Chronic Renal Insufficiency, Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to see if treatment with sodium bicarbonate will lower urine levels of proteins that are indicators of kidney damage in people with diabetes who also have chronic kidney disease.
Detailed description
Diabetic chronic kidney disease (CKD) is a common problem in Veterans and progresses to end-stage renal disease in many people. It is important to identify treatment strategies that will help prevent the progression of CKD to overt kidney failure. The purpose of this study is to see if sodium bicarbonate reduces urinary markers of kidney damage in Veterans with diabetic CKD and normal serum bicarbonate levels.
Interventions
DRUGPlacebo
Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months.
DRUGSodium bicarbonate
Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Veteran * Age older than 18 years * Diabetes mellitus * Serum bicarbonate 22 - 28 mmol/L on the most recent measurement within the past six months * Stage 2, 3, or 4 CKD (defined as estimated glomerular filtration rate (eGFR) 15 - 89 ml/min/1.73m2 using the CKD-Epidemiology equation) * Urinary albumin:creatinine ratio \> 30 mg/gm on the most recent sample within the past 12 months.
Exclusion criteria
* Lean body weight \> 100 kg * Use of oral medications typically prescribed to raise low serum bicarbonate levels (i.e. sodium bicarbonate, sodium citrate, potassium citrate). * Serum potassium \< 3.5 meq/L at enrollment visit * Use of 5 or more antihypertensive agents, regardless of the indications of each agent * Systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg at the enrollment or baseline visit * Diagnosis of congestive heart failure with current, active Class III or IV New York Heart Association symptoms. * Significant fluid overload such that it is unsafe in the opinion of the PI for the patient to participate in the trial * chronic gastrointestinal disorder or any other factors judged to be likely to limit adherence to interventions (i.e. alcoholism, a history of missing clinic visits) * Chronic immunosuppressive therapy for transplanted organs or other indications * Individuals who are currently a member of a vulnerable population (I.e. incarcerated, pregnant). 11.Currently participating in another interventional research study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1) | The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value between the groups. | Urinary TGF-b1 is considered a marker of renal fibrosis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1) | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | KIM-1 is a marker of of kidney injury. |
| Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL) | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | NGAL is a marker of kidney injury |
| Change in Urinary Levels of Fibronectin | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | Fibronectin is a marker of kidney injury. |
| Change in Urinary Albumin Levels | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | Urinary albumin is a marker of kidney damage |
| Change in Estimated Glomerular Filtration (eGFR) | The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups. | eGFR is a measure of kidney function |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from VA Salt Lake City Healthcare System from November 2012 to October 2017.
Participants by arm
| Arm | Count |
|---|---|
| Sodium Bicarbonate Sodium bicarbonate: Participants will receive 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily. The total amount will be divided into twice daily doses. | 35 |
| Placebo Placebo: Participants will receive an identical number of placebo tablets had they been assigned to the intervention. Placebo will be divided into twice daily doses and receive this for six months. | 39 |
| Total | 74 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 3 |
| Overall Study | Withdrawal by Subject | 4 | 5 |
Baseline characteristics
| Characteristic | Total | Sodium Bicarbonate | Placebo |
|---|---|---|---|
| Age, Continuous | 72 years STANDARD_DEVIATION 8 | 70 years STANDARD_DEVIATION 8 | 73 years STANDARD_DEVIATION 8 |
| Congestive heart failure | 5 Participants | 1 Participants | 4 Participants |
| Estimated glomerular filtration rate | 51 ml/min/1.73m2 STANDARD_DEVIATION 18 | 50 ml/min/1.73m2 STANDARD_DEVIATION 20 | 52 ml/min/1.73m2 STANDARD_DEVIATION 16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 67 Participants | 32 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Hemoglobin A1c | 7.5 % STANDARD_DEVIATION 1.1 | 7.5 % STANDARD_DEVIATION 1 | 7.6 % STANDARD_DEVIATION 1.3 |
| Lean body weight | 68 kg STANDARD_DEVIATION 9 | 67 kg STANDARD_DEVIATION 8 | 68 kg STANDARD_DEVIATION 9 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 68 Participants | 32 Participants | 36 Participants |
