Diabetes Mellitus, Type 2Phase 2/3NCT05205005
Targeting the Endothelial Glycocalyx to Enhance Vascular Function and Exercise-Induced Vascular Adaptations in Type 2 Diabetes
A Phase 2/3 study testing Endocalyx in people with Diabetes Mellitus, Type 2, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 45 to 64 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Endocalyx
- 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
- 25 May 2022to 31 Jul 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 45 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 45-74 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Harry S. Truman Memorial, Columbia, MO
Columbia, Missouri, 65201-5275
About this study
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.
Read the detailed description
The prevalence of type 2 diabetes (T2D) continues to increase in the US. Importantly, T2D is widespread among Veterans. This T2D epidemic also contributes to the staggering rates of cardiovascular disease (CVD) and cardiovascular mortality. Current standards of medical care for T2D emphasize prioritizing the use of therapies that decrease CVD risk. Lifestyle modifications, such as increased physical activity, are recommended as first-line therapy for the management of T2D. Unfortunately, the efficacy of these interventions for preventing CVD morbidity and mortality in patients with T2D remains questionable. Evidence indicates that exercise training in T2D subjects does not elicit optimal vascular adaptations, including improvements in endothelial function. It is likely that such lessened vascular adaptations explain why increased physical activity does not lead to a robust reduction in CVD morbidity and mortality in T2D. A better understanding of the mechanisms responsible for the deficit of vascular adaptations to exercise in T2D is required for identifying new adjuvant therapeutics aimed at maximizing the cardiovascular benefits of exercise.
The primary goal of this project is to establish the endothelial glycocalyx as a novel target organ for heightening exercise-induced vascular adaptations. To that end, a dietary supplement that contains glycocalyx precursors (glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) will be used as an innovative "tool" to restore the endothelial glycocalyx in T2D subjects. Demonstration that dietary supplementation of glycocalyx precursors (DSGP) is effective at enhancing endothelial glycocalyx integrity in patients with T2D will be accomplished in the Proof of Concept Clinical Trial Phase (or Aim 1) of this project. Subsequently, in the Expended Clinical Trial Phase (or Aim 2), the use of the DSGP will allow us to test the hypothesis that glycocalyx restoration re-sensitizes the endothelium to shear stress mechanotransduction and thus potentiates exercise-induced vascular adaptations. This project will be the first to determine if targeting the glycocalyx is a viable therapeutic strategy for boosting exercise-induced endothelial benefits in diabetes.
The overarching hypothesis is that endothelial glycocalyx degradation is a key factor that precludes shear stress mechanotransduction and consequent exercise-induced vascular adaptations in T2D. A corollary to this hypothesis is that restoration of the endothelial glycocalyx by DSGP will improve vascular adaptations to exercise in T2D.
Specific aims are as follows:
Aim 1 (Proof of Concept Clinical Trial Phase): Document that DSGP enhances endothelial glycocalyx integrity in Veterans with T2D. The effects of DSGP for eight weeks on glycocalyx integrity and endothelial function will be studied using a double-blinded randomized placebo control trial. Sample size = 24 subjects (12 per group) for Aim 1.
Aim 2 (Expanded Clinical Trial Phase): Demonstrate the permissive role of the endothelial glycocalyx for exercise-induced vascular adaptations in Veterans with T2D. Having shown that endothelial glycocalyx restoration via DSGP in T2D subjects is feasible, will now investigate whether such supplementation potentiates exercise training-induced improvements in endothelial function. This will be accomplished with a factorial balanced design in which T2D subjects will be randomized to DSGP or placebo with and without concurrent exercise training for eight weeks. Sample size = 72 subjects (18 per group).
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Endocalyx, Placebo
- Keywords
- Endothelial function, Glycocalyx, Diabetes
- Medical subject headings
- Diabetes Mellitus, Type 2, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndocalyxDrug
3,712mg (six capsules) of DSGP for eight weeks.
PlaceboDrug
Ingredients per capsule (6 capsules per day) Nu-Mag Nat 10.00mg Rice Flour White 830 mg Magnesium Stearate 10.00mg
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Endocalyx |
| Placebo | Placebo comparator | Participants will daily ingest 6 capsules daily of placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from baseline to eight weeks assessment
Secondary outcomes (3)
Brachial Artery Flow Mediated Dilation
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 is released.
Measured: Baseline and final assessment (Week 8)
Insulin-stimulated Leg Blood Flow
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 achieved by variable IV infusion rates of a 20% dextrose solution. The measurements described will allow for the assessment of the insulin stimulated leg blood flow
Measured: Baseline and final assessment (Week 8)
Femoral Artery Flow Mediated Dilation
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 soon as the pressure in the cuff is released.
