Endocalyx in Treatment Resistent Hypertension (GLYCO-TRH)

Glycocalyx Restoration in Treatment Resistant Hypertension: a Proof of Concept, Randomized, Double-blind, Placebo-controlled Study

The goal of this randomized, double-blind, placebo-controlled study is to assess whether the food supplement Endocalyx lowers blood pressure in patients with treatment resistant hypertension.

Study Overview

• Status: Recruiting
• Conditions: Treatment Resistant Hypertension
• Intervention / Treatment: Dietary supplement: Endocalyx Pro; Other: Placebo

Detailed Description

During this intervention study, subjects will receive either a placebo or Endocalyx for 12 weeks. The main objective of this study is to assess whether the food supplement Endocalyx lowers blood pressure in patients with treatment resistant hypertension.

Secondary objectives are:

• Change from baseline in office blood pressure and 24-hour blood pressure profiles in subjects with treatment resistant hypertension.
• To assess whether sodium intake, sex or kidney function modulates the effect of Endocalyx on blood pressure.
• Change from baseline in total vessel density, perfused vessel density, proportion of perfused vessels and microvascular health score
• To assess the effect of Endocalyx on total peripheral resistance.
• The effect of Endocalyx on quality of life.
• To estimate the potential impact of Endocalyx on long-term cardiovascular protection and health care costs.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Rik Olde Engberink, MD PhD; Phone Number: 0031205661930; Email: r.h.oldeengberink@amsterdamumc.nl
• Study Contact Backup: Name: Sanédy Simon, MD; Phone Number: 0031205667789; Email: s.s.a.simon@amsterdamumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1105 AZ
      • Recruiting
      • Amsterdam UMC
      • Contact: Rik Olde Engberink, MD PhD; Phone Number: +31(0)205661930; Email: r.h.oldeengberink@amsterdamumc.nl
      • Contact: Sanédy Simon, MD; Phone Number: +31(0)20567789; Email: s.s.a.simon@amsterdamumc.nl
      • Contact: C.L. Zwager, MD
      • Contact: S.S.A Simon, MD
      • Contact: R.H.G Olde Engberink, Nephrologist

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Treatment resistant hypertension defined as

   1. an uncontrolled office BP (≥140/90 mmHg).
   2. is on a regimen of ≥3 adequately dosed antihypertensive agents of different classes, including a diuretic, at maximum tolerated dose based on investigator judgment.
2. Stable diuretic and antihypertensive treatment for the previous 3 weeks.
3. Subject, or legal representative, has voluntarily signed and dated an Informed Consent Form, approved by the Independent Ethics Committee (IEC).

Exclusion Criteria:

