Evaluation of Coffee Therapy for Improvement of Renal Oxygenation (COFFEE)

University of Colorado Denver (CU Denver)

Status and phase

Completed

Phase 2

Conditions

Diabetic Nephropathies

Diabetes Complications

Type1 Diabetes Mellitus

Juvenile Diabetes

Type1diabetes

Diabetes, Autoimmune

Diabetic Kidney Disease

Treatments

Drug: Starbucks® Cold brew - 325ml bottle

Study type

Interventional

Funder types

Other

Identifiers

NCT03878277

18-1874

Details and patient eligibility

About

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).

Enrollment

10 patients

Sex

All

Ages

12 to 21 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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

Exclusion criteria

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