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NCT05205005

Targeting the Endothelial Glycocalyx to Enhance Vascular Function and Exercise-Induced Vascular Adaptations in Type 2 Diabetes

Completed Phase 2, PHASE3 Results posted Last updated 2 May 2025
What this trial tests

Phase 2, PHASE3 trial testing Endocalyx in Diabetes Mellitus, Type 2 in 24 participants. Completed in 31 July 2024.

Timeline
25 May 2022
Primary endpoint
31 March 2024
31 July 2024

Quick facts

Lead sponsorVA Office of Research and Development
PhasePhase 2, PHASE3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment24
Start date25 May 2022
Primary completion31 March 2024
Estimated completion31 July 2024
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 45 to 64, any sex, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Glygocalyx Integrity - Perfused Boundary Region Primary · Change from baseline to eight weeks assessment

Glycocalyx integrity will be assessed non-invasively using the GlycoCheck. The Glycocheck video microscope instrument will be placed under the subject's tongue to assess red blood cell penetration of the glycocalyx lining. PBR (perfused boundary region) is a measure of distance (mcm) that red blood cells penetrate into the glycocalyx. An increase in PBR in indicative of lower glycocalyx integrity.

GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)0.11± 0.17
Placebo-0.16± 0.15
Brachial Artery Flow Mediated Dilation Secondary · Baseline and final assessment (Week 8)

Arterial measurements will be performed by imaging the brachial artery artery longitudinally using high-resolution duplex ultrasonography. Arterial vasodilatory responses to hyperemia (flow-mediated dilation; FMD) will be examined by inflating a cuff up to 250 mmHg for five minutes. Before, during and after rapid release of the cuff, brachial artery blood flow velocity and diameter will be continuously measured. This is a measurement of endothelial function. When assessing FMD, the cuff will squeeze the arm tightly; however, any discomfort will be alleviated as soon as the pressure in the cuff

Baseline
GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)2.93± 0.39
Placebo2.14± 0.27
Final
GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)3.20± 0.47
Placebo1.87± 0.34
Insulin-stimulated Leg Blood Flow Secondary · Baseline and final assessment (Week 8)

Insulin-stimulated leg blood flow will be assessed via Doppler and contrast-enhanced ultrasound during an insulin-dextrose clamp. After a minimum of 20 minutes in supine rest, baseline cardiovascular measurements will be collected, including Doppler and contrast-enhanced ultrasound-based measures, blood samples obtained and then the insulin clamp will start. Briefly, insulin (Humulin R U-100) will be infused via IV at a constant rate of 80mU/m2 body surface area/min for the three-hour period. Blood glucose will be measured at five-minute intervals and maintained at fasting levels; this will be

Baseline
GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)5.98± 11.92
Placebo16.93± 15.38
Final
GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)2.97± 12.14
Placebo9.55± 9.03
Femoral Artery Flow Mediated Dilation Secondary · Baseline and final assessment (Week 8)

Arterial measurements will be performed by imaging the femoral artery longitudinally using high-resolution duplex ultrasonography. Arterial vasodilatory responses to hyperemia (flow-mediated dilation; FMD) will be examined by inflating a cuff up to 250 mmHg for five minutes. Before, during and after rapid release of the cuff, femoral artery blood flow velocity and diameter will be continuously measured (these are used to calculate the FMD). This is a measurement of endothelial function. When assessing FMD, the cuff will squeeze the leg tightly; however, any discomfort will be alleviated as soo

Baseline
GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)2.93± 0.39
Placebo2.14± 0.27
Final
GroupValue95% CI
Dietary Supplementation of Glycocalyx Precursors (DSGP)3.20± 0.47
Placebo1.87± 0.34

Adverse events — posted to ClinicalTrials.gov

Time frame: Screening visit until final assessment (week 8 assessment). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dietary Supplementation of Glycocalyx Precursors (DSGP)
Serious: 0/12 (0%)
Deaths: 0/12
Placebo
Serious: 0/12 (0%)
Deaths: 0/12
Other adverse events (7 terms — click to expand)

ReactionSystemDietary Supplementation of…Placebo
Tendon injuryMusculoskeletal and connective tissue disorders
Loose stoolsGastrointestinal disorders
Stomach AcheGastrointestinal disorders
HeadacheNervous system disorders
PT/PTT lab elevationBlood and lymphatic system disorders
ItchinessSkin and subcutaneous tissue disorders
HemorrhoidsGastrointestinal disorders

Data from ClinicalTrials.gov NCT05205005 adverse events section.

Sponsor's own description

The prevalence of type 2 diabetes (T2D) continues to increase in the US, with 26.8 million adults carrying a diagnosis. Importantly, T2D is widespread in the Veteran population. This epidemic of T2D also contributes to the staggering rates of cardiovascular disease and cardiovascular mortality. Lifestyle modifications, including increased physical activity, are recommended as first-line therapy for the management of T2D. Unfortunately, patients with T2D exhibit diminished vascular adaptations to exercise. The proposed project will test the overall hypothesis that degradation of the endothelial glycocalyx, a characteristic feature of T2D, precludes shear stress mechanotransduction and consequent exercise-induced vascular adaptations. As such, the investigators pose that restoration of the endothelial glycocalyx via dietary supplementation of glycocalyx precursors will potentiate vascular adaptations to exercise in Veterans with T2D.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Impact of dietary supplementation of glycocalyx precursors on vascular function in type 2 diabetes.
    Smith JA, Ramirez-Perez FI, Burr K, Gonzalez-Vallejo JD, et al · · 2024 · cited 7× · PMID 39480270 · DOI 10.1152/japplphysiol.00651.2024

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Other recruiting trials for Diabetes Mellitus, Type 2

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing