Role of Endothelial Dysfunction on Exercise Pressor Reflex in Type 2 Diabetes

Exaggerated blood pressure responses to exercise in individuals with Type 2 Diabetes significantly increase the risk of heart attack, stroke, and cardiovascular death, while also limiting exercise capacity and therapeutic benefits of physical activity. This research will determine whether impaired blood vessel function and excessive cellular damage from oxygen-containing molecules cause these dangerous blood pressure responses during exercise. The findings will establish whether targeting cellular antioxidant systems represents a new therapeutic approach to improve exercise tolerance and reduce cardiovascular risk in t Americans living with diabetes.

Study Overview

• Status: Not yet recruiting
• Conditions: Endothelial Dysfunction; Type 2 Diabetes (T2DM)
• Intervention / Treatment: Dietary supplement: MitoQ (mitoquinol mesylate); Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin
      • Contact: William E Hughes, Ph.D.; Email: whughes@mcw.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Type 2 Diabetes: 18 - 80 years old, able to give informed consent, > 6 months post-diagnosis, > 6 months stable medications for management
• Healthy controls: 18 - 80 years old, able to give informed consent

Exclusion Criteria:

• Type 2 Diabetes: Type 1 diabetes, symptomatic coronary artery disease, cardiovascular event in last year (MI, stroke), uncontrolled or unmanaged hypertension (>160/90 mmHg), heart failure, renal impairments, current or recent (<6 months) tobacco use, hormone replacement therapy, documented neuromuscular disorders, pregnancy
• Healthy Controls: Same as listed in Type 2 Diabetes with Type 2 Diabetes as an exclusion factor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antioxidant Supplementation; MitoQ, a mitochondrial target antioxidant, given once at a dose of 160 mg	Dietary supplement: MitoQ (mitoquinol mesylate); During each testing session, the investigators will be measuring how one treatment of an over-the-counter antioxidant supplement affects blood flow and muscle function. One day participants will orally ingest an over-the-counter antioxidant supplement called MitoQ.
Placebo Comparator: Placebo; A placebo similar visually will be used to compare to MitoQ	Dietary supplement: Placebo; During each testing session, the investigators will be measuring how one treatment of an over-the-counter antioxidant supplement affects blood flow and muscle function. One day participants will orally ingest an over-the-counter antioxidant supplement called MitoQ, while the other they will ingest a placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Arterial Pressure	Change in mean arterial pressure is measured in response to handgrip exercise and post-exercise circulatory occlusion	Prior to and 45 minutes following supplement
Heart Rate	Change in heart rate is measured in response to handgrip exercise and post-exercise circulatory occlusion	Prior to and 45 minutes following supplement

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brachial Artery FMD	Brachial artery FMD a measure of endothelial function will be measured on the non-dominant arm	Prior to and 45 minutes following supplementation
Plasma MitoQ Concentration	Circulating concentrations of MitoQ is assessed in blood via venipuncture	Prior to and 45 minutes following supplementation
Muscle Tissue Oxygenation	We will also place a near-infrared spectroscopy (NIRS) pad on the thenar eminence of the non-paretic hand to non-invasively measure tissue oxygenation via infrared light following the pneumatic forearm cuff inflation/deflation.	Prior to and 45 minutes following supplementation

Collaborators and Investigators

• Sponsor: Medical College of Wisconsin
• Investigators: Principal Investigator: William E Hughes, Ph.D., Medical College of Wisconsin

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): June 30, 2031
• Study Completion (Estimated): December 31, 2031

Study Registration Dates

• First Submitted: November 5, 2025
• First Submitted That Met QC Criteria: November 12, 2025
• First Posted (Estimated): November 14, 2025

Study Record Updates

• Last Update Posted (Estimated): November 14, 2025
• Last Update Submitted That Met QC Criteria: November 12, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; mitoquinone
• Other Study ID Numbers: PRO00053449

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No