Primary Objective: • To assess whether the food supplement Endocalyx lowers blood pressure in patients with treatment resistant hypertension.Secondary Objectives: • To study the effect of Endocalyx on office blood pressure and 24-hour blood pressure…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
hypertensie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
24-hour systolic blood pressure
Secondary outcome
Secondary outcomes will be used to investigate the mechanism by which Endocalyx
may improve hypertension and to assess the safety in patients with treatment
resistant hypertension:
- 24-hour blood pressure parameters: daytime blood pressure, night-time blood
pressure, dipping status
- Office blood pressure.
- Percentage of patients that needed additional antihypertensive drugs during
the study
- Percentage of patients that required lowering of antihypertensive drugs
during the study
- Percentage of patients with an office blood pressure <140/90 mmHg
- Total body water and body weight.
- Hemodynamic parameters: heart rate, cardiac output and total peripheral
resistance.
- Microcirculation analysis
- 36-item short form health survey (SF-36)
- EQ-5D-5L questionnaire
- Incidence of (serious) adverse events.
- Skin sodium content as measured with 23Na-MRI
- The modulating effect of sodium intake, sex and kidney function on the
abovementioned parameters
Background summary
Hypertension is the most important risk factor for cardiovascular disease and
all-cause mortality worldwide. Although antihypertensive therapy is readily
available, half of the patients with hypertension have an uncontrolled blood
pressure (BP). If BP is uncontrolled despite using >=3 antihypertensive drugs,
it is considered to be treatment resistant hypertension (TRH). Among treated
adults with hypertension the prevalence of TRH is 10-15%, which equals 675,000
patients in the Netherlands. Subjects with TRH have a 50% higher risk for
cardiovascular or renal disease, or death than subjects with normal
hypertension. Currently, no treatment is available for subjects with
uncontrolled BP despite maximum drug therapy and invasive interventions such as
renal nerve ablation or carotid baroreceptor activation therapy are considered
in a research setting.
Besides antihypertensive drugs, lifestyle changes are crucial to control BP.
Reduction of dietary sodium intake is by far the most effective lifestyle
intervention and can lower systolic/diastolic BP with 23/9 mmHg in subjects
with TRH. However, because of large amounts of sodium in processed foods,
patients often fail to adhere to a lifelong low sodium diet, which is an
important cause of TRH. For example, the average sodium intake in TRH patients
is 187 mmol/day while a daily intake <87 mmol is advised. We therefore need a
new treatment, which ideally targets the sodium overload and sodium sensitivity
of BP in TRH patients.
Tissue sodium accumulation
Long-term sodium balance studies demonstrated that sodium can be osmotically
inactivated by negatively-charged glycosaminoglycans that are present in the
skin and the glycocalyx, an intravascular layer of glycosaminoglycans. As a
result, sodium retention is not accompanied by water retention or a BP
increase. In addition, the glycocalyx prevents sodium to be transported to the
skin where high sodium content impairs microcirculatory function.
Hypertensive patients have a damaged glycocalyx and are thus not able to
neutralize the negative effects of sodium excess or prevent sodium leakage to
the skin, which contributes to sodium sensitivity of BP. We previously
demonstrated that glycocalyx restoration with oral glycosaminoglycans reduced
BP in subjects with proteinuria. We expect that glycosaminoglycan
supplementation will restore the glycocalyx, prevent skin sodium accumulation
and lower BP in TRH subjects.
Endocalyx is food supplement that consists of polysaccharides, amino sugars and
antioxidants, which has been designed to restore the glycocalyx. The
polysaccharides are a natural component of the glycocalyx and are adsorbed by
the glycocalyx. Amino sugars, such as glucosamine, are precursors for the
biosynthesis of polysaccharides and antioxidants protect the endothelial
polysaccharides from breakdown. Endocalyx has demonstrated to improve
microvascular health by 50% and decrease the perfused boundary region, which
indicates improved glycocalyx health.
Potential impact on cardiovascular burden of disease
In the Netherlands, approximately 675,000 patients have TRH. The average annual
incidence of cardiovascular events and mortality in these patients is around
4.65% and 3.45%, respectively. When extrapolating these proportions to the
Dutch TRH population, this would account for approximately 31,388
cardiovascular events and 23,288 deaths annually.
Previous studies have demonstrated that the expected 8 mmHg decrease in
systolic BP by Endocalyx will result in a 27% decrease in stroke, 17% decrease
in coronary events and heart failure, and 13% decrease in cardiovascular
mortality Consequently, about 4,118 cardiovascular events and 878 deaths could
be prevented annually in the population of subjects with TRH.
