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CompletedNCT04600323Updated Dec 20, 2024Results posted

Bicarbonate Administration and Cognitive Function in Midlife and Older Adults With CKD

An Early Phase 1 interventional study of Sodium Bicarbonate Tablets and Placebo in Metabolic Acidosis, Chronic Kidney Disease and Cognitive Dysfunction, sponsored by University of Colorado, Denver. Completed at 1 site in United States. Open to participants aged 50 Years to 70 Years. Per ClinicalTrials.gov, last updated 2024-12-20.

Sponsored by University of Colorado, Denver · Early Phase 1, Interventional, and Treatment

Phase
Early Phase 1
Study type
Interventional
Enrollment
34
Allocation
Randomized
Ages
50 Years to 70 Years
Sex
All
01

Study summary

This is a pilot, randomized, double-blinded, placebo-controlled, 12-month trial of 50 patients with CKD stage 3b-4 with metabolic acidosis to examine the effect of sodium bicarbonate therapy on cognitive and cerebrovascular function.

02

Conditions studied

  • Metabolic Acidosis
  • Chronic Kidney Disease
  • Cognitive Dysfunction
03

In context

Kidney Diseases

3,840 studies on the registry are indexed under Kidney Diseases; 500 are open to participants now.

This study's enrollment of 34 is below the median of 70 across 2,640 interventional studies indexed under Kidney Diseases.

Browse Kidney Diseases studies →

Lead sponsor

University of Colorado, Denver is the lead sponsor of 1,499 studies on the registry; 315 are open to participants now.

Of its 139 completed or terminated interventional studies of FDA-regulated products, 89 (64%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 70 Years
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • Age 50-75 years old
  • Serum bicarbonate 16-22 mEq/L on 2 separate measurements (at least 1 day apart)
  • CKD stage 3b or 4 at time of screening (eGFR 15-44 ml/min/1.73m2)
  • Blood pressure \<130/80 mm Hg prior to randomization
  • Use of angiotensin converting enzyme inhibitor or angiotensin receptor blocker
  • Stable anti-hypertensive regimen for at least one month prior to randomization
  • Montreal Cognitive Assessment Score > 24
  • No history of stroke
  • No history of dementia
  • No history of neurologic disease
  • Able to provide consent

Exclusion Criteria:• Significant comorbid conditions that lead the investigator to conclude that life expectancy is less than 1 year

  • Use of chronic daily oral alkali within the last 3 months (including sodium bicarbonate, calcium carbonate or baking soda)
  • Uncontrolled hypertension
  • Serum potassium \< 3.3 or ≥ 5.5 mEq/L at screening
  • New York Heart Association Class 3 or 4 heart failure symptoms, known EF ≤30%, or hospital admission for heart failure within the past 3 months
  • Factors judged to limit adherence to interventions
  • Anticipated initiation of dialysis or kidney transplantation within 12 months
  • Current participation in another research study
  • Pregnancy or planning to become pregnant or currently breastfeeding
  • Chronic use of supplemental oxygen
05

Study design

Phase
Early Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
34 participants (actual)

Study arms

  • Placebo comparator
    Placebo

    Placebo medication will be used at a dose of 0.5 mEq/kg-lean body weight/day

    Drug: Placebo

  • Experimental
    Sodium bicarbonate

    Sodium bicarbonate will be used at a dose of 0.5 mEq/kg-lean body weight/day.

    Drug: Sodium Bicarbonate Tablets

Interventions

  • DrugSodium Bicarbonate Tablets

    Participants will be given sodium bicarbonate at 0.5 mEq/kg-LBW/day for 12 months

  • DrugPlacebo

    Participants will be given placebo at 0.5 mEq/kg-LBW/day for 12 months

06

What researchers measure

Primary outcomes

  1. Change in Cognitive Function Composite Score at 12 Months

    Cognitive function will be determined using the NIH Toolbox-Cognition Battery computerized tests. The Cognitive function composite score is based on the average of the Fluid and Crystallized composites. It is derived by averaging the Fluid and Crystallized standard scores, then deriving standard scores based on this new distribution. Fully Corrected T-scores are adjusted for for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance.

