Clinical trial NCT05966415: Endocalyx for Heart Failure
Official title: Glycocalyx Restoration in Chronic Heart Failure: a Proof of Concept, Randomized, Double-blind, Placebo-controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Chronic Heart Failure
Keywords: Glycocalyx
Glycosaminoglycans
Non-osmotic sodium storage
Chronic heart failure
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2023-07-28
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Maximum age (years): 110
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: randomized, double-blind, placebo-controlled study
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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:

1. To evaluate whether Endocalyx will improve physical limitations and patient-reported outcomes such as fluid overload symptoms and quality of life.
2. To determine the working mechanisms of Endocalyx in heart failure patients.

   1. To determine whether Endocalyx will alter tissue sodium content.
   2. To analyze whether Endocalyx reduces total body water and body weight.
   3. To assess whether Endocalyx affects office blood pressure, 24-hour blood pressure, peripheral resistance and cardiac output.
   4. To assess whether Endocalyx improves microcirculation characteristics.
   5. To evaluate whether Endocalyx reduces systemic inflammation and monocyte activation.
3. To confirm safety of Endocalyx in the heart failure population a. To compare the incidence of (serious) adverse events between Endocalyx and placebo.

Eligibility criteria: Inclusion Criteria:

1. Documented or suspected heart failure with reduced ejection fraction (HFrEF and HFmrEF according to ESC guidelines).
2. 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.
3. Stable diuretic and antihypertensive treatment for the previous 3 weeks.
4. 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:

1. Age \<18 years.
2. Estimated glomerular filtration rate (eGFR) \<15 ml/min/1.73m2 measured by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula.
3. Systolic (\<105 mmHg) or diastolic hypotension (\<60 mmHg) as measured by office blood pressure measurements.
4. Severe symptoms of (orthostatic) hypotension.
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.
9. Planned surgery in the next 8 weeks.
10. Major surgery in the previous 4 weeks.
11. Use of any other investigational drug.
12. Presence of significant comorbidities (e.g., advanced malignancy, advanced liver disease) with a life expectancy of less than 1 year.
13. A psychiatric, addictive or any disorder that compromises ability to give truly informed consent for participation in this study.
14. Known hypersensitivity to seaweed, corn, artichoke, grape, melon or to any of the excipients of Endocalyx.
15. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose galactose malabsorption.

Primary outcomes:
measure: Percent change of NT-proBNP from baseline to week 8 in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 8 weeks
Secondary outcomes:
measure: Change in 24 hour blood pressure, daytime blood pressure, nighttime blood pressure in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 8 weeks
measure: Change in total body water in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 8 weeks
measure: Change in body weight (in kilograms) in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 8 weeks
measure: Change in hemodynamic parameters in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 8 weeks
measure: Concentration change of Adrenomedullin in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 0-8 weeks
measure: Change/difference in ratio of classical (CD14++/CD16-), non-classical (CD14+/CD16++) and intermediate (CD14++/CD16+) monocyte subsets in Endocalyx treated patients when compared with subject receiving Placebo
timeFrame: 0-8 weeks
measure: 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
timeFrame: 8 weeks
measure: Lipopolysaccharide-mediated cytokine secretion of monocytes in vitro in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 8 weeks
measure: Difference in hospitalization rates due to heart failure in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 12 weeks
measure: Distance covered during the 6 minute walking tests in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 8 weeks
measure: Change in self-reported Quality of life in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 8 weeks
measure: Difference in incidence of (serious) adverse events in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 12 weeks
measure: Pharmacokinetics of Endocalyx
timeFrame: 0-8 weeks
measure: Skin sodium content in skin biopsies
timeFrame: 0-8 weeks
measure: monocyte and macrophage expression and density in skin biopsies
timeFrame: 0-8 weeks
measure: Change/difference in blood pressure in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 12 weeks
measure: Difference/Change in 24-hour urine sodium and potassium excretion in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 8 weeks
measure: Plasma aldosterone and renin change/difference in Endocalyx treated patients when compared with subjects receiving Placebo
timeFrame: 8 weeks
measure: Differential treatment effects of Endocalyx in male and female patients
timeFrame: 12 weeks
measure: Percent change in antihypertensive drug dosage or number prescribed
timeFrame: 8 weeks
measure: Percent change in diuretics (dosage or number prescribed)
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Rik Olde Engberink
role: PRINCIPAL_INVESTIGATOR
References: