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Active, not recruiting

NCT Number: NCT05966415

Endocalyx for Heart Failure

The goal of this randomized, double-blind, placebo-controlled study is to assess whether the food supplement Endocalyx Pro reduces sodium and water excess in patients with chronic heart failure.

The main questions it aims to answer are:

1. To assess whether the food supplement Endocalyx reduces sodium and water excess in patients with chronic heart failure. 2. To determine the contribution of different potential working mechanisms of Endocalyx in heart failure patients. 3. To evaluate whether the food supplement Endocalyx will improve patient-reported outcomes such as fluid overload symptoms and quality of life. 4. To confirm the previously demonstrated safety of Endocalyx in subjects with chronic heart failure.

Participants will be randomized to Endocalyx Pro or Placebo daily for 8 weeks, and will be followed 12 weeks.

Active, not recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Chronic Heart Failure

Age range

18 year–110 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Amsterdam UMC

Amsterdam, North Holland, 1105 AZ, Netherlands

About this study

Primary Objective:

  • To assess whether the food supplement Endocalyx Pro™ (further termed Endocalyx) reduces sodium and water excess in patients with chronic heart failure.

Secondary Objectives:

  • To evaluate whether Endocalyx will improve physical limitations and patient-reported outcomes such as fluid overload symptoms and quality of life.
  • To determine the working mechanisms of Endocalyx in heart failure patients.
  • To determine whether Endocalyx will alter tissue sodium content.
  • To analyze whether Endocalyx reduces total body water and body weight.
  • To assess whether Endocalyx affects office blood pressure, 24-hour blood pressure, peripheral resistance and cardiac output.
  • To assess whether Endocalyx improves microcirculation characteristics.
  • To evaluate whether Endocalyx reduces systemic inflammation and monocyte activation.
  • To confirm safety of Endocalyx in the heart failure population a. To compare the incidence of (serious) adverse events between Endocalyx and placebo.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Documented or suspected heart failure with reduced ejection fraction (HFrEF and HFmrEF according to ESC guidelines).
  • Signs of congestion, defined as:

a. Elevated NT-proBNP levels: i. >450 pg/ml in subjects aged <55 years. ii. >900 pg/ml in subjects aged 55-75 years. iii. >1800 pg/ml in subjects aged >75 years. AND b. Use of diuretics, OR c. Presence of peripheral edema, OR d. Complaints of orthopnea or paroxysmal nocturnal dyspnea, OR e. A chest X-rays with sings of volume overload, OR f. Hypertension, as defined by an office blood pressure >140/90 mmHg.

  • Stable diuretic and antihypertensive treatment for the previous 3 weeks.
  • Subject, or legal representative, has voluntarily signed and dated an Informed Consent Form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions. The informed consent must be signed before any study-specific procedures are performed.

Rationale for the inclusion criteria:

(1-3) To select the adequate subject population with appropriate disease severity for the evaluation. NT-proBNP levels are known to increase with age.(21, 22) The cutoffs of NT-proBNP levels were selected according the 2021 European Society of Cardiology Guidelines for the diagnosis and treatment of acute and chronic heart failure. (23) (4) In accordance with GCP.

Should inclusion prove difficult, we will lower required NT-proBNP levels by 25% to respectively 338, 675 and 1350 pg/ml. We will notify the METC of this decision.

Exclusion criteria

  • Age <18 years.
  • Estimated glomerular filtration rate (eGFR) <15 ml/min/1.73m2 measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
  • Severe symptoms of (orthostatic) hypotension.
  • An acute coronary syndrome, stroke, transient ischemic attack or cardiovascular surgery in the last 3 months.
  • Hospitalization for heart failure in the past 3 weeks.
  • Dialysis treatment or expected initiation of dialysis within 3 months of screening.
  • Women of child bearing potential.
  • Planned surgery in the next 8 weeks.
  • Major surgery in the previous 4 weeks.
  • Use of any other investigational drug.
  • Presence of significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy of less than 1 year.
  • A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
  • Known hypersensitivity to seaweed, corn, artichoke, grape, melon or to any of the excipients of Endocalyx.
  • Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.

Treatment and study plan

Endocalyx Pro

Dietary Supplement

4 capsules once daily OR 2 capsules twice daily.

