Investigations of the Optimum Serum Bicarbonate Level in Renal Disease.

Investigations of the Optimum Serum Bicarbonate Level in Renal Disease

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Chronic Renal Insufficiency
• Intervention / Treatment: Drug: Sodium bicarbonate; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Utah
    • Salt Lake City, Utah, United States, 84148
      • VA Salt Lake City Health Care System, Salt Lake City, UT

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sodium Bicarbonate; Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months	Drug: 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.
Placebo Comparator: Placebo; Participants were prescribed an identical number of placebo tablets had they been assigned to the intervention, and took this daily for six months.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1)	Urinary TGF-b1 is considered a marker of renal fibrosis	The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value between the groups.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1)	KIM-1 is a marker of of kidney injury.	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
Change in Urinary Levels of Neutrophil Gelatinase-associated Lipocalin (NGAL)	NGAL is a marker of kidney injury	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
Change in Urinary Levels of Fibronectin	Fibronectin is a marker of kidney injury.	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
Change in Urinary Albumin Levels	Urinary albumin is a marker of kidney damage	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.
Change in Estimated Glomerular Filtration (eGFR)	eGFR is a measure of kidney function	The mean of the 3-month and 6-month measurements will be compared to the baseline values between the groups.

Collaborators and Investigators

• Sponsor: VA Office of Research and Development
• Investigators: Principal Investigator: Kalani L Raphael, MD, VA Salt Lake City Health Care System, Salt Lake City, UT

Publications and helpful links

General Publications

• Gardner J, Tuttle K, Raphael KL. Influence of Medications Containing Acid Salts on Serum Bicarbonate in CKD. Kidney360. 2020 Mar 31;1(5):330-336. doi: 10.34067/KID.0000532019. eCollection 2020 May 28.

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2012
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: March 27, 2012
• First Submitted That Met QC Criteria: April 5, 2012
• First Posted (Estimate): April 10, 2012

Study Record Updates

• Last Update Posted (Actual): August 28, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency
• Other Study ID Numbers: CLIN-002-11F

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No