Investigations of the Optimum Serum Bicarbonate Level in Renal Disease.

• ClinicalTrials.gov Identifier: NCT01574157
• Recruitment Status: Completed
• First Posted: April 10, 2012
• Results First Posted: August 28, 2019
• Last Update Posted: August 28, 2019
• Sponsor: VA Office of Research and Development
• Information provided by (Responsible Party): VA Office of Research and Development

Tracking Information

• First Submitted Date: March 27, 2012
• First Posted Date: April 10, 2012
• Results First Submitted Date: June 26, 2019
• Results First Posted Date: August 28, 2019
• Last Update Posted Date: August 28, 2019
• Actual Study Start Date: November 5, 2012
• Actual Primary Completion Date: May 1, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 12, 2019)

Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1) [ 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. ]

Urinary TGF-b1 is considered a marker of renal fibrosis

Original Primary Outcome Measures (submitted: April 5, 2012)

Change in Urinary Transforming Growth Factor Beta 1 (TGF-b1) [ Time Frame: The mean of the 3-month and 6-month urinary TGF-b1 measurement will be compared to the baseline value. ]

Urinary TGF-b1 is considered a marker of renal fibrosis

Current Secondary Outcome Measures (submitted: August 12, 2019)

• Change in Urinary Levels of Kidney Injury Molecule-1 (KIM-1) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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

Original Secondary Outcome Measures (submitted: April 5, 2012)

Change in urinary Bb and membrane attack complex (MAC) [ Time Frame: The mean of the 3-month and 6-month urinary Bb and MAC measurements will be compared to the baseline values. ]

These are biomarkers of renal complement system activation

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Investigations of the Optimum Serum Bicarbonate Level in Renal Disease.
• Official Title: Investigations of the Optimum Serum Bicarbonate Level in Renal Disease
• 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.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• Chronic Renal Insufficiency
• Diabetes Mellitus

Intervention

• 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.
• 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.

Study Arms

• Active Comparator: Sodium Bicarbonate
  Participants were prescribed 0.5 meq of sodium bicarbonate per 1 kilogram of lean body weight daily for six months
  Intervention: Drug: Sodium bicarbonate
• 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.
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 5, 2012): 74
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 1, 2018
• Actual Primary Completion Date: May 1, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01574157
• Other Study ID Numbers: CLIN-002-11F
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: No

• Responsible Party: VA Office of Research and Development
• Study Sponsor: VA Office of Research and Development
• Collaborators: Not Provided

Investigators

• Principal Investigator: Kalani L Raphael, MD; VA Salt Lake City Health Care System, Salt Lake City, UT

• PRS Account: VA Office of Research and Development
• Verification Date: August 2019