Evaluation of Coffee Therapy for Improvement of Renal Oxygenation
Condition: Type1diabetes; Type1 Diabetes Mellitus; Diabetic Kidney Disease; Juvenile Diabetes; Diabetic Nephropathies; Diabetes Complications; Diabetes, Autoimmune
MeSH terms: Kidney Diseases; Diabetic Nephropathies; Diabetes Mellitus; Diabetes Mellitus, Type 1; Diabetes Complications
Intervention: Starbucks® Cold brew - 325ml bottle
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 12 Years
Maximum age: 21 Years
Healthy volunteers: No

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. 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).
    

Eligibility criteria:

        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