    Time frame: Baseline and 12 months

  2. Change in Fluid Cognition Composite Score at 12 Months

    NIH Toolbox will be used to assess fluid cognition composite score. This score includes all the tests that are measuring fluid ability: Flanker, Dimensional Change, Picture sequence memory, list sorting and pattern comparison. The composite score is derived by averaging the standard scores of each of the measures. Fully Corrected T-scores are adjusted for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. A fully corrected T-score at or near 50 (population mean with standard deviation of 10) indicates ability that is average compared with others nationally and one below 40 suggests the possibility of cognitive impairment. N

    Time frame: baseline and 12 months

  3. Change in Crystallized Cognition Composite Score at 12 Months

    NIH Toolbox will be used to assess crystallized cognition composite score. This composite score includes the picture vocabulary and reading tests. The composite score is derived by averaging the standard scores of each of the measure, and then driving standard scores based on this new distribution. Fully Corrected T-scores are adjusted for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. A fully corrected T-score at or near 50 (population mean with standard deviation of 10) indicates ability that is average compared with others nationally as the mean T-score is 50 nationally. A score higher than 50 indicates better crystallized cognition.

    Time frame: baseline and 12 months

Secondary outcomes

  1. Change in Cerebrovascular Reactivity at 12 Months

    Relative cerebrovascular reactivity was calculated as % change in mean blood flow velocity of the middle cerebral artery/(hypercapnia breath-by-breath end-tidal partial pressure of CO2 (ETCO2) minus resting ETCO2).

    Time frame: Baseline and 12 months

  2. Percent Change in Mean Blood Flow Velocity of the Middle Cerebral Artery at 12 Months

    Measured using Transcranial Doppler Ultrasonography in response to a vasodilatory hypercapnic challenge.The change in mean blood flow velocity of the middle cerebral artery (MVMCA) was computed as the difference between hypercapnic MVMCA and normocapnic MVMCA

    Time frame: Baseline and 12 months

07

Results

Posted Dec 20, 2024

Participant flow

Participant flow — Overall Study
MilestonePlaceboSodium Bicarbonate
Started1618
Completed1617
Not completed01

Outcome measures

PrimaryChange in Cognitive Function Composite Score at 12 Months

Cognitive function will be determined using the NIH Toolbox-Cognition Battery computerized tests. The Cognitive function composite score is based on the average of the Fluid and Crystallized composites. It is derived by averaging the Fluid and Crystallized standard scores, then deriving standard scores based on this new distribution. Fully Corrected T-scores are adjusted for for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. The T-score has a mean of 50 in the general population and a SD of 10. Scores higher than the mean indicate better performance.

Time frame:
Baseline and 12 months
Reported as:
Mean · T-score
Change in Cognitive Function Composite Score at 12 Months
T-scorePlaceboSodium Bicarbonate
Baseline52.3 ± 8.847.3 ± 8.5
12 months53.5 ± 8.549.3 ± 11.0
PrimaryChange in Fluid Cognition Composite Score at 12 Months

NIH Toolbox will be used to assess fluid cognition composite score. This score includes all the tests that are measuring fluid ability: Flanker, Dimensional Change, Picture sequence memory, list sorting and pattern comparison. The composite score is derived by averaging the standard scores of each of the measures. Fully Corrected T-scores are adjusted for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. A fully corrected T-score at or near 50 (population mean with standard deviation of 10) indicates ability that is average compared with others nationally and one below 40 suggests the possibility of cognitive impairment. N

Time frame:
baseline and 12 months
Reported as:
Mean · T-score
Change in Fluid Cognition Composite Score at 12 Months
T-scorePlaceboSodium Bicarbonate
Baseline52.1 ± 10.844.7 ± 8.7
12 months53.0 ± 9.446.9 ± 11.7
PrimaryChange in Crystallized Cognition Composite Score at 12 Months

NIH Toolbox will be used to assess crystallized cognition composite score. This composite score includes the picture vocabulary and reading tests. The composite score is derived by averaging the standard scores of each of the measure, and then driving standard scores based on this new distribution. Fully Corrected T-scores are adjusted for age, gender, race/ethnicity, and educational attainment. The score compares the score of the participant to those in the NIH Toolbox nationally representative normative sampling. A fully corrected T-score at or near 50 (population mean with standard deviation of 10) indicates ability that is average compared with others nationally as the mean T-score is 50 nationally. A score higher than 50 indicates better crystallized cognition.