Other names: Endocalyx

Placebo

Other

4 capsules once daily OR 2 capsules twice daily

Primary outcomes

  1. Change in NT-proBNP in patients with chronic heart failure with (mildly) reduced ejection fraction.

    Time frame: 8 weeks

    Our primary outcome will be the degree of volume overload as measured by the change in NT-proBNP from baseline to the study end at 8 weeks. The primary analysis will be performed using a mixed model for repeated measures (MMRM) on log-transformed NT-proBNP values. We will first fit models to analyze the overall treatment effect, and thereafter fit different models to assess the treatment effect over time (visit-specific).

    Our primary analysis will be an intention-to-treat analysis. To check the robustness of our results, we will perform a per protocol analysis. Subjects that withdraw their consent and stop the study medication will be asked to consent for a NT-proBNP measurement at the scheduled end of the study.

    NT-proBNP will be measured at screening visit, week 0 (randomization), week 4 and 8

Secondary outcomes

  1. Change in 24 hour blood pressure, daytime blood pressure, nighttime blood pressure in Endocalyx treated patients when compared with subject receiving Placebo

    Time frame: 8 weeks

    24-hour ambulatory blood pressure (systolic blood pressure, diastolic blood pressure and mean arterial blood pressure) will be measured at screening, week 4 and week 8

  2. Change in total body water in Endocalyx treated patients when compared with subject receiving Placebo

    Time frame: 8 weeks

    Total body water and body weight will be measured with a body composition monitor at week 0 (randomization visit), 4 and 8

  3. Change in body weight (in kilograms) in Endocalyx treated patients when compared with subject receiving Placebo

    Time frame: 8 weeks

    Body weight will be measured at week 0 (randomization visit), 4 and 8

  4. Change in hemodynamic parameters in Endocalyx treated patients when compared with subject receiving Placebo

    Time frame: 8 weeks

    Nexfin will be used to measure hemodynamic parameters (such as heart rate, cardiac output and total peripheral resistance) at week 0 (randomization visit), 4 and 8

  5. Concentration change of Adrenomedullin in Endocalyx treated patients when compared with subject receiving Placebo

    Time frame: 0-8 weeks

    Adrenomedullin concentrations willl be measured in plasma. Blood will be collected at visits 0,1,2 and 3 (week 0-8)

  6. Change/difference in ratio of classical, non-classical and intermediate monocyte subsets.

    Time frame: 0-8 weeks

    will be isolated from peripheral blood mononuclear cells (PBMCs) collected at week 0 and 8

  7. Difference in chemokine. scavenger receptors, and surface proteins associated with monocyte adhesion, migration and activation concentrations, in Endocalyx treated patients when compared with subject receiving Placebo

    Time frame: 8 weeks

    will be isolated from peripheral blood mononuclear cells (PBMCs) collected at week 0 and 8

  8. Lipopolysaccharide-mediated cytokine secretion of monocytes in vitro in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 8 weeks

    will be isolated from peripheral blood mononuclear cells (PBMCs) collected at week 0 and 8

  9. Difference in hospitalization rates due to heart failure in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 12 weeks

    (serious) adverse events will be asked regularly throughout the study (during each study visit, and telephone call)

  10. Distance covered during the 6 minute walking tests in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 8 weeks

    Difference and change in meters covered during the six minute walking tests will be assessed during visit 0 (week 0) and 3 (week 8)

  11. Change in self-reported Quality of life in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 8 weeks

    Quality of life assessment with the RAND-36 and the Dutch version of the Minnesota Living with Heart Failure Questionnaire (MLHFQ). The MLHFQ is one of the most widely used instruments for evaluating health-related quality of life in heart failure patients internationally and has been recommended by a systematic and reliable expert-based evaluation of available heart failure-specific health-related quality of life questionnaires.

    Questionnaires will be filled in at week 0,4an 8

  12. Difference in incidence of (serious) adverse events in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 12 weeks

    (serious) adverse events will be asked regularly throughout the study (during each study visit, and telephone call)

  13. Pharmacokinetics of Endocalyx

    Time frame: 0-8 weeks

    (precursors of) glycosaminoglycans will be measured in urine and blood at set timepoints in a subset of patients who give additional informed consent at week 0,4 and 8

  14. Skin sodium content in skin biopsies

    Time frame: 0-8 weeks

    In a subset of patients who give additional informed consent for skin biopsies, skin sodium content will be measured.