1. Age <18 years.
2. Estimated glomerular filtration rate (eGFR) <20 ml/min/1.73m2 measured by the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine formula and the 2012 cystatin C CKD-EPI formula.
3. A mean seated systolic blood pressure of at least 180 mmHg or a diastolic blood pressure of at least 110 mmHg.
4. Known secondary hypertension
5. An acute coronary syndrome, stroke, transient ischemic attack or cardiovascular surgery in the last 3 months.
6. Hospitalization for heart failure in the past 3 weeks.
7. Dialysis treatment or expected initiation of dialysis within 3 months of screening.
8. Women of child bearing potential who are not taking adequate contraception (i.e. <1% failure rate).
9. Planned surgery in the next 12 weeks
10. Major surgery in the previous 4 weeks.
11. Use of prednisolone >5 mg/day
12. Use of any other investigational drug.
13. Presence of significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy of less than 1 year.
14. A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
15. Known hypersensitivity to seaweed, corn, artichoke, grape, melon or to any of the excipients of Endocalyx.
16. Known hypersensitivity or allergies for milk, eggs, fish, crustacean shellfish, tree nuts, peanuts, wheat and soybeans.
17. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Endocalyx Pro; Endocalyx is a food supplement that is distributed by Microvascular Health Solutions LLC in Chattanooga, Tennessee. Patients will receive 4 capsules Endocalyx per day, for 12 consecutive weeks. The capsules are orally administered and can be taken with water, on an empty stomach or with food. If possible, the patient will take 2 capsules in the morning, and 2 capsules in the afternoon. If preferred by the patient, the 4 capsules could also be taken once daily in the morning.	Dietary supplement: Endocalyx Pro; 4 capsules once daily OR 2 capsules twice daily
Placebo Comparator: Placebo; Placebo pills will be provided by Microvascular Health Solutions and are matched with the Endocalyx capsules. The placebo capsules contain no active pharmaceutical ingredients and contain solely widely used excipients. Patients will receive 4 capsules of the placebo per day for 12 consecutive weeks. The capsules are orally administered and can be taken with water, on an empty stomach or with food. If possible, the patient will take 2 capsules in the morning, and 2 capsules in the afternoon. If preferred by the patient, the 4 capsules could also be taken once daily in the morning.	Other: Placebo; 4 capsules once daily OR 2 capsules twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in 24-hour systolic blood pressure	We will perform an uncorrected analysis and an analysis that is corrected for the reported and measured changes in antihypertensive medication use.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in 24-hour diastolic blood pressure		12 weeks
Change from baseline in seated systolic office blood pressure		12 weeks
Change from baseline in seated diastolic office blood pressure		12 weeks
Change from baseline in percentage of patients with a night-time blood pressure dip	The nighttime blood pressure dipping status will be measured with a 24-hour blood pressure measurements. Patients will be classified as a 'dippers' when the nighttime systolic blood pressure and/or diastolic blood pressure falls >10% and <20% compared to daytime readings. Exteme dippers are described as those with blood pressure fall of at least 20%. Patients with blood pressure fall between 0 and 10% are classified as non-dippers.	12 weeks
Percentage of patients achieving a seated office blood pressure <140/90 mmHg after intervention	Participants achieved a response if the systolic blood pressure is below 140 mmHg and the diastolic blood pressure is below 90 mmHg	12 weeks
Percentage of patients that needed additional antihypertensive drugs and/or higher dosage of antihypertensive drugs during the study		12 weeks
Percentage of patients that required lowering of their antihypertensive drugs during the study		12 weeks
Change from baseline in total vessel density and perfused vessel density	The total vessel density and perfused vessel density will be measured using Sidestream Dark Field imaging.	12 weeks
Change from baseline in proportion of perfused vessels	The proportion of perfussed vessels will be measured using Sidestream Dark Field imaging.	12 weeks
Change from baseline in microvascular flow index	The microvascular flow index will be measured using Sidestream Dark Field imaging.	12 weeks
Change from baseline in microvascular health score	The microvascular health score will be measured using Sidestream Dark Field imaging.	12 weeks
Change from baseline in heart rate	The heart rate will be measured using the Nexfin device	12 weeks
Change from baseline in total peripheral resistance	The total pheripheral resistance will be measured using the Nexfin device	12 weeks
Change from baseline in cardiac output	The cardiac output will be measured using the Nexfin device	12 weeks
Change from baseline in quality of life	Quality of life will be evaluated by the SF-36 questionnaire.	12 weeks
The potential impact of Endocalyx on long-term cardiovascular protection and health care costs.	The EQ-5D-5L questionnaire will be used to score a patient health status and will be transposed in quality adjusted life years (QALY's).	12 weeks
Change from baseline in skin sodium content	Skin sodium content will measured using a 7T sodium MRI	12 weeks
Change from baseline in muscle sodium content	Muscle sodium content will measured using a 7T sodium MRI	12 weeks
Change from baseline in skin water content	Skin water content will measured using a 7T H-MRI	12 weeks
Change from baseline in muscle water content	Muscle water content will measured using a 7T H-MRI	12 weeks
Change from baseline in transepidermal water loss	Transepidermal water loss will be measured with the Tewameter® TM Hex probe	12 weeks
Change from baseline in skin hydration	The skin hydration will be measured using the Corneometer® CM 825 probe	12 weeks
Change from baseline in total body water	The change in total body water (liter) will be measured using the bioelectrical impendance analysis	12 weeks
Incidence of adverse events in the Endocalyx group compared to the placebo group		12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess whether sodium intake, measured using 24-hour urine collection, modulate the effect of Endocalyx on blood pressure.	We will study the (possible) modulatory effect sodium intake (mmol/L), measuring using 24 hours urine collection, on the effect of endocalyx on blood pressure.	12 weeks
To assess whether sex modulate the effect of Endocalyx on blood pressure.	The association between sex and the effect of endocalyx on blood pressure.	12 weeks
To assess whether kidney function modulate the effect of Endocalyx on blood pressure.	The association between kidney function and the effect of endocalyx on blood pressure.	12 weeks

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Collaborators: Dutch Heart Foundation; Dutch Kidney Foundation; Microvascular Health Solutions LLC

Study record dates

Study Major Dates

• Study Start (Actual): January 21, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: January 20, 2025
• First Submitted That Met QC Criteria: April 15, 2025
• First Posted (Actual): April 23, 2025

Study Record Updates

• Last Update Posted (Actual): April 23, 2025
• Last Update Submitted That Met QC Criteria: April 15, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: hypertension; Glycocalyx; Glycosaminoglycans; non-osmotic sodium storage
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Hypertension
• Other Study ID Numbers: NL85685.018.24

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared with other researcher

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No