Reducing Dietary Acid With Food Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD) (ReDACKD)

Reducing Dietary Acid With Fruit and Vegetables Versus Oral Alkali in People With Chronic Kidney Disease (ReDACKD) Feasibility Trial

Metabolic acidosis is a common problem that occurs with worsening chronic kidney disease. Dietary acid can build up when the kidneys are not working well. This can be associated with a higher risk of worsening kidney function and death. The usual treatment is a medication called sodium bicarbonate which works to balance the acids in the body. The medication however often does not work and causes side effects. Consumption of alkalizing fruit and vegetables may work as a treatment for metabolic acidosis. This trial is being done to see if fruit and vegetables, provided via home delivery, can become a viable management for metabolic acidosis in patients with chronic kidney disease.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Diseases; Metabolic Acidosis
• Intervention / Treatment: Dietary supplement: Alkalizing Fruit and Vegetables; Drug: Sodium bicarbonate

Detailed Description

Metabolic acidosis is a common complication of advanced chronic kidney disease (CKD). As kidney function declines, the ability to excrete excess dietary acid is reduced. This can lead to the development of metabolic acidosis, an imbalance in the body's acid-base balance. Metabolic acidosis is associated with a higher risk of CKD progression and mortality. Typical treatment includes an oral alkali, such as sodium citrate or sodium bicarbonate. Recent studies have shown that the treatment of metabolic acidosis can reduce the decline in kidney function and potentially prevent progression of CKD to dialysis. Treatment rates with an oral alkali are low because the treatments are ineffective, often poorly tolerated, and may be associated with net harm. Base producing fruit and vegetables are a potential treatment of metabolic acidosis by reducing the dietary contribution to overall acid load that must be managed by the kidneys. A recent systematic review and meta-analysis of clinical trials using oral alkali supplements or reduction in dietary acid intake using fruits and vegetables, when compared to no treatment, usual care or placebo found that these treatments increased serum bicarbonate and slowed the decline of kidney function. Fruit and vegetables are an effective and well-tolerated therapy for the treatment of metabolic acidosis in CKD. While oral alkali therapy has known adverse effects, important limitations also exist in the widespread applicability of fruit and vegetables as a treatment for metabolic acidosis. Only 2 single center randomized trials have examined the efficacy of fruit and vegetables for the management for acidosis. This dual-center trial will be the first randomized trial in Canada to evaluate the feasibility of providing fruit and vegetables via home delivery to patients for the management of metabolic acidosis in CKD. This study will be critical in designing a pan-Canadian phase 3 trial testing the efficacy of alkalizing fruit and vegetable provision on slowing the progression of CKD.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Rebecca Mollard, PhD; Phone Number: 204-631-3834; Email: rmollard@sogh.mb.ca
• Study Contact Backup: Name: Katrina Cachero, MSc, RD; Phone Number: 204-631-3834; Email: kcachero@sogh.mb.ca

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R2V 3M3
      • Recruiting
      • Seven Oaks General Hospital Chronic Disease Innovation Centre
      • Principal Investigator: Dylan Mackay, PhD
      • Sub-Investigator: Rebecca Mollard, PhD
      • Contact: Navdeep Tangri, MD, PhD; Phone Number: 204-631-3834; Email: ntangri@sogh.mb.ca
      • Principal Investigator: Navdeep Tangri, MD, PhD
      • Sub-Investigator: David Collister, MD
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Not yet recruiting
      • Chronic Kidney Disease (Renal) ClinicQEII - Dickson Building
      • Contact: Karthik Tennankore, MD; Phone Number: 902-473-5543
      • Principal Investigator: Karthik Tennankore, MD
      • Sub-Investigator: Leah Cahill, MD
      • Sub-Investigator: Bohdan Lubovyy, PhD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Participant is willing and able to give informed consent for participation in the trial
• Male or Female, aged 18 years or above
• Participants who have an eGFR between 15 and 40 ml/min/1.73m2
• Two consecutive measurements of serum bicarbonate of 14 to 22 mEq/L
• Systolic and diastolic blood pressure <160/100 mmHg
• Serum potassium <5.3 mmol/L
• Hemoglobin A1c below ≤ 11%
• Are registered in the nephrology clinic in Winnipeg or Halifax
• Participants are able to communicate in English and provide written informed consent

