A Phase 2 interventional study of Endocalyx Pro and placebo in Chronic Heart Failure, sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA). Active, not recruiting at 1 site in Netherlands. Open to participants aged 18 Years to 110 Years. Per ClinicalTrials.gov, last updated 2026-08-24.
Sponsored by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) · Phase 2, Interventional, and Treatment
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:
Participants will be randomized to Endocalyx Pro or Placebo daily for 8 weeks, and will be followed 12 weeks.
Primary Objective:
1. 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 determine the working mechanisms of Endocalyx in heart failure patients.
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) is the lead sponsor of 512 studies on the registry; 178 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
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:
Endocalyx is a food supplement that is distributed by Microvascular Health Solutions LLC in Alpine, Utah. Patients will receive 4 capsules Endocalyx per day, for 8 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
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 8 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.
Also known as: Endocalyx
4 capsules once daily OR 2 capsules twice daily
Change in NT-proBNP in patients with chronic heart failure with (mildly) reduced ejection fraction.
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
Time frame: 8 weeks
Change in 24 hour blood pressure, daytime blood pressure, nighttime blood pressure in Endocalyx treated patients when compared with subject receiving Placebo
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
Time frame: 8 weeks
Change in total body water in Endocalyx treated patients when compared with subject receiving Placebo
Total body water and body weight will be measured with a body composition monitor at week 0 (randomization visit), 4 and 8
Time frame: 8 weeks
Change in body weight (in kilograms) in Endocalyx treated patients when compared with subject receiving Placebo
Body weight will be measured at week 0 (randomization visit), 4 and 8
Time frame: 8 weeks
Change in hemodynamic parameters in Endocalyx treated patients when compared with subject receiving Placebo
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
Time frame: 8 weeks
Concentration change of Adrenomedullin in Endocalyx treated patients when compared with subject receiving Placebo
Adrenomedullin concentrations willl be measured in plasma. Blood will be collected at visits 0,1,2 and 3 (week 0-8)
Time frame: 0-8 weeks
Change/difference in ratio of classical, non-classical and intermediate monocyte subsets.
will be isolated from peripheral blood mononuclear cells (PBMCs) collected at week 0 and 8
Time frame: 0-8 weeks
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
will be isolated from peripheral blood mononuclear cells (PBMCs) collected at week 0 and 8
Time frame: 8 weeks
Lipopolysaccharide-mediated cytokine secretion of monocytes in vitro in Endocalyx treated patients when compared with subjects receiving Placebo
will be isolated from peripheral blood mononuclear cells (PBMCs) collected at week 0 and 8
Time frame: 8 weeks
Difference in hospitalization rates due to heart failure in Endocalyx treated patients when compared with subjects receiving Placebo
(serious) adverse events will be asked regularly throughout the study (during each study visit, and telephone call)
Time frame: 12 weeks
Distance covered during the 6 minute walking tests in Endocalyx treated patients when compared with subjects receiving Placebo
Difference and change in meters covered during the six minute walking tests will be assessed during visit 0 (week 0) and 3 (week 8)
Time frame: 8 weeks
Change in self-reported Quality of life in Endocalyx treated patients when compared with subjects receiving Placebo
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
Time frame: 8 weeks
Difference in incidence of (serious) adverse events in Endocalyx treated patients when compared with subjects receiving Placebo
(serious) adverse events will be asked regularly throughout the study (during each study visit, and telephone call)
Time frame: 12 weeks
Pharmacokinetics of Endocalyx
(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
Time frame: 0-8 weeks
Skin sodium content in skin biopsies
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.
Time frame: 0-8 weeks
monocyte and macrophage expression and density in skin biopsies
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.
Time frame: 0-8 weeks
Change/difference in blood pressure in Endocalyx treated patients when compared with subjects receiving Placebo
Office blood pressure (systolic and diastolic blood pressure) will be measured (standardized) during each study visit.
Time frame: 12 weeks
Difference/Change in 24-hour urine sodium and potassium excretion in Endocalyx treated patients when compared with subjects receiving Placebo
Subjects will collect 24-hour urine for the visits 1 and 3 (week 0 and 8 respectively)
Time frame: 8 weeks
Plasma aldosterone and renin change/difference in Endocalyx treated patients when compared with subjects receiving Placebo
Blood will be collected at visits 0,1,2 and 3 (week 0-8)
Time frame: 8 weeks
Differential treatment effects of Endocalyx in male and female patients
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.
Time frame: 12 weeks
Percent change in antihypertensive drug dosage or number prescribed
% 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
Time frame: 8 weeks
Percent change in diuretics (dosage or number prescribed)
% 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
Time frame: 8 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
Time frame: 8 weeks
Change from baseline in VEGF-C
Vascular endothelial growth factor C (VEGF-C) levels (in pg/mL) will be determined with ELISA
Time frame: 8 weeks
Change from baseline in proportion of perfused vessels
The proportion of perfussed vessels will be measured using Sidestream Dark Field imaging.
Time frame: 8 weeks
Change from baseline in microvascular flow index
The microvascular flow index will be measured using Sidestream Dark Field imaging.
Time frame: 8 weeks
Change from baseline in microvascular health score
The microvascular health score will be measured using Sidestream Dark Field imaging.
Time frame: 8 weeks
Change from baseline in transepidermal water loss
Transepidermal water loss will be measured with the Tewameter® TM Hex probe
Time frame: 8 weeks
Change from baseline in skin hydration
The skin hydration will be measured using the Corneometer® CM 825 probeTime
Time frame: 8 weeks
Change from baseline in VEGF-A
Vascular endothelial growth factor A (VEGF-A) levels (in pg/mL) will be determined with ELISA
Time frame: 8 weeks
Change from baseline in Angiopoietin 1
Angiopoietin 1 levels (in pg/mL) will be determined with ELISA
Time frame: 8 weeks
Change from baseline in Angiopoietin 2
Angiopoietin 2 levels (in pg/mL) will be determined with ELISA
Time frame: 8 weeks
Change from baseline in TIE2
TIE 2 levels (in pg/mL) will be determined with ELISA
Time frame: 8 weeks
Plan to share: Undecided
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Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)