Metabolic Acidosis5SNCT06237712
Explorative Study to Investigate the Acid-base Response to Sodium and Potassium Salts in Patients With Chronic Kidney Disease.
A study testing Dietary supplement consisting of 40 mmol/daily of potassium chloride, Dietary supplement consisting of 40 mmol/daily of potassium gluconate and Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate in people with Metabolic Acidosis and CKD, run by Erasmus Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metabolic Acidosis, CKD, Electrolyte and Fluid Balance Conditions
- What is being tested?
- Dietary supplement consisting of 40 mmol/daily of potassium chloride, Dietary supplement consisting of 40 mmol/daily of potassium gluconate and Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteNetherlands
- Study dates
- 26 Jan 2024to Jul 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed 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.
- Being tested
- Dietary supplement consisting of 40 mmol/daily of potassium chloride, Dietary supplement consisting of 40 mmol/daily of potassium gluconate, Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate, Dietary supplement consisting of 40 mmol/daily of sodium chloride, Dietary supplement consisting of 40 mmol/daily of sodium bicarbonate
- Medical subject headings
- Acidosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dietary supplement consisting of 40 mmol/daily of potassium chlorideDietary supplement
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 gluconateDietary supplement
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 bicarbonateDietary supplement
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 chlorideDietary supplement
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 bicarbonateDietary supplement
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 capsDietary supplement
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.
| Study group | Role | What they receive |
|---|---|---|
| Sodium chloride | Active comparator | 40 mmol of oral sodium chloride daily for 5 days Receives: Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of sodium chloride |
| Sodium bicarbonate | Active comparator | 40 mmol of oral sodium bicarbonate daily for 5 days Receives: Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of sodium bicarbonate |
| Potassium chloride | Active comparator | 40 mmol of oral potassium chloride daily for 5 days Receives: Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of potassium chloride |
| Potassium bicarbonate | Active comparator | 40 mmol of oral potassium bicarbonate daily for 5 days Receives: Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate |
| Potassium gluconate | Active comparator | 40 mmol of oral potassium gluconate daily for 5 days Receives: Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of potassium gluconate |
| Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Placebo caps |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: After 5 days of intervention
Secondary outcomes (8)
Plasma electrolyte levels
Na, Cl, K, Mg, Ca, Phosphate (all in mmol/L)
Measured: After 5 days of intervention
Urinary citrate
Urinary citrate in mmol/24h
Measured: After 5 days of intervention
Urinary ammonia
urinary ammonia in mmol/24, calculated using the Berthelot method
Measured: After 5 days of intervention
Titratable acid
Titratable acid = (0.067) × (mLs NaOH (sample titration) - mLs NaOH (blank titration)) × 75/ mLs of sample
Measured: After 5 days of intervention
Net acid excretion
Net acid excretion unit/24h, formula = sum of the titratable acid and concentration of ammonia minus the concentration of bicarbonate.
Measured: After 5 days of intervention
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).
Measured: After 5 days of intervention
Body weight
Weight measured by a scale in kilograms
Measured: After 5 days of intervention
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.
Measured: 2 measurements in the morning and evening for 5 days per treatment repeated for 6 treatments in total
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2024
- Study start26 Jan 2024
- Primary completion21 Mar 2025
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metabolic AcidosisStudies of the same condition, open and under way.
- More trials run by Erasmus Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Single-center, placebo-controlled double-blind randomized crossover study.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 31 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ewout Hoorn, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06237712
- Sponsor's protocol ID
- NL84462.078.23
- Acronym
- 5S
- Status last verified
- Aug 2025
- First submitted
- 25 Jul 2023
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Explorative Study to Investigate the Acid-base Response to Sodium and Potassium Salts in Patients With Chronic Kidney Disease.
- ClinicalTrials.gov ID
- NCT06237712
- Acronym / sponsor ID
- 5S / NL84462.078.23
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 31 participants (estimated)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- 26 Jan 2024 (actual)
- Primary completion
- 21 Mar 2025 (actual)
- Study completion
- Jul 2026 (estimated)
- First posted
- 1 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 6
- Model description
- Single-center, placebo-controlled double-blind randomized crossover study.
| Arm | Type | Receives |
|---|---|---|
| Sodium chloride | Active comparator | Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of sodium chloride40 mmol of oral sodium chloride daily for 5 days |
| Sodium bicarbonate | Active comparator | Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of sodium bicarbonate40 mmol of oral sodium bicarbonate daily for 5 days |
| Potassium chloride | Active comparator | Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of potassium chloride40 mmol of oral potassium chloride daily for 5 days |
| Potassium bicarbonate | Active comparator | Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate40 mmol of oral potassium bicarbonate daily for 5 days |
| Potassium gluconate | Active comparator | Dietary Supplement: Dietary supplement consisting of 40 mmol/daily of potassium gluconate40 mmol of oral potassium gluconate daily for 5 days |
| Placebo | Placebo comparator | Dietary Supplement: Placebo caps |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Dietary supplement consisting of 40 mmol/daily of potassium chlorideThe 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 | Potassium chloride |
| Dietary supplement consisting of 40 mmol/daily of potassium gluconateThe 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 | Potassium gluconate |
| Dietary supplement consisting of 40 mmol/daily of potassium bicarbonateThe 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 | Potassium bicarbonate |
| Dietary supplement consisting of 40 mmol/daily of sodium chlorideThe 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 | Sodium chloride |
| Dietary supplement consisting of 40 mmol/daily of sodium bicarbonateThe 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 | Sodium bicarbonate |
| Placebo capsThe 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 | Placebo |
Primary outcome
Plasma bicarbonate by blood draw
Time frame: After 5 days of intervention
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.
8 secondary outcomes
Plasma electrolyte levels
Time frame: After 5 days of intervention
Urinary citrate
Time frame: After 5 days of intervention
Urinary ammonia
Time frame: After 5 days of intervention
Titratable acid
Time frame: After 5 days of intervention
Net acid excretion
Time frame: After 5 days of intervention
Potential renal acid load
Time frame: After 5 days of intervention
Body weight
Time frame: After 5 days of intervention
Blood pressure
Time frame: 2 measurements in the morning and evening for 5 days per treatment repeated for 6 treatments in total
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Dietary supplement consisting of 40 mmol/daily of potassium chloride, Dietary supplement consisting of 40 mmol/daily of potassium gluconate and Dietary supplement consisting of 40 mmol/daily of potassium bicarbonate in people with Metabolic Acidosis and CKD, run by Erasmus Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Plasma bicarbonate by blood draw (time frame: After 5 days of intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.