Exclusion Criteria:

• Anuria, dialysis or acute kidney injury/acute kidney failure in the 3 months prior to screening
• Chronic obstructive pulmonary disease that requires the participant to be on oxygen
• New York Heart Association Class 3-4 Heart failure symptoms or heart, liver or renal transplant
• A myocardial infarction or stroke within the last 6 months
• Unable to consume study treatments or control, such as swallowing or GI issues
• Participants who have participated in another research trial involving an investigational product in the past 12 weeks
• Currently on potassium binding therapy
• Female participant who is pregnant or on lactating

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Alkalizing Fruit and Vegetables; Participants randomized to fruit and vegetables (F+V) will receive weekly supplementation of alkalizing fruits and vegetables via home delivery in a box format. Participants will receive a 1-hour dietary counseling session in the first week from a registered dietitian (RD), either in person or via videoconference, depending on regional coronavirus disease (COVID) 19 restrictions and participant preference, which will outline the concepts of the dietary intervention. The RD will also recommend the best ways to prepare and include the F+V into the participant's current diet. Intervention will last 12 months.	Dietary supplement: Alkalizing Fruit and Vegetables; The weekly deliveries will contain combinations of fresh, frozen, and dried fruits and vegetables, as well as juices and soups which have been selected for their negative potential renal acid load (PRAL) values and shelf-life. All participants will be started at a F+V intake equal to -30 to -40 mEq per day reduction in dietary acid load estimated by the PRAL equation. Participants serum bicarbonate concentration will be measured at 1 month, and at 3 months, those with values < 22 mEq/L will have their recommended amount of F+V increased to -40 to -50 mEq per day. If a participant's 1- or 3-month serum bicarbonate value exceeds 29 mEq/L, their target dose of F+V in mEq/d will be reduced by 25%.
Active Comparator: Sodium Bicarbonate; Participants randomized to the alkali therapy will receive oral sodium bicarbonate 500mg tablets three times a day, reflecting a common starting dose at clinical practice. Thereafter, decisions around dose titration for the sodium bicarbonate will then be transferred to the participant's nephrologist who will be responsible for monitoring the participants serum bicarbonate concentration with a goal of maintaining a serum bicarbonate level >22 mEq/L. Participants will receive counselling from a registered dietician (RD) as part of the standard care. Intervention will last 12 months.	Drug: Sodium bicarbonate; Study nephrologist will prescribe the oral alkali therapy (sodium bicarbonate) and the medications will be dispensed by the Seven Oaks Hospital pharmacy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eligibility to randomization ratio	A ratio of eligibility to randomization expressed as percentage will be collected at 12 months to investigate fruit and vegetable intervention feasibility.	12 months
Weekly recruitment rate	Number of new participants per weeks of active recruitment	12 months
Study outcome follow up	Study outcome follow up expressed as a percentage, will be calculated at 12 months to investigate the fruit and vegetable intervention feasibility	12 months
Potential renal acid load (PRAL) in mEq/day	Calculated from average dietary intake assessed by Automated Self-Administered 24-hour Canada (ASA24) dietary recall survey conducted over three days	Baseline, 6, and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Five repetition chair stand time	the amount of time it takes for a participant to get up out of a chair five times measured in seconds	Baseline, 3, 6, 9, and 12 months
Physical function related quality of life	Participants will complete the SF-12 physical component score of the Kidney Disease Quality of Life Short Form (KDQOL-SF) questionnaire. The questionnaire is scored between 0-100 with higher values representing physical function related quality of life.	Baseline, 3, 6, 9, and 12 months