    Changes and differences in Endocalyx treated patients will be compared with subjects receiving Placebo.

    Skin biopsies will be taken at week 0 and 8.

  15. monocyte and macrophage expression and density in skin biopsies

    Time frame: 0-8 weeks

    In a subset of patients who give additional informed consent for skin biopsies the migration of monocytes, skin macrophage density and expression will be assessed.

    Changes and differences in Endocalyx treated patients will be compared with subjects receiving Placebo.

    Skin biopsies will be taken at week 0 and 8.

  16. Change/difference in blood pressure in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 12 weeks

    Office blood pressure (systolic and diastolic blood pressure) will be measured (standardized) during each study visit.

  17. Difference/Change in 24-hour urine sodium and potassium excretion in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 8 weeks

    Subjects will collect 24-hour urine for the visits 1 and 3 (week 0 and 8 respectively)

  18. Plasma aldosterone and renin change/difference in Endocalyx treated patients when compared with subjects receiving Placebo

    Time frame: 8 weeks

    Blood will be collected at visits 0,1,2 and 3 (week 0-8)

  19. Differential treatment effects of Endocalyx in male and female patients

    Time frame: 12 weeks

    Exploratory subgroup analyses are planned to evaluate differential treatment effects of Endocalyx in male and female patients. Previous studies have demonstrated that women have lower skin sodium content than men and show less of an increase in skin sodium content after a high sodium diet.(36, 37) Also, heart failure is different in men and women. Women are more likely to have a non-ischemic ideology and hypertension as a cause of heart failure, and respond differently to treatment.(38) Considering these important gender differences in both heart failure characteristics and the suggested working mechanism of Endocalyx, it is likely that Endocalyx will have different effects in men and women.

  20. Percent change in antihypertensive drug dosage or number prescribed

    Time frame: 8 weeks

    % change in antihypertensive drug dosage or number prescribed in Endocalyx treated patients when compared with subjects receiving Placebo. Medication will be reviewed during visits 0-3 and during the telephone calls

  21. Percent change in diuretics (dosage or number prescribed)

    Time frame: 8 weeks

    % change in diuretics (dosage or number prescribed) prescribed in Endocalyx treated patients when compared with subjects receiving Placebo. Medication will be reviewed during visits 0-3 and during the telephone calls

  22. Change from baseline in total vessel density and perfused vessel density

    Time frame: 8 weeks

    The total vessel density and perfused vessel density will be measured using Sidestream Dark Field imaging

  23. Change from baseline in VEGF-C

    Time frame: 8 weeks

    Vascular endothelial growth factor C (VEGF-C) levels (in pg/mL) will be determined with ELISA

  24. Change from baseline in proportion of perfused vessels

    Time frame: 8 weeks

    The proportion of perfussed vessels will be measured using Sidestream Dark Field imaging.

  25. Change from baseline in microvascular flow index

    Time frame: 8 weeks

    The microvascular flow index will be measured using Sidestream Dark Field imaging.

  26. Change from baseline in microvascular health score

    Time frame: 8 weeks

    The microvascular health score will be measured using Sidestream Dark Field imaging.

  27. Change from baseline in transepidermal water loss

    Time frame: 8 weeks

    Transepidermal water loss will be measured with the Tewameter® TM Hex probe

  28. Change from baseline in skin hydration

    Time frame: 8 weeks

    The skin hydration will be measured using the Corneometer® CM 825 probeTime

  29. Change from baseline in VEGF-A

    Time frame: 8 weeks

    Vascular endothelial growth factor A (VEGF-A) levels (in pg/mL) will be determined with ELISA

  30. Change from baseline in Angiopoietin 1

    Time frame: 8 weeks

    Angiopoietin 1 levels (in pg/mL) will be determined with ELISA

  31. Change from baseline in Angiopoietin 2

    Time frame: 8 weeks

    Angiopoietin 2 levels (in pg/mL) will be determined with ELISA

  32. Change from baseline in TIE2

    Time frame: 8 weeks

    TIE 2 levels (in pg/mL) will be determined with ELISA

Sponsors and collaborators

Lead sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Other

Registry information

Official study title

Glycocalyx Restoration in Chronic Heart Failure: a Proof of Concept, Randomized, Double-blind, Placebo-controlled Study

Acronym: GLYCO-HF

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Jul 28, 2023
Registry last updated
Aug 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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