Trial Outcomes & Findings for Evaluation of Coffee Therapy for Improvement of Renal Oxygenation (NCT NCT03878277)

Results Overview

Measured by blood oxygen level dependent (BOLD MRI), before and after Lasix injection;Regions of interest (ROI) analysis for BOLD MRI will be performed on a Leonardo Workstation (Siemens Medical Systems, Germany). Typically, 1 to 3 regions in each, cortex and medulla, per kidney per slice will be defined leading to a total of about 10 ROIs per region (cortex and medulla) per subject. The mean and standard deviation of these 10 measurements will be used a R2\* measurement for the region, for the subject and for that time point. Additionally, two (delta) R2\*s will be calculated as defined below: (delta) R2\*(medulla, furosemide) = R2\* (medulla, pre-furosemide) - R2\* (medulla, post-furosemide); (delta) R2\*(cortex, medulla) = Baseline R2\* (medulla) - Baseline R2\* (cortex).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

1 hour

Results posted on

2022-02-15

Participant Flow

Participant milestones

Participant milestones
Measure	Cold Brew Coffee 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Overall Study STARTED	10
Overall Study COMPLETED	10
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Evaluation of Coffee Therapy for Improvement of Renal Oxygenation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cold Brew Coffee n=10 Participants 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Age, Continuous	18.5 years STANDARD_DEVIATION 2.6 • n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants
Race/Ethnicity, Customized White non-Hispanic	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: 1 hour

Measured by blood oxygen level dependent (BOLD MRI), before and after Lasix injection;Regions of interest (ROI) analysis for BOLD MRI will be performed on a Leonardo Workstation (Siemens Medical Systems, Germany). Typically, 1 to 3 regions in each, cortex and medulla, per kidney per slice will be defined leading to a total of about 10 ROIs per region (cortex and medulla) per subject. The mean and standard deviation of these 10 measurements will be used a R2\* measurement for the region, for the subject and for that time point. Additionally, two (delta) R2\*s will be calculated as defined below: (delta) R2\*(medulla, furosemide) = R2\* (medulla, pre-furosemide) - R2\* (medulla, post-furosemide); (delta) R2\*(cortex, medulla) = Baseline R2\* (medulla) - Baseline R2\* (cortex).

Outcome measures

Outcome measures
Measure	Cold Brew Coffee n=10 Participants 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Renal Oxygenation Before cold brew	22.4 s^-1 Standard Deviation 1.5
Renal Oxygenation After cold brew	22.5 s^-1 Standard Deviation 2.1

PRIMARY outcome

Timeframe: 1 hour

Measured by pseudocontinuous arterial spin labeling (pCASL) MRI; ROI analysis will be used to estimate (delta) M (difference in signal intensity between non-selective and selective inversion images). Using the same ROI, M0 will be estimated from the proton density image. T1 measurements from the same ROI will be obtained by fitting the signal intensity vs. inversion time data as described previously (104) using XLFit (ID Business Solutions Ltd., UK) or T1 maps created using MRI Mapper (Beth Israel Deaconess Medical Center, Boston). Partition coefficient will be assumed to be 0.8 ml/gm (105, 106). These values will then be used to estimate regional blood flow.

Outcome measures

Outcome measures
Measure	Cold Brew Coffee n=10 Participants 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Renal Perfusion After cold brew (Left kidney ASL)	3.03 ml/s/100g Standard Deviation 0.72
Renal Perfusion Before cold brew (Right kidney ASL)	3.02 ml/s/100g Standard Deviation 0.67
Renal Perfusion After cold brew (Right kidney ASL)	3.03 ml/s/100g Standard Deviation 0.62
Renal Perfusion Before cold brew (Left kidney ASL)	3.15 ml/s/100g Standard Deviation 0.50

SECONDARY outcome

Timeframe: 4 hours

Measured by Iohexol clearance; An intravenous (IV) line was placed, and participants were asked to empty their bladders. Spot plasma and urine samples were collected prior to iohexol infusion. Iohexol was administered through bolus IV injection (5 mL of 300 mg/mL; Omnipaque 300, GE Healthcare). An equilibration period of 120 min was used and blood collections for iohexol plasma disappearance were drawn at +120, +150, +180, +210, +240 min (11). Because the Brøchner-Mortensen equation underestimates high values of GFR, the Jødal-Brøchner-Mortensen equation was used to calculate the GFR (12). We report absolute GFR (mL/min) and RPF (mL/min) in the main analyses because the practice of indexing GFR and RPF for body surface underestimates hyperfiltration and hyperperfusion (14), and body surface area (BSA) calculations introduce noise into the clearance measurements.

Outcome measures

Outcome measures
Measure	Cold Brew Coffee n=10 Participants 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Glomerular Filtration Rate Before cold brew	3.25 ml/s Standard Deviation 0.47
Glomerular Filtration Rate After cold brew	3.27 ml/s Standard Deviation 0.80

SECONDARY outcome

Timeframe: 4 hours

Measured by para-aminohippurate (PAH) clearance; An intravenous (IV) line was placed, and participants were asked to empty their bladders. Spot plasma and urine samples were collected prior PAH infusion. PAH (2 g/10 mL, prepared at the University of Minnesota, with a dose of \[weight in kg\]/75 × 4.2 mL; IND #140129) was given slowly over 5 min followed by a continuous infusion of 8 mL of PAH and 42 mL of normal saline at a rate of 24 mL/h for 2 h. After an equilibration period, blood was drawn at 90 and 120 min, and RPF was calculated as PAH clearance divided by the estimated extraction ratio of PAH, which varies by the level of GFR (13). We report absolute GFR (mL/min) and RPF (mL/min) in the main analyses because the practice of indexing GFR and RPF for body surface underestimates hyperfiltration and hyperperfusion (14), and body surface area (BSA) calculations introduce noise into the clearance measurements.

Outcome measures

Outcome measures
Measure	Cold Brew Coffee n=10 Participants 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Effective Renal Plasma Flow Before cold brew	13.08 ml/s Standard Deviation 1.58
Effective Renal Plasma Flow After cold brew	13.02 ml/s Standard Deviation 0.67

SECONDARY outcome

Timeframe: 4 hours

Measured by markers of kidney injury in plasma; Cystatin C (mg/L) was measured by immunoturbidimetric method (Kamiya Biomedical) by our Clinical Translational Research Center Core Laboratory.

Outcome measures

Outcome measures
Measure	Cold Brew Coffee n=10 Participants 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Tubular Injury Markers Before cold brew (cystatin C)	0.82 mg/L Standard Deviation 0.18
Tubular Injury Markers After cold brew (cystatin C)	0.84 mg/L Standard Deviation 0.19

Adverse Events

Cold Brew Coffee

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Cold Brew Coffee n=10 participants at risk 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am. Starbucks® Cold brew - 325ml bottle: Starbucks® Cold brew 325ml bottles daily \[205mg caffeine\] will be provided to the participants. Participants will be instructed to drink 1 bottle every morning between 6 and 9 am for 6 days prior to the post-intervention visit. The 7th day is the post-intervention visit, and participants will be asked to drink 1 bottle the morning of the study visit
Vascular disorders Vasovagal syncope	10.0% 1/10 • During the duration of trial with cold brew (7 days) as well as 24 hours after the last study visit.

Additional Information

Petter Bjornstad, M.D., Assistant Professor of Pediatrics and Medicine

University of Colorado School of Medicine

Phone: 7207774659

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place