Time frame:
baseline and 12 months
Reported as:
Mean · T-score
Change in Crystallized Cognition Composite Score at 12 Months
T-scorePlaceboSodium Bicarbonate
Baseline52.8 ± 8.349.6 ± 8.0
12 months53.5 ± 7.650.6 ± 9.0
SecondaryChange in Cerebrovascular Reactivity at 12 Months

Relative cerebrovascular reactivity was calculated as % change in mean blood flow velocity of the middle cerebral artery/(hypercapnia breath-by-breath end-tidal partial pressure of CO2 (ETCO2) minus resting ETCO2).

Time frame:
Baseline and 12 months
Reported as:
Mean · percent change/mmHg
Change in Cerebrovascular Reactivity at 12 Months
percent change/mmHgPlaceboSodium Bicarbonate
Baseline2.5 ± 1.42.4 ± 1.2
12 months2.7 ± 1.32.5 ± 1.1
SecondaryPercent Change in Mean Blood Flow Velocity of the Middle Cerebral Artery at 12 Months

Measured using Transcranial Doppler Ultrasonography in response to a vasodilatory hypercapnic challenge.The change in mean blood flow velocity of the middle cerebral artery (MVMCA) was computed as the difference between hypercapnic MVMCA and normocapnic MVMCA

Time frame:
Baseline and 12 months
Reported as:
Mean · percent change
Percent Change in Mean Blood Flow Velocity of the Middle Cerebral Artery at 12 Months
percent changePlaceboSodium Bicarbonate
Baseline26.2 ± 17.022.6 ± 13.1
12 months32.3 ± 21.725.0 ± 12.4

Adverse events

Collected over 12 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Placebo0/16 (0%)7/16 (43.8%)6/16 (37.5%)
Sodium Bicarbonate0/18 (0%)6/18 (33.3%)13/18 (72.2%)
Most frequent serious events
Most frequent serious events
EventPlaceboSodium Bicarbonate
HospitalizationInfections and infestations5/163/18
HospitalizationCardiac disorders2/163/18
Most frequent other events
Most frequent other events
EventPlaceboSodium Bicarbonate
Increase in antihypertensive therapyCardiac disorders4/164/18
New Lower Extremity EdemaCardiac disorders2/163/18
Increase in diuretic therapyCardiac disorders0/163/18
Dialysis initiationRenal and urinary disorders0/162/18
High serum bicarbonate levelRenal and urinary disorders0/161/18

Baseline characteristics

Age, Continuous
Age, Continuous(years)PlaceboSodium BicarbonateTotal
Mean60.6 ± 5.962.0 ± 7.561.3 ± 6.8
Sex: Female, Male
Sex: Female, Male(Participants)PlaceboSodium BicarbonateTotal
Female6511
Male101323
Race (NIH/OMB)
Race (NIH/OMB)(Participants)PlaceboSodium BicarbonateTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American022
White161632
More than one race000
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)PlaceboSodium BicarbonateTotal
United States161834
Hypertension
Hypertension(Participants)PlaceboSodium BicarbonateTotal
Count of participants161632
Diabetes
Diabetes(Participants)PlaceboSodium BicarbonateTotal
Count of participants101222
Bicarbonate (mEq/L)
Bicarbonate (mEq/L)(mEq/L)PlaceboSodium BicarbonateTotal
Mean21.8 ± 1.923.0 ± 1.522.7 ± 2.3
GFR (ml/min/1.73m2)
GFR (ml/min/1.73m2)(ml/min/1.73m2)PlaceboSodium BicarbonateTotal
Mean32.8 ± 10.936.9 ± 16.734.8 ± 13.9
08

Study locations

1 site
  • University of Colorado Anschutz Medical Campus
    Aurora, Colorado 80045, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · May 3, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes

Supporting information: Study protocol, Sap, Csr, Analytic code

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Dec 20, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT04600323
Lead sponsor
University of Colorado, Denver
Responsible party
Sponsor
First posted
Oct 23, 2020
Start date
Feb 1, 2021
Primary completion
Aug 30, 2023
Completion
Aug 30, 2023
Results posted
Dec 20, 2024
Last update
Dec 20, 2024

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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