Treatment Resistant Hypertension
Conditions
Keywords
Glycocalyx, Glycosaminoglycans, non-osmotic sodium storage, hypertension
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTEndocalyx Pro
4 capsules once daily OR 2 capsules twice daily
OTHERPlacebo
4 capsules once daily OR 2 capsules twice daily
Sponsors
Dutch Heart Foundation
Dutch Kidney Foundation
Microvascular Health Solutions LLC
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomized, double-blind, placebo-controlled study
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in 24-hour systolic blood pressure | 12 weeks | We will perform an uncorrected analysis and an analysis that is corrected for the reported and measured changes in antihypertensive medication use. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from baseline in microvascular flow index | 12 weeks | The microvascular flow index will be measured using Sidestream Dark Field imaging. |
| Change from baseline in skin hydration | 12 weeks | The skin hydration will be measured using the Corneometer® CM 825 probe |
| Change from baseline in total body water | 12 weeks | The change in total body water (liter) will be measured using the bioelectrical impendance analysis |
| Incidence of adverse events in the Endocalyx group compared to the placebo group | 12 weeks | — |
| Change from baseline in muscle sodium content | 12 weeks | Muscle sodium content will measured using a 7T sodium MRI |
| Change from baseline in skin water content | 12 weeks | Skin water content will measured using a 7T H-MRI |
| 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 | 12 weeks | 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. |
| Percentage of patients achieving a seated office blood pressure <140/90 mmHg after intervention | 12 weeks | Participants achieved a response if the systolic blood pressure is below 140 mmHg and the diastolic blood pressure is below 90 mmHg |
| 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 | 12 weeks | The total vessel density and perfused vessel density will be measured using Sidestream Dark Field imaging. |
| Change from baseline in proportion of perfused vessels | 12 weeks | The proportion of perfussed vessels will be measured using Sidestream Dark Field imaging. |
| Change from baseline in microvascular health score | 12 weeks | The microvascular health score will be measured using Sidestream Dark Field imaging. |
| Change from baseline in heart rate | 12 weeks | The heart rate will be measured using the Nexfin device |
| Change from baseline in total peripheral resistance | 12 weeks | The total pheripheral resistance will be measured using the Nexfin device |
| Change from baseline in cardiac output | 12 weeks | The cardiac output will be measured using the Nexfin device |
| Change from baseline in quality of life | 12 weeks | Quality of life will be evaluated by the SF-36 questionnaire. |
| The potential impact of Endocalyx on long-term cardiovascular protection and health care costs. | 12 weeks | 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). |
| Change from baseline in skin sodium content | 12 weeks | Skin sodium content will measured using a 7T sodium MRI |
| Change from baseline in muscle water content | 12 weeks | Muscle water content will measured using a 7T H-MRI |
| Change from baseline in transepidermal water loss | 12 weeks | Transepidermal water loss will be measured with the Tewameter® TM Hex probe |
Other
| Measure | Time frame | Description |
|---|---|---|
| To assess whether kidney function modulate the effect of Endocalyx on blood pressure. | 12 weeks | The association between kidney function and the effect of endocalyx on blood pressure. |
| To assess whether sex modulate the effect of Endocalyx on blood pressure. | 12 weeks | The association between sex and the effect of endocalyx on blood pressure. |
| To assess whether sodium intake, measured using 24-hour urine collection, modulate the effect of Endocalyx on blood pressure. | 12 weeks | 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. |
Countries
Netherlands
Contacts
Primary ContactRik Olde Engberink, MD PhD
Backup ContactSanédy Simon, MD
Outcome results
None listed