Explorative Study to Investigate the Acid-base Response to Sodium and Potassium Salts in Patients With Chronic Kidney Disease.

CKD Clinical Trial

— 5S  

Official title:

Explorative Study to Investigate the Acid-base Response to Sodium and Potassium Salts in Patients With Chronic Kidney Disease.

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06237712
• Other study ID #: NL84462.078.23
• Status: Enrolling by invitation
• Phase: N/A
• Start date: January 26, 2024
• Est. completion date: July 2026

Study information

• Verified date: February 2024
• Source: Erasmus Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

With this research the investigators want to study how patients with chronic kidney disease respond to different sodium- and potassium salts. Potassium salts can prevent kidney damage and cardiovascular disease, however patients with chronic kidney disease can responds differently. Extra potassium can increase the amount of potassium in the blood and extra chloride can cause acidosis. With this study the investigators will gain more insight in how patients with chronic kidney disease respond to sodium and potassium salts and which one is more favorable.This information can then be used to guide the application of salt substitutes and dietary adjustments in patients with chronic kidney disease.

Description:

Rationale: Patients with chronic kidney disease (CKD) consume a low potassium diet which is associated with progressive CKD and cardiovascular disease. Increasing dietary potassium intake to recommended levels may therefore improve cardiorenal outcomes, but the response to increased potassium intake in patients with CKD is unclear. Therefore, the investigators recently tested the response to 40 mmol potassium chloride in patients with CKD and showed that this is generally well-tolerated. However, patients did develop mild hyperchloremic metabolic acidosis, which may offset the beneficial effects of potassium. The investigators hypothesize that this is a form of chloride-induced acidosis that may be prevented by giving potassium with a different anion than chloride. To further investigate this, the investigators propose to test the response to five different sodium and potassium salts in patients with CKD. These results should inform us on how to best correct a potassium-deficient diet in patients with CKD.

Objective: To test the effects of five different sodium and potassium salts in patients with CKD.

Study design: Investigator-initiated, single-center, placebo-controlled double-blind randomized crossover study.

Study population: Adult outpatients (age ≥ 18 years) with CKD stage G3b or G4 using renin-angiotensin-aldosterone system inhibitors (RAAS-I).

Intervention: Capsules with 40 mmol potassium chloride, potassium bicarbonate, potassium gluconate, sodium bicarbonate, sodium chloride or placebo (3 x 3 capsules per day).

Main study parameters/endpoints: Difference in plasma bicarbonate after treatment.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The study lasts 6 weeks and consists of 7 visits that will consist of blood sampling, 24-hour urine collection and spot urine collection. We will also provide an automated blood pressure measuring device for at home blood pressure measurements. Although these procedures are time-consuming and may be experienced as burdensome, they are all routine clinical measurements and safe. Patients may experience a pill-burden. The two risks of the salt supplements are hyperkalemia (with potassium salts) and hypertension (with sodium salts). Based on our previous studies a minority of patients is expected to develop these side-effects (< 12%). Safety measures to prevent, monitor and treat these side-effects are included in the study protocol. There are no direct benefits for patients participating in this trial, but the results will contribute to a better understanding on the feasibility of dietary modifications and salt substitution in patients with CKD to improve health. Patients will be reimbursed for their participation.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 31
• Est. completion date: July 2026
• Est. primary completion date: July 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Adult patients (= 18 years)

• CKD G3b or G4 (44 - 15 ml/min/1.73 m2)

• Use of RAAS-I (ACE-inhibitor or angiotensin receptor blocker, ARB)

Exclusion Criteria:

• Use of any of the following drugs or supplements: mineralocorticoid receptor antagonists, potassium-sparing diuretics, oral potassium binders, immunosuppressive medication, tolvaptan, acetazolamide, topiramate, sodium bicarbonate.

• Patients using double RAAS blockade (i.e., ACE-inhibitor + ARB).

• Metabolic alkalosis (plasma bicarbonate >27 mmol/L) at last outpatient visit

• Kidney transplant recipients

• Patients with an active gastro-intestinal ulcer

• Patients with previous history of ventricular cardiac arrhythmia

• Patients with a life expectancy < 6 months

• Incapacitated subjects or subjects who are deemed unfit to adequately adhere to instructions from the research team

• Women who are pregnant, breastfeeding or consider pregnancy in the coming 7 weeks

• Patients with chronic respiratory acidosis in previous medical history

• Hyperkalemia (plasma potassium >5.5 mmol/L) at V0

Related Conditions & MeSH terms

• Acidosis
• CKD
• Electrolyte and Fluid Balance Conditions
• Kidney Diseases
• Metabolic Acidosis
• Renal Insufficiency, Chronic

Intervention

Dietary Supplement:
• Dietary supplement consisting of 40 mmol/daily of potassium chloride
The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
• Dietary supplement consisting of 40 mmol/daily of potassium gluconate
The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
• Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate
The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
• Dietary supplement consisting of 40 mmol/daily of sodium chloride
The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
• Dietary supplement consisting of 40 mmol/daily of sodium bicarbonate
The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.
• Placebo caps
The supplements are delivered in plain vegetable 00 caps, stabelizing additives are potatostarch, sunflower lecithine and sunflower oil. The capsuels are free of titanium oxide and suited for human consumption.

Locations

Country	Name	City	State
Netherlands	ErasmusMC	Rotterdam	Zuid-Holland

Sponsors (1)

Lead Sponsor	Collaborator
Erasmus Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma bicarbonate by blood draw	The absolute difference per treatment group in measured plasma bicarbonate after treatment.; After each treatment of 5 days, plasma bicarbonate will be measured by blood sampling.; The difference between the groups (treatments) will be the main outcome and comparator.	After 5 days of intervention
Secondary	Plasma electrolyte levels	Na, Cl, K, Mg, Ca, Phosphate (all in mmol/L)	After 5 days of intervention
Secondary	Urinary citrate	Urinary citrate in mmol/24h	After 5 days of intervention
Secondary	Urinary ammonia	urinary ammonia in mmol/24, calculated using the Berthelot method	After 5 days of intervention
Secondary	Titratable acid	Titratable acid = (0.067) × (mLs NaOH (sample titration) - mLs NaOH (blank titration)) × 75/ mLs of sample	After 5 days of intervention
Secondary	Net acid excretion	Net acid excretion unit/24h, formula = sum of the titratable acid and concentration of ammonia minus the concentration of bicarbonate.	After 5 days of intervention
Secondary	Potential renal acid load	PRAL (mEq/d) = 0.49 × protein (g/d) + 0.037 × phosphate (mg/d) - 0.021 × potassium (mg/d) - 0.026 × magnesium (mg/d) - 0.013 × calcium (mg/d).	After 5 days of intervention
Secondary	Body weight	Weight measured by a scale in kilograms	After 5 days of intervention
Secondary	Blood pressure	Systolic and diastolic blood pressure measured 2 times daily during the study, so 20 times during the 5 days of supplement usage. Measurements will be done in the morning and evening measured twice in seated position with an automatic blood pressure monitor.	2 measurements in the morning and evening for 5 days per treatment repeated for 6 treatments in total