Type1diabetesPhase 2COFFEENCT03878277
Evaluation of Coffee Therapy for Improvement of Renal Oxygenation
A Phase 2 study testing Starbucks® Cold brew - 325ml bottle in people with Type1diabetes and Type1 Diabetes Mellitus, run by University of Colorado, Denver at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 12 to 21 years
- Conditions the study is for
- Type1diabetes, Type1 Diabetes Mellitus, Diabetic Kidney Disease
- What is being tested?
- Starbucks® Cold brew - 325ml bottle
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2019to 30 Sep 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Youth with T1D (antibody +) with <10 year duration
- Age 12-21 years
- Weight >57 lbs and <350 lbs
- BMI >5th %ile
- HbA1c <12%
- Previous exposure to caffeine
Who cannot join
- Anemia
- Allergy to shellfish or iodine
- Severe illness, recent diabetic ketoacidosis (DKA)
- Tachyarrhythmias, Attention-deficit/hyperactivity disorder (ADHD), tremors, tics, Tourette's, arrythmias, insomnia, overactive bladder
- Estimated Glomerular Filtration Rate (eGFR) <60 ml/min/1.73 m2 or creatinine > 1.5 mg/dl or history of albumin-to-creatinine ratio (ACR) >300 mg/g
- MRI Scanning contraindications (claustrophobia, implantable metal devices that are non-MRI compatible, >350 lbs)
- Pregnancy or nursing
- (Angiotensin-converting enzyme) ACE inhibitors, angiotensin receptor blockers (ARBs), diuretics, sodium-glucose co-transport (SGLT) 2 or 1 blockers, daily NSAIDs or aspirin, sulfonamides, thiazolsulfone or probenecid, atypical antipsychotics, steroids
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital Colorado
Aurora, Colorado, 80045
About this study
Official title: Coffee, Renal Oxygenation, Blood Flow and Glomerular Filtration Rate in Early Diabetic Kidney Disease.
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).
- Conditions
- Type1diabetes, Type1 Diabetes Mellitus, Diabetic Kidney Disease, Juvenile Diabetes, Diabetic Nephropathies, Diabetes Complications
- Being tested
- Starbucks® Cold brew - 325ml bottle
- Medical subject headings
- Diabetic Nephropathies, Diabetes Mellitus, Type 1, Diabetes Complications
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Starbucks® Cold brew - 325ml bottleDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Cold Brew Coffee | Experimental | 6 days of drinking 1 bottle of Starbucks® Cold brew 325ml [205 mg caffeine] every morning between 6am-9am. Receives: Drug: Starbucks® Cold brew - 325ml bottle |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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.
Measured: 1 hour
Secondary outcomes (3)
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.
Measured: 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.
Measured: 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.
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2019
- Study start1 Jul 2019
- Primary completion21 Jan 2020
- Study completion30 Sep 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Type1diabetesStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Collaborators
- Johns Hopkins University
- Responsible party
- Sponsor
- Investigators
- Petter Bjornstad, MD, Principal investigator, University of Colorado Denver | Anschutz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03878277
- Sponsor's protocol ID
- 18-1874
- Acronym
- COFFEE
- Status last verified
- Jan 2022
- First submitted
- 14 Mar 2019
- Last updated
- 15 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No