Measured: Baseline and final assessment (Week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2022
- Study start25 May 2022
- Primary completion31 Mar 2024
- Study completion31 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- 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
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Dietary supplement vs placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Camila Margarita M Manrique Acevedo, MD, Principal investigator, Harry S. Truman Memorial, Columbia, MO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05205005
- Sponsor's protocol ID
- CARB-005-21S
- Status last verified
- Apr 2025
- First submitted
- 20 Dec 2021
- Last updated
- 2 May 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Details of research products in this project will be in text, table, plots and images that will be disseminated in peer reviewed journals and/or conference proceedings. Datasets that underlie these research products will be made available upon reasonable written request and review with the ACOS/R\&D and the ISSO within a reasonable time
Study at a glance
From the registry record, last updated by the sponsor on 2 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting the Endothelial Glycocalyx to Enhance Vascular Function and Exercise-Induced Vascular Adaptations in Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05205005
- Acronym / sponsor ID
- CARB-005-21S
- Conditions
- Diabetes Mellitus, Type 2
- Keywords
- Endothelial function, Glycocalyx, Diabetes
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 25 May 2022 (actual)
- Primary completion
- 31 Mar 2024 (actual)
- Study completion
- 31 Jul 2024 (actual)
- First posted
- 24 Jan 2022 (actual)
- Results
- Posted 2 Apr 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The prevalence of type 2 diabetes (T2D) continues to increase in the US. Importantly, T2D is widespread among Veterans. This T2D epidemic also contributes to the staggering rates of cardiovascular disease (CVD) and cardiovascular mortality. Current standards of medical care for T2D emphasize prioritizing the use of therapies that decrease CVD risk. Lifestyle modifications, such as increased physical activity, are recommended as first-line therapy for the management of T2D. Unfortunately, the efficacy of these interventions for preventing CVD morbidity and mortality in patients with T2D remains questionable. Evidence indicates that exercise training in T2D subjects does not elicit optimal vascular adaptations, including improvements in endothelial function. It is likely that such lessened vascular adaptations explain why increased physical activity does not lead to a robust reduction in CVD morbidity and mortality in T2D. A better understanding of the mechanisms responsible for the deficit of vascular adaptations to exercise in T2D is required for identifying new adjuvant therapeutics aimed at maximizing the cardiovascular benefits of exercise.
The primary goal of this project is to establish the endothelial glycocalyx as a novel target organ for heightening exercise-induced vascular adaptations. To that end, a dietary supplement that contains glycocalyx precursors (glucosamine sulfate, fucoidan, superoxide dismutase, and high molecular weight hyaluronan) will be used as an innovative "tool" to restore the endothelial glycocalyx in T2D subjects. Demonstration that dietary supplementation of glycocalyx precursors (DSGP) is effective at enhancing endothelial glycocalyx integrity in patients with T2D will be accomplished in the Proof of Concept Clinical Trial Phase (or Aim 1) of this project. Subsequently, in the Expended Clinical Trial Phase (or Aim 2), the use of the DSGP will allow us to test the hypothesis that glycocalyx restoration re-sensitizes the endothelium to shear stress mechanotransduction and thus potentiates exercise-induced vascular adaptations. This project will be the first to determine if targeting the glycocalyx is a viable therapeutic strategy for boosting exercise-induced endothelial benefits in diabetes.
The overarching hypothesis is that endothelial glycocalyx degradation is a key factor that precludes shear stress mechanotransduction and consequent exercise-induced vascular adaptations in T2D. A corollary to this hypothesis is that restoration of the endothelial glycocalyx by DSGP will improve vascular adaptations to exercise in T2D.
Specific aims are as follows:
Aim 1 (Proof of Concept Clinical Trial Phase): Document that DSGP enhances endothelial glycocalyx integrity in Veterans with T2D. The effects of DSGP for eight weeks on glycocalyx integrity and endothelial function will be studied using a double-blinded randomized placebo control trial. Sample size = 24 subjects (12 per group) for Aim 1.
Aim 2 (Expanded Clinical Trial Phase): Demonstrate the permissive role of the endothelial glycocalyx for exercise-induced vascular adaptations in Veterans with T2D. Having shown that endothelial glycocalyx restoration via DSGP in T2D subjects is feasible, will now investigate whether such supplementation potentiates exercise training-induced improvements in endothelial function. This will be accomplished with a factorial balanced design in which T2D subjects will be randomized to DSGP or placebo with and without concurrent exercise training for eight weeks. Sample size = 72 subjects (18 per group).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Dietary supplement vs placebo
| Arm | Type | Receives |
|---|---|---|
| Dietary supplementation of glycocalyx precursors (DSGP) | Experimental | Drug: EndocalyxParticipants 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. |
| Placebo | Placebo comparator | Drug: PlaceboParticipants will daily ingest 6 capsules daily of placebo |
Who may qualify
- Ages
- 45 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 45-74 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)
Key exclusion criteria (11 listed)
- 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)
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 |
|---|---|---|
| Endocalyx3,712mg (six capsules) of DSGP for eight weeks. | Drug | Dietary supplementation of glycocalyx precursors (DSGP) |
| PlaceboIngredients per capsule (6 capsules per day) Nu-Mag Nat 10.00mg Rice Flour White 830 mg Magnesium Stearate 10.00mg | Drug | Placebo |
Primary outcome
Glygocalyx Integrity - Perfused Boundary Region
Time frame: 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.
3 secondary outcomes
Brachial Artery Flow Mediated Dilation
Time frame: Baseline and final assessment (Week 8)
Insulin-stimulated Leg Blood Flow
Time frame: Baseline and final assessment (Week 8)
Femoral Artery Flow Mediated Dilation
Time frame: Baseline and final assessment (Week 8)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 May 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Details of research products in this project will be in text, table, plots and images that will be disseminated in peer reviewed journals and/or conference proceedings. Datasets that underlie these research products will be made available upon reasonable written request and review with the ACOS/R\&D and the ISSO within a reasonable time
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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. This study is not recruiting at the moment.
Camila Margarita M Manrique Acevedo, MD principal investigator
Harry S. Truman Memorial, Columbia, MO
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Endocalyx in people with Diabetes Mellitus, Type 2, run by VA Office of Research and Development 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 7 inclusion and 11 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: finished, as of the sponsor's last update on 2 May 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 2 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glygocalyx Integrity - Perfused Boundary Region (time frame: Change from baseline to eight weeks assessment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 2 May 2025.