Type 1 Diabetes, Endothelin, and Skeletal Muscle Mitochondrial Dysfunction: The Role of Sirtuin-1

NCT ID: NCT04449198

Last Updated: 2025-01-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-14
• Study Completion Date: 2027-07-01

Brief 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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Individuals with type 1 diabetes

Individuals with type 1 diabetes will be randomly assigned to 1 of the 2 interventions (Resveratrol or placebo)

Group Type: EXPERIMENTAL

Resveratrol

Intervention Type: DRUG

500 mg of oral trans-resveratrol twice daily (in the morning and evening) for 12-weeks

Placebo

Intervention Type: OTHER

placebo for 12 weeks

Healthy Controls

Healthy individuals who participate will receive no intervention and serve as controls.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Resveratrol

500 mg of oral trans-resveratrol twice daily (in the morning and evening) for 12-weeks

Intervention Type: DRUG

Placebo

placebo for 12 weeks

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Men and premenopausal women
• All races
• Clinical diagnosis of insulin-dependent type 1 diabetes (patients only)

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Augusta University

OTHER

Sponsor Role: lead

Responsible Party

Ryan Harris

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Augusta University/Georgia Prevention Institute/ Laboratory of Integrative and Exercise Physiology

Augusta, Georgia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ryan A Harris, PhD, CEP

Role: CONTACT

ryharris@augusta.edu

7067215998

Jacob Looney, MS

Role: CONTACT

jlooney@augusta.edu

7067215483

Facility Contacts

Ryan Harris, PhD, CEP

Role: primary

ryharris@augusta.edu

706-721-5998

Casey Derella, BS

Role: backup

cderella@augusta.edu

706-721-5483

References

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.

Reference Type: DERIVED

PMID: 37009678 (View on PubMed)

Other Identifiers

1595933

Identifier Type: -

Identifier Source: org_study_id