Chronic Kidney DiseaseBICNCT02896309
The Effect of Correction of Metabolic Acidosis in CKD on Intrarenal RAS Activity
A study testing Sodium bicarbonate and Sodium chloride in people with Chronic Kidney Disease, run by Erasmus Medical Center at 1 site in Netherlands.
Trial summary
This study evaluates the effect of oral sodium bicarbonate treatment on the intrarenal renin-angiotensin-system in adult patients with a metabolic acidosis and chronic kidney disease. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Chronic Kidney Disease
- What is being tested?
- Sodium bicarbonate and Sodium chloride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteNetherlands
- Study dates
- Sep 2016to 27 Dec 2018
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- male or female adult (≥18 years)
- chronic kidney disease stage 4, i.e. estimated glomerular filtration rate (MDRD) 15-30 ml/min
- plasma bicarbonate concentration of 15-24 meq/L
Who cannot join
- bicarbonate level >24 meq/L or <15 meq/L, the latter because in that case it seems highly recommended to start sodium bicarbonate suppletion and not to postpone this
- sodium bicarbonate use in the 1 month preceding the study
- heart failure
- liver cirrhosis
- blood pressure >140/90 mmHg despite the use of 3 different antihypertensives
- a kidney transplant in situ
- a history of nonadherence to medication
- use of calcineurin inhibitors (these immunosuppressive drugs are known to induce metabolic acidosis and influence electrolytes and acid-base balance)
Trial locations and contacts
1 site in 1 country.
About this study
This study evaluates the effect of oral sodium bicarbonate treatment on the intrarenal renin-angiotensin-system in adult patients with a metabolic acidosis and chronic kidney disease. This treatment is compared to sodium chloride treatment, which serves as control for increased sodium-intake and no treatment, which serves as time-control.
Read the detailed description
In chronic kidney disease (CKD), as glomerular filtration rate decreases, excretion of hydrogen ions fails, leading to progressive metabolic acidosis (arterial pH < 7.35 and a serum bicarbonate concentration < 22 meq/L). Metabolic acidosis enhances further progression of CKD. It is known that the intrarenal renin-angiotensin system (RAS) is stimulated during metabolic acidosis, but it's specific role in the renal response on changes in the acid-base balance is unknown. Correction of metabolic acidosis by administration of bicarbonate is a common intervention in patients with metabolic acidosis due to chronic kidney disease. It is proven to slow down progression of CKD. There is no knowledge on the effect this therapy has on the intrarenal RAS. Since acidosis does not change serum renin levels, and bicarbonate therapy has no effect on blood pressure, it seems to have no effect on the systemic RAS. The investigators hypothesize that bicarbonate therapy diminishes intrarenal RAS activity without affecting the systemic RAS.
- Conditions
- Chronic Kidney Disease
- Being tested
- Sodium bicarbonate, Sodium chloride
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium bicarbonateDietary supplement
Sodium chlorideDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Sodium bicarbonate | Experimental | Oral sodium bicarbonate tablets three times daily 1000mg Receives: Dietary Supplement: Sodium bicarbonate |
| Sodium chloride | Active comparator | Oral sodium chloride capsules two times daily 1000mg Receives: Dietary Supplement: Sodium chloride |
| No treatment | No intervention | No treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary renin concentration
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Sep 2016 (estimated)
- Study startSep 2016
- Primary completion27 Dec 2018
- Study completion27 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Chronic Kidney DiseaseStudies 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Erasmus Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ewout Hoorn, Erasmus Medical Center
- Investigators
- Ewout J Hoorn, MD, PhD, Principal investigator, Erasmus Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02896309
- Sponsor's protocol ID
- NL44415.078.13
- Acronym
- BIC
- Status last verified
- Jun 2019
- First submitted
- 18 Aug 2016
- Last updated
- 20 Jun 2019
- Results posted
- No
Publications
de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009 Sep;20(9):2075-84. doi: 10.1681/ASN.2008111205. Epub 2009 Jul 16.
PubMed 19608703Ng HY, Chen HC, Tsai YC, Yang YK, Lee CT. Activation of intrarenal renin-angiotensin system during metabolic acidosis. Am J Nephrol. 2011;34(1):55-63. doi: 10.1159/000328742. Epub 2011 Jun 10.
PubMed 21659740Nagami GT. Role of angiotensin II in the enhancement of ammonia production and secretion by the proximal tubule in metabolic acidosis. Am J Physiol Renal Physiol. 2008 Apr;294(4):F874-80. doi: 10.1152/ajprenal.00286.2007. Epub 2008 Feb 20.
PubMed 18287403Henger A, Tutt P, Riesen WF, Hulter HN, Krapf R. Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients. J Lab Clin Med. 2000 Nov;136(5):379-89. doi: 10.1067/mlc.2000.110371.