Study objective
Primary Objective:
• To assess whether the food supplement Endocalyx lowers blood pressure in
patients with treatment resistant hypertension.
Secondary Objectives:
• To study the effect of Endocalyx on office blood pressure and 24-hour blood
pressure profiles (daytime BP, night-time BP, dipping status) in subjects with
treatment resistant hypertension.
• To evaluate the percentage of patients achieving an office blood pressure
<140/90 mmHg.
• To assess whether sodium intake, sex or kidney function modulates the effect
of Endocalyx on blood pressure.
• To define the effect of Endocalyx on microcirculatory health in subjects with
treatment resistant hypertension.
• To assess the effect of Endocalyx on total peripheral resistance in treatment
resistant hypertension subjects.
• To assess whether Endocalyx improves quality of life.
• To estimate the potential impact of Endocalyx on long-term cardiovascular
protection and health care costs.
*
Study design
We will use a proof-of-principle randomized, placebo-controlled, double-blind
trial to investigate the effects of Endocalyx in patients with treatment
resistant hypertension. Patients will be randomly assigned (1:1) to the food
supplement Endocalyx or placebo, 4 capsules per day, in addition to their
current medication for 12 weeks. Patients will be recruited from the Internal
Medicine outpatient clinics of Amsterdam UMC, Onze Lieve Vrouwe Gasthuis (OLVG)
and Flevoziekenhuis.
Patients will make a total of 5 study visits and we will conduct 3 scheduled
telephone calls. All study visits will be conducted at Amsterdam UMC, location
AMC.
Intervention
Patients will be randomly assigned to the food supplement Endocalyx or placebo
in addition to their current medication for 12 weeks. Patients in the Endocalyx
and placebo arm will receive 4 capsules per day. This treatment will be double
blinded.
Study burden and risks
The overall risk of the Endocalyx food supplement is low. The individual
ingredients of the supplement are already used as dietary supplements. Large
randomized controlled trials with the individual ingredients, some with higher
dosages of the ingredients than in the Endocalyx supplement, revealed no major
adverse effects and showed the safety of the individual ingredients. In the
pilot study with the supplement, no serious adverse effects were reported. One
side effect that was reported was dizziness because of the effect on reducing
blood pressure. The blood pressure is measured at every study visit and the
dosages of the anti-hypertensive medicine can be altered if needed. Moreover,
the occurrence of adverse effects is documented and evaluated at the end of
every month. Patients are provided with the telephone number of the
investigator that they can call in the case of a serious adverse event.
Meibergdreef 9
Amsterdam 1105 AZ
NL
Meibergdreef 9
Amsterdam 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
1. Treatment resistant hypertension defined as
a. an uncontrolled office BP (>=140/90 mmHg).
b. 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 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.
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 mm Hg or a diastolic
blood pressure of at least 110 mm Hg (if the patient did not take their
regularly scheduled blood pressure medication prior to the visit, a blood
pressure re-test is allowed within 2 days.
4. Known secondary hypertension
o Obstructive sleep apnea syndrome
o Pheochromocytoma
o Primary hyperaldosteronism
o Renal artery stenosis
o Cushing syndrome
o Uncontrolled or untreated hyperthyroidism
o Aortic coarctation
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). Acceptable methods of contraception for female
patients enrolled in the study include the following:
o Surgical sterilization (tubal ligation);
o Intrauterine device for at least 12 weeks before screening;
o Hormonal contraception (oral, implant, injection, ring, or patch) for at
least 12 weeks before screening; or
o Diaphragm used in combination with spermicide
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.
15. Bekende overgevoeligheid voor zeewier, maïs, artisjok, druif, meloen of
voor één van de hulpstoffen van 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.
18. (Only applicable to participants interested in the additional measurements
using the 7T sodium MRI ) Known contra-indication for MRI scans. Metallic
foreign body, certain drug pumps, hydrocephalus pump, external prosthesis (e.g.
artificial limb), intrauterine device, vascular clips/stents/pumps, cardiac
implantable devices, neuro-stimulator, artificial valves, implanted lenses,
prosthesis or cochlear implants, bones screws, plates, claustrophobia and
orthopnea might be considered a contra-indication for MRI. In all of these
cases, the MR operator will search MRISafety.com to see if the person can be
scanned safely. If it is not clear whether the subject can be safely scanned
with the 7T MRI, a colleague from Spinoza will be contacted to discuss whether
this patient can be scanned safely.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL85685.018.24 |