| Region of Enrollment United States | 74 Participants | 35 Participants | 39 Participants |
| Serum potassium | 4.2 meq/L STANDARD_DEVIATION 0.4 | 4.2 meq/L STANDARD_DEVIATION 0.4 | 4.3 meq/L STANDARD_DEVIATION 0.4 |
| Serum total carbon dioxide (CO2) | 24 meq/L STANDARD_DEVIATION 2 | 24 meq/L STANDARD_DEVIATION 3 | 24 meq/L STANDARD_DEVIATION 2 |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 72 Participants | 34 Participants | 38 Participants |
| Systolic blood pressure | 128 mm Hg STANDARD_DEVIATION 12 | 129 mm Hg STANDARD_DEVIATION 12 | 127 mm Hg STANDARD_DEVIATION 11 |
| Total body weight | 101 kg STANDARD_DEVIATION 20 | 100 kg STANDARD_DEVIATION 18 | 101 kg STANDARD_DEVIATION 22 |
| Urinary albumin/creatinine | 121 mg/g | 121 mg/g | 131 mg/g |
| Urinary ammonium | 34 meq/d STANDARD_DEVIATION 20 | 36 meq/d STANDARD_DEVIATION 18 | 33 meq/d STANDARD_DEVIATION 21 |
| Urinary fibronectin/creatinine | 102 ng/mg | 107 ng/mg | 97 ng/mg |
| Urinary kidney injury molecule-1/creatinine | 0.89 ng/mg | 0.91 ng/mg | 0.88 ng/mg |
| Urinary neutrophil gelatinase-associated lipocalin/creatinine | 11.1 ng/mg | 10.5 ng/mg | 11.9 ng/mg |
| Urinary pH | 5.5 units on a scale STANDARD_DEVIATION 0.4 | 5.6 units on a scale STANDARD_DEVIATION 0.4 | 5.4 units on a scale STANDARD_DEVIATION 0.4 |
| Urinary titratable acids | 32 meq/d STANDARD_DEVIATION 15 | 32 meq/d STANDARD_DEVIATION 14 | 31 meq/d STANDARD_DEVIATION 16 |
| Urinary transforming growth factor-B1/creatinine | 112 ng/g | 122 ng/g | 103 ng/g |
| Use of angiotensin converting enzyme-inhibitor (ACE-I) or angiotensin receptor blocker (ARB) | 62 Participants | 28 Participants | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 35 | 0 / 39 |
| other Total, other adverse events | 0 / 35 | 0 / 39 |
| serious Total, serious adverse events | 0 / 35 | 0 / 39 |
Outcome results
Primary
Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1)
Urinary TGF-b1 is considered a marker of renal fibrosis
Time frame: The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value between the groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sodium Bicarbonate | Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1) | 7.6 percent change |
| Placebo | Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1) | -4.4 percent change |
Comparison: The primary analysis compared the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.95% CI: [-9.6, 40.1]
Secondary
Change in Estimated Glomerular Filtration (eGFR)
eGFR is a measure of kidney function
Time frame: The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sodium Bicarbonate | Change in Estimated Glomerular Filtration (eGFR) | 1.96 ml/min per 1.73m2 |
| Placebo | Change in Estimated Glomerular Filtration (eGFR) | -1.41 ml/min per 1.73m2 |
Comparison: The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.95% CI: [-0.05, 6.79]
Secondary
Change in Urinary Albumin Levels
Urinary albumin is a marker of kidney damage
Time frame: The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sodium Bicarbonate | Change in Urinary Albumin Levels | 21.1 percent change |
| Placebo | Change in Urinary Albumin Levels | 11.9 percent change |
Comparison: The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.95% CI: [-24.6, 35.9]
Secondary
Change in Urinary Levels of Fibronectin
Fibronectin is a marker of kidney injury.
Time frame: The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sodium Bicarbonate | Change in Urinary Levels of Fibronectin | 8.8 percent change |
| Placebo | Change in Urinary Levels of Fibronectin | 1.1 percent change |
Comparison: The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.95% CI: [-15.1, 36.5]
Secondary
Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1)
KIM-1 is a marker of of kidney injury.
Time frame: The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Sodium Bicarbonate | Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1) | -11.4 percent change |
| Placebo | Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1) | -1.5 percent change |
Comparison: The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.95% CI: [-38.2, 30.8]
Secondary
Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL)
NGAL is a marker of kidney injury
Time frame: The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Sodium Bicarbonate | Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL) | -28.5 percent change |
| Placebo | Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL) | 5.9 percent change |
Comparison: The main analytic strategy for this secondary outcome was a comparison of the mean change from baseline in the sodium bicarbonate group to the mean change from baseline in the placebo group.95% CI: [-56.3, 4.2]