PubMed 11079465
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Correction of Metabolic Acidosis in CKD on Intrarenal RAS Activity
- ClinicalTrials.gov ID
- NCT02896309
- Acronym / sponsor ID
- BIC / NL44415.078.13
- Conditions
- Chronic Kidney Disease
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Erasmus Medical CenterUniversity, hospital or other
- Study start
- Sep 2016 (actual)
- Primary completion
- 27 Dec 2018 (actual)
- Study completion
- 27 Dec 2018 (actual)
- First posted
- 12 Sep 2016 (estimated)
- 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.
This study evaluates the effect of oral sodium bicarbonate treatment on the intrarenal renin-angiotensin-system in adult patients with a metabolic acidosis and chronic kidney disease. This treatment is compared to sodium chloride treatment, which serves as control for increased sodium-intake and no treatment, which serves as time-control.
Detailed description
In chronic kidney disease (CKD), as glomerular filtration rate decreases, excretion of hydrogen ions fails, leading to progressive metabolic acidosis (arterial pH < 7.35 and a serum bicarbonate concentration < 22 meq/L). Metabolic acidosis enhances further progression of CKD. It is known that the intrarenal renin-angiotensin system (RAS) is stimulated during metabolic acidosis, but it's specific role in the renal response on changes in the acid-base balance is unknown. Correction of metabolic acidosis by administration of bicarbonate is a common intervention in patients with metabolic acidosis due to chronic kidney disease. It is proven to slow down progression of CKD. There is no knowledge on the effect this therapy has on the intrarenal RAS. Since acidosis does not change serum renin levels, and bicarbonate therapy has no effect on blood pressure, it seems to have no effect on the systemic RAS. The investigators hypothesize that bicarbonate therapy diminishes intrarenal RAS activity without affecting the systemic RAS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sodium bicarbonate | Experimental | Dietary Supplement: Sodium bicarbonateOral sodium bicarbonate tablets three times daily 1000mg |
| Sodium chloride | Active comparator | Dietary Supplement: Sodium chlorideOral sodium chloride capsules two times daily 1000mg |
| No treatment | No intervention | –No treatment |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- male or female adult (≥18 years)
- chronic kidney disease stage 4, i.e. estimated glomerular filtration rate (MDRD) 15-30 ml/min
- plasma bicarbonate concentration of 15-24 meq/L
Key exclusion criteria (8 listed)
- bicarbonate level >24 meq/L or <15 meq/L, the latter because in that case it seems highly recommended to start sodium bicarbonate suppletion and not to postpone this
- sodium bicarbonate use in the 1 month preceding the study
- heart failure
- liver cirrhosis
- blood pressure >140/90 mmHg despite the use of 3 different antihypertensives
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 |
|---|---|---|
| Sodium bicarbonate | Dietary supplement | Sodium bicarbonate |
| Sodium chloride | Dietary supplement | Sodium chloride |
Primary outcome
Urinary renin concentration
Time frame: 4 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jun 2019.
- Background: PubMed 19608703de Brito-Ashurst I, Varagunam M, Raftery MJ, Yaqoob MM. Bicarbonate supplementation slows progression of CKD and improves nutritional status. J Am Soc Nephrol. 2009 Sep;20(9):2075-84. doi: 10.1681/ASN.2008111205. Epub 2009 Jul 16.
- Background: PubMed 21659740Ng HY, Chen HC, Tsai YC, Yang YK, Lee CT. Activation of intrarenal renin-angiotensin system during metabolic acidosis. Am J Nephrol. 2011;34(1):55-63. doi: 10.1159/000328742. Epub 2011 Jun 10.
- Background: PubMed 18287403Nagami GT. Role of angiotensin II in the enhancement of ammonia production and secretion by the proximal tubule in metabolic acidosis. Am J Physiol Renal Physiol. 2008 Apr;294(4):F874-80. doi: 10.1152/ajprenal.00286.2007. Epub 2008 Feb 20.
- Background: PubMed 11079465Henger A, Tutt P, Riesen WF, Hulter HN, Krapf R. Acid-base and endocrine effects of aldosterone and angiotensin II inhibition in metabolic acidosis in human patients. J Lab Clin Med. 2000 Nov;136(5):379-89. doi: 10.1067/mlc.2000.110371.
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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.
Ewout J Hoorn, MD, PhD principal investigator
Erasmus Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sodium bicarbonate and Sodium chloride in people with Chronic Kidney Disease, 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 8 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: finished, as of the sponsor's last update on 20 Jun 2019. 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. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Urinary renin concentration (time frame: 4 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02896309, which also lists 4 linked publications.
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 20 Jun 2019.