Serum bicarbonate (total CO2)	Serum bicarbonate concentration in milliequivalents per liter (mEq/L)	Baseline, 1, 3, 6, 9, and 12 month(s)
Albumin	blood albumin is measured in grams per deciliter (g/dL)	Baseline, 1, 3, 6, 9, and 12 month(s)
Calcium	Total blood calcium concentration in mmol/L	Baseline, 1, 3, 6, 9, and 12 month(s)
Estimated Glomerular Filtration Rate (eGFR)	calculated from serum creatinine, sex, and age, reported in mL/min/1.73 m2	Baseline, 1, 3, 6, 9, and 12 month(s)
Glucose	Total blood glucose concentration in mmol/L	Baseline, 1, 3, 6, 9, and 12 month(s)
Potassium	The total blood potassium concentration in mmol/L	Baseline, 1, 3, 6, 9, and 12 month(s)
Chloride	Total blood chloride concentration in mmol/L	Baseline, 1, 3, 6, 9, and 12 month(s)
Sodium	The total sodium concentration in mmol/L	Baseline, 1, 3, 6, 9, and 12 month(s)
Phosphorus	The total blood phosphorus concentration in mmol/L	Baseline, 1, 3, 6, 9, and 12 month(s)
Hemoglobin A1c	Hemoglobin A1c in percentage	Baseline, 1, 3, 6, 9, and 12 month(s)
Blood Urea Nitrogen (BUN)	Blood Urea Nitrogen (BUN) is reported in millimole per litre (mmol/L)	Baseline, 1, 3, 6, 9, and 12 month(s)
Urine Albumin/Creatinine Ratio	The ratio of albumin to creatinine concentrations in urine, reported in Milligrams albumin per millimole creatinine	Baseline, 1, 3, 6, 9, and 12 month(s)
Systolic blood pressure in mmHg	Blood pressure will be measured in triplicate using a validated blood pressure monitor following Kidney Disease: Improving Global Outcomes (KDIGO) 2021 measurement guidelines, the average of the 2nd and 3rd measurements will be recorded.	Baseline, 1, 3, 6, 9, and 12 months
Diastolic blood pressure in mmHg	Blood pressure will be measured in triplicate using a validated blood pressure monitor following KDIGO 2021 measurement guidelines, the average of the 2nd and 3rd measurements will be recorded.	Baseline, 1, 3, 6, 9, and 12 months
Edmonton Symptom Assessment System (ESAS) - Revised Renal	A questionnaire used to rate the intensity of nine common symptoms experienced by renal patients, including pain, tiredness, drowsiness, nausea, appetite levels, shortness of breath, depression and anxiety levels, and well-being. Minimum value 0 and maximum value 100 with higher values being worse.	Baseline, 3, 6, 9, and 12 months
All cause hospitalization	Information on recent hospitalizations from participant's clinical records will be collected.	3, 6, 9, and 12 months
All cause mortality	Information on mortality from participant's clinical records will be collected.	3, 6, 9, 12 months
Changes in medication	Research coordinator will update information on concomitant medications or supplements information with the participant	Baseline,1, 3, 6, 9, and 12 months
Height	Height will be measured using a validated stadiometer in centimeters..	Baseline, 3, 6, 9, and 12 months
Weight	Weight will be measured using a calibrated scale in kilograms.	Baseline, 3, 6, 9, and 12 months
Body Mass Index (BMI)	MBI will be calculated through dividing weight in kilograms (kg) by the square of height in meters (m2).	Baseline, 3, 6, 9, and 12 months

Collaborators and Investigators

• Sponsor: University of Manitoba
• Collaborators: Dalhousie University; Mount Saint Vincent University
• Investigators: Principal Investigator: Navdeep Tangri, MD, PhD, Seven Oaks General Hospital Chronic Disease Innovation Centre; Principal Investigator: Dylan MacKay, PhD, George and Fay Yee Centre for Healthcare Innovation; Principal Investigator: Karthik Tennankore, MD, Nova Scotia Health Authority

Study record dates

Study Major Dates

• Study Start (Estimated): December 1, 2023
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: October 15, 2021
• First Submitted That Met QC Criteria: October 28, 2021
• First Posted (Actual): November 9, 2021

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 30, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Urologic Diseases; Disease Attributes; Renal Insufficiency; Acid-Base Imbalance; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic; Acidosis
• Other Study ID Numbers: HS24768 (B2021:025)

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