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

NCT05205005 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CARB-005-21S
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Diabetes Mellitus, Type 2

Keywords

Endothelial function; Glycocalyx; Diabetes

Outcome Measures

Primary Outcomes (1)

• Glygocalyx Integrity - Perfused Boundary Region

  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.

  Change from baseline to eight weeks assessment

Secondary Outcomes (3)

• Brachial Artery Flow Mediated Dilation

  Baseline and final assessment (Week 8)

• Insulin-stimulated Leg Blood Flow

  Baseline and final assessment (Week 8)

• Femoral Artery Flow Mediated Dilation

  Baseline and final assessment (Week 8)

Study Arms (2)

Dietary supplementation of glycocalyx precursors (DSGP)

EXPERIMENTAL

Participants will daily ingest 3,712mg (i.e., six capsules) of DSGP for eight weeks. DSGP, commercially available as Endocalyx (Microvascular Health Solutions LLC, Alpine, UT), include glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan.

Drug: Endocalyx

Placebo

PLACEBO COMPARATOR

Participants will daily ingest 6 capsules daily of placebo

Drug: Placebo

Interventions

Endocalyx DRUG

3,712mg (six capsules) of DSGP for eight weeks.

Dietary supplementation of glycocalyx precursors (DSGP)

Placebo DRUG

Ingredients per capsule (6 capsules per day) Nu-Mag Nat 10.00mg Rice Flour White 830 mg Magnesium Stearate 10.00mg

Placebo

Eligibility Criteria

• Age: 45 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age at the time of enrollment
• Diagnosis of T2D by a health care provider, confirmed by chart review
• HbA1c \<9% and fasting blood glucose \<200 mg/dL at screening visit
• Body mass index (BMI) 25-45 kg/m2
• Women should be postmenopausal (absence of menses for at least 1 year)
• Sedentary subjects (\<2 days/week of vigorous exercise)
• Willingness to follow up instructions provided by study team

You may not qualify if:

• Evidence of cardiac arrhythmias, unstable angina (or other cardiac event), heart failure or stroke in the last 12 months
• Evidence of chronic kidney disease stage IV or V (GFR \<30 mL/min)
• Evidence of uncontrolled hypertension, systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \> 110 mmHg on more than 2 occasions in the past 12 months or at screening visit
• Diagnosis of chronic liver disease
• Uncontrolled thyroid dysfunction (abnormal TSH within 3 months of study enrollment)
• Active cancer
• Current use of hormone replacement therapy
• Excessive alcohol consumption (\>14 drinks/week for men, \>7 drinks/week for women)
• Current pregnancy or intent to become pregnant during the course of the study
• Inability to swallow capsules
• Known allergies to any of the compounds in the supplement: glucosamine extract, fucoidan extract, olive extract, artichoke extract, red and white grapes extract, melon concentrate, hyaluronic acid

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Harry S. Truman Memorial, Columbia, MO

Columbia, Missouri, 65201-5275, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Results Point of Contact

• Title: Harry S. Truman Memorial Veterans' Hospital Research Service
• Organization: Harry S. Truman Memorial Veterans' Hospital

Camila.Manrique-Acevedo@va.gov

573- 814-6000

Study Officials

• Camila Margarita M Manrique Acevedo, MD

  Harry S. Truman Memorial, Columbia, MO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Dietary supplement vs placebo

Study Record Dates

• First Submitted: December 20, 2021
• First Posted: January 24, 2022
• Study Start: May 25, 2022
• Primary Completion: March 31, 2024
• Study Completion: July 31, 2024
• Last Updated: May 2, 2025
• Results First Posted: April 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Upon completion of data analysis

Locations

US (1)