Kidney TransplantationEarly Phase 1NCT01225796
Study of Sodium Bicarbonate in Kidney Transplant Recipients
A Early Phase 1 study testing Sodium bicarbonate in people with Kidney Transplantation, run by University of Utah at 1 site in United States.
Trial summary
The purpose of this study is to compare the effect of sodium bicarbonate versus no sodium bicarbonate treatment on urinary ammonia levels and urinary transforming growth factor-beta1 (TGF-beta1) excretion in renal transplant patients with low-to-normal serum bicarbonate levels (20 - 28 mmol/L). Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- Sodium bicarbonate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Nov 2012
- Phase
- Early Phase 1
- 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 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Renal transplant recipients
- Age 21-75 years
- Six months since the time of the most recent transplant
- Serum bicarbonate 20-28mM on the two most recent serum measures with the last six months
- Stable creatinine
Who cannot join
- Systolic blood pressure > 140mmHg
- Diastolic blood pressure > 90mmHg
- Known ejection fraction <50%
- Clinical diagnosis of heart failure
- Use of >3 antihypertensive agents
- > 1+ edema
- Use of alkali in the preceding 3 months
- History of noncompliance with clinic visits
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized Trial of Sodium Bicarbonate in Renal Transplant Recipients With Low-normal Serum Bicarbonate Levels
The purpose of this study is to compare the effect of sodium bicarbonate versus no sodium bicarbonate treatment on urinary ammonia levels and urinary transforming growth factor-beta1 (TGF-beta1) excretion in renal transplant patients with low-to-normal serum bicarbonate levels (20 - 28 mmol/L).
Read the detailed description
Renal allograft survival ten years after transplant is only about 50%. In people with non-transplant chronic kidney disease (CKD), sodium bicarbonate treatment seems to delay progressive decline in kidney function in those with low serum bicarbonate levels (metabolic acidosis). This may be because sodium bicarbonate reduces renal ammonia production and hence fibrosis. Observational evidence suggests that people with CKD and low-normal serum bicarbonate levels might also benefit from sodium bicarbonate treatment. TGF-beta1 levels seem to be an important predictor of chronic allograft nephropathy, and alkalinizing agents may have an effect on TFG-beta1 excretion.
Retrospective analysis of participants in the African American Study of Kidney Disease and Hypertension showed the lowest risk of CKD progression was among those having baseline serum bicarbonate levels in the range of 28-30 mmol/L. Recent studies in people with pre-transplant CKD have suggested that increasing low serum bicarbonate levels (< 22 mmol/L) with alkalinizing agents such as sodium bicarbonate and sodium citrate may reduce CKD progression.
Design: this is an open-label randomized study testing the effect of a six-month intervention with sodium bicarbonate 650 mg orally thrice daily versus no sodium bicarbonate treatment on renal ammonia excretion and urinary TGF-beta1.
Visits will occur at baseline, 3 months, and 6 months. At each follow-up visit, the study coordinator or principal investigator will review a medical questionnaire with the participant and collect a sample of blood and urine for analysis of urinary TGF-beta1, metabolic panel, pH, urinary net acid excretion, urinary bicarbonate and urinary ammonia.
- Conditions
- Kidney Transplantation
- Being tested
- Sodium bicarbonate
- Keywords
- Bicarbonate, Chronic allograft nephropathy, Urinary TGF-beta, Urinary acid excretion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium bicarbonateDrug
Sodium bicarbonate 650mg by mouth three times daily for 6 months.
| Study group | Role | What they receive |
|---|---|---|
| Sodium bicarbonate | Experimental | This group will receive oral sodium bicarbonate 650mg three times daily for 6 months. Receives: Drug: Sodium bicarbonate |
| Control | No intervention | This group will not receive any sodium bicarbonate. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Urinary transforming growth factor-beta1
This is considered a surrogate marker of chronic allograft nephropathy (tubulointerstitial fibrosis).
Measured: 6 months
Secondary outcomes (1)
urinary ammonia excretion
a component of urinary acid excretion
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2010 (estimated)
- Study startNov 2010
- Primary completionNov 2012
- Study completionNov 2012
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 Kidney TransplantationStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kalani Raphael, University of Utah
- Investigators
- Kalani L Raphael, MD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01225796
- Sponsor's protocol ID
- 00044216
- Status last verified
- Apr 2016
- First submitted
- 15 Oct 2010
- Last updated
- 6 Apr 2016
- Results posted
- No
- Data monitoring committee
- 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 19608703Amara AB, Sharma A, Alexander JL, Alfirevic A, Mohiuddin A, Pirmohamed M, Close GL, Grime S, Maltby P, Shawki H, Heyworth S, Shenkin A, Smith L, Sharma AK, Hammad A, Rustom R. Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy. Transplantation. 2010 Jan 15;89(1):104-14. doi: 10.1097/TP.0b013e3181bf13d9.
PubMed 20061926Mahajan A, Simoni J, Sheather SJ, Broglio KR, Rajab MH, Wesson DE. Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy. Kidney Int. 2010 Aug;78(3):303-9. doi: 10.1038/ki.2010.129. Epub 2010 May 5.
PubMed 20445497Raphael KL, Wei G, Baird BC, Greene T, Beddhu S. Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans. Kidney Int. 2011 Feb;79(3):356-62. doi: 10.1038/ki.2010.388. Epub 2010 Oct 20.
PubMed 20962743
Study at a glance
From the registry record, last updated by the sponsor on 6 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Sodium Bicarbonate in Renal Transplant Recipients With Low-normal Serum Bicarbonate Levels
- ClinicalTrials.gov ID
- NCT01225796
- Acronym / sponsor ID
- 00044216
- Conditions
- Kidney Transplantation
- Keywords
- Bicarbonate, Chronic allograft nephropathy, Urinary TGF-beta, Urinary acid excretion
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Nov 2012 (actual)
- Study completion
- Nov 2012 (actual)
- First posted
- 21 Oct 2010 (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.
