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| Name | Class |
|---|---|
| Johns Hopkins University | OTHER |
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Over 1.25 million Americans have Type 1 Diabetes (T1D), increasing risk for early death from cardiovascular disease (CVD). Despite advances in glycemic and blood pressure control, a child diagnosed with T1D is expected to live up to 17 years less than non-diabetic peers. The strongest risk factor for CVD and mortality in T1D is diabetic kidney disease (DKD). Current treatments, such as control of hyperglycemia and hypertension, are beneficial, but only partially protect against DKD. This limited progress may relate to a narrow focus on clinical manifestations of disease, rather than on the initial metabolic derangements underlying the initiation of DKD. Renal hypoxia, stemming from a potential metabolic mismatch between increased renal energy expenditure and impaired substrate utilization, is increasingly proposed as a unifying early pathway in the development of DKD. T1D is impacted by several mechanisms which increase renal adenosine triphosphate (ATP) consumption and decrease ATP generation.
Caffeine, a methylxanthine, is known to alter kidney function by several mechanisms including natriuresis, hemodynamics and renin-angiotensin-aldosterone system. In contrast, to other natriuretic agents, caffeine is thought to fully inhibit the local tubuloglomerular feedback (TGF) response to increased distal sodium delivery. This observation has broad-ranging implications as caffeine can reduce renal oxygen (O2) consumption without impairing effective renal plasma flow (ERPF) and glomerular filtration rate (GFR).
There are also data suggesting that chemicals in coffee besides caffeine may provide important cardio-renal protection. Yet, there are no data examining the impact of coffee-induced natriuresis on intrarenal hemodynamic function and renal energetics in youth-onset T1D. Our overarching hypothesis in the proposed pilot and feasibility trial is that coffee drinking improves renal oxygenation by reducing renal O2 consumption without impairing GFR and ERPF. To address these hypotheses, we will measure GFR, ERPF, renal perfusion and oxygenation in response to 7 days of cold brew coffee (one Starbucks® Cold brew 325ml bottle daily [205mg caffeine]) in an open-label pilot and feasibility trial in 10 adolescents with T1D already enrolled in the CASPER Study (PI: Bjornstad).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cold Brew Coffee | Experimental | 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml [205 mg caffeine] every morning between 6am-9am. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Starbucks® Cold brew - 325ml bottle | Drug | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Renal Oxygenation | 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). | 1 hour |
| Renal Perfusion | 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. | 1 hour |
| Measure | Description | Time Frame |
|---|---|---|
| Glomerular Filtration Rate | 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Petter Bjornstad, MD | University of Colorado Denver | Anschutz | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Hospital Colorado | Aurora | Colorado | 80045 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Renal Oxygenation | 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). | Posted | Mean | Standard Deviation | s^-1 | 1 hour |
|
During the duration of trial with cold brew (7 days) as well as 24 hours after the last study visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Vasovagal syncope | Vascular disorders | Non-systematic Assessment | Participant reported experiencing dizziness and lightheadedness during manipulation of peripheral IV by nursing staff during the hyperglycemic clamp. Participant given option to leave or continue in study. Participant chose to finish the study visit. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Petter Bjornstad, M.D., Assistant Professor of Pediatrics and Medicine | University of Colorado School of Medicine | 7207774659 | petter.bjornstad@childrenscolorado.org |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 3, 2019 | Aug 5, 2021 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003928 | Diabetic Nephropathies |
| D003922 | Diabetes Mellitus, Type 1 |
| D048909 | Diabetes Complications |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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|
| 4 hours |
| Effective Renal Plasma Flow | 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. | 4 hours |
| Tubular Injury Markers | 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. | 4 hours |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
|
|
| Primary | Renal Perfusion | 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. | Posted | Mean | Standard Deviation | ml/s/100g | 1 hour |
|
|
|
| Secondary | Glomerular Filtration Rate | 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. | Posted | Mean | Standard Deviation | ml/s | 4 hours |
|
|
|
| Secondary | Effective Renal Plasma Flow | 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. | Posted | Mean | Standard Deviation | ml/s | 4 hours |
|
|
|
| Secondary | Tubular Injury Markers | 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. | Posted | Mean | Standard Deviation | mg/L | 4 hours |
|
|
|
| 0 |
| 10 |
| 0 |
| 10 |
| 1 |
| 10 |
|
Not provided
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| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
|
| After cold brew (Left kidney ASL) |
|