moor FLPI-2) and beat-by-beat blood pressure monitoring (Finapres NOVA).
Skeletal Muscle Mitochondrial Function
Time frame: Measure taken at Baseline and post 12 weeks
Change in Skeletal Muscle Mitochondrial Function at 12 weeks. Measured using Near Infrared Spectroscopy (NIRS). Values are an index of phosphocreatine recovery expressed as a rate constant (min-1)
3 secondary outcomes
Change in Percentage Flow-Mediated Dilation (FMD)
Time frame: Measure taken at Baseline and post 12 weeks
Change in Pulse Wave Velocity (PWV)
Time frame: Measure taken at Baseline and post 12 weeks
Change in Post Occlusive Reactive Hyperemia (PORH)
Time frame: Baseline and post 12 weeks
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 28 Jan 2025.
- Derived from this study: PubMed 37009678Derella CC, Thomas J, Harris RA. Women Have Greater Endothelin-B Receptor Function and Lower Mitochondrial Capacity Compared to Men With Type 1 Diabetes. J Clin Endocrinol Metab. 2023 Sep 18;108(10):2561-2568. doi: 10.1210/clinem/dgad189.
Related trials for Type 1 Diabetes
Recruiting
Clinical Study to Evaluate the Impact of the Accu-Chek SmartGuide CGM Solution on the Mean Change in Time in Range Compared With Self-Monitoring of Blood Glucose in Participants With Type 1 and Type 2 Diabetes Mellitus
Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus
Active, not recruitingPhase 2
Islet Cell Transplant for Type 1 Diabetes
Type 1 Diabetes Mellitus
Recruiting
T1CARE: A Trial of a Novel Intervention to Address Social Determinants of Health in Young Adults With Type 1 Diabetes
Type 1 Diabetes
Active, not recruitingPhase 4
Diabetes in African Youth
type1diabetes
RecruitingObservational study
Washed Microbiota Transplantation for Type 1 Diabetes Mellitus
Type 1 Diabetes
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Resveratrol in people with Type 1 Diabetes, run by Augusta University 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 3 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: looking for participants now, as of the sponsor's last update on 28 Jan 2025. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Ryan A Harris, PhD, CEP (7067215998, ryharris@augusta.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in AUC for ET-1 + BQ-123 (time frame: Measure taken at Baseline and post 12 weeks). 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?
On the ClinicalTrials.gov record for NCT04449198, which also lists 1 linked publication.
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 28 Jan 2025.