The purpose of this study is to compare the effect of sodium bicarbonate versus no sodium bicarbonate treatment on urinary ammonia levels and urinary transforming growth factor-beta1 (TGF-beta1) excretion in renal transplant patients with low-to-normal serum bicarbonate levels (20 - 28 mmol/L).
Detailed description
Renal allograft survival ten years after transplant is only about 50%. In people with non-transplant chronic kidney disease (CKD), sodium bicarbonate treatment seems to delay progressive decline in kidney function in those with low serum bicarbonate levels (metabolic acidosis). This may be because sodium bicarbonate reduces renal ammonia production and hence fibrosis. Observational evidence suggests that people with CKD and low-normal serum bicarbonate levels might also benefit from sodium bicarbonate treatment. TGF-beta1 levels seem to be an important predictor of chronic allograft nephropathy, and alkalinizing agents may have an effect on TFG-beta1 excretion.
Retrospective analysis of participants in the African American Study of Kidney Disease and Hypertension showed the lowest risk of CKD progression was among those having baseline serum bicarbonate levels in the range of 28-30 mmol/L. Recent studies in people with pre-transplant CKD have suggested that increasing low serum bicarbonate levels (< 22 mmol/L) with alkalinizing agents such as sodium bicarbonate and sodium citrate may reduce CKD progression.
Design: this is an open-label randomized study testing the effect of a six-month intervention with sodium bicarbonate 650 mg orally thrice daily versus no sodium bicarbonate treatment on renal ammonia excretion and urinary TGF-beta1.
Visits will occur at baseline, 3 months, and 6 months. At each follow-up visit, the study coordinator or principal investigator will review a medical questionnaire with the participant and collect a sample of blood and urine for analysis of urinary TGF-beta1, metabolic panel, pH, urinary net acid excretion, urinary bicarbonate and urinary ammonia.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sodium bicarbonate | Experimental | Drug: Sodium bicarbonateThis group will receive oral sodium bicarbonate 650mg three times daily for 6 months. |
| Control | No intervention | –This group will not receive any sodium bicarbonate. |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Renal transplant recipients
- Age 21-75 years
- Six months since the time of the most recent transplant
- Serum bicarbonate 20-28mM on the two most recent serum measures with the last six months
- Stable creatinine
Key exclusion criteria (8 listed)
- Systolic blood pressure > 140mmHg
- Diastolic blood pressure > 90mmHg
- Known ejection fraction <50%
- Clinical diagnosis of heart failure
- Use of >3 antihypertensive agents
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 bicarbonateSodium bicarbonate 650mg by mouth three times daily for 6 months. | Drug | Sodium bicarbonate |
Primary outcome
Urinary transforming growth factor-beta1
Time frame: 6 months
This is considered a surrogate marker of chronic allograft nephropathy (tubulointerstitial fibrosis).
1 secondary outcome
urinary ammonia excretion
Time frame: 6 months
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 6 Apr 2016.
- 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 20061926Amara AB, Sharma A, Alexander JL, Alfirevic A, Mohiuddin A, Pirmohamed M, Close GL, Grime S, Maltby P, Shawki H, Heyworth S, Shenkin A, Smith L, Sharma AK, Hammad A, Rustom R. Randomized controlled trial: lisinopril reduces proteinuria, ammonia, and renal polypeptide tubular catabolism in patients with chronic allograft nephropathy. Transplantation. 2010 Jan 15;89(1):104-14. doi: 10.1097/TP.0b013e3181bf13d9.
- Background: PubMed 20445497Mahajan A, Simoni J, Sheather SJ, Broglio KR, Rajab MH, Wesson DE. Daily oral sodium bicarbonate preserves glomerular filtration rate by slowing its decline in early hypertensive nephropathy. Kidney Int. 2010 Aug;78(3):303-9. doi: 10.1038/ki.2010.129. Epub 2010 May 5.
- Background: PubMed 20962743Raphael KL, Wei G, Baird BC, Greene T, Beddhu S. Higher serum bicarbonate levels within the normal range are associated with better survival and renal outcomes in African Americans. Kidney Int. 2011 Feb;79(3):356-62. doi: 10.1038/ki.2010.388. Epub 2010 Oct 20.
Related trials for Kidney Transplantation
Enrolling by invitation
Online Exercise Program for Transplant Patients: A Pilot Study
Kidney Transplantation, Physical Function
RecruitingPhase 2
A Study of Mezagitamab in Adults With Late Antibody-Mediated Rejection (AMR) After a Kidney Transplant
Antibody-Mediated Rejection (AMR)
Not yet recruiting
Hypothermic Kidney Machine Perfusion With Omnisol
End Stage Renal Disease (ESRD), Kidney Transplant
Not yet recruitingEarly Phase 1
Biomarker-Guided Mycophenolate Mofetil Elimination in Low-Risk Older Adult Kidney Transplant Recipients
Kidney Transplant Recipient
Recruiting
Non-Invasive Monitoring of Pediatric Kidney Transplant Recipients and Immunosuppression Personalization: an Open-labeled Multicenter Randomized Controlled Study
Pediatric Kidney Disease, Transplant;Failure,Kidney
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.
Kalani L Raphael, MD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Sodium bicarbonate in people with Kidney Transplantation, run by University of Utah at 1 site in United States.
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 5 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 6 Apr 2016. 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 United States. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 transforming growth factor-beta1 (time frame: 6 months). 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 NCT01225796, 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 6 Apr 2016.