Evaluation of Coffee Therapy for Improvement of Renal Oxygenation

NCT03878277 | Completed Phase 2 Results FDA Drug

• 1 other identifier: 18-1874
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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).

Conditions

Type1diabetes; Type1 Diabetes Mellitus; Diabetic Kidney Disease; Juvenile Diabetes; Diabetic Nephropathies; Diabetes Complications; Diabetes, Autoimmune

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (3)

• Glomerular Filtration Rate

  4 hours

• Effective Renal Plasma Flow

  4 hours

• Tubular Injury Markers

  4 hours

Study Arms (1)

Cold Brew Coffee

EXPERIMENTAL

6 days of drinking 1 bottle of Starbucks® Cold brew 325ml \[205 mg caffeine\] every morning between 6am-9am.

Drug: Starbucks® Cold brew - 325ml bottle

Interventions

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

Cold Brew Coffee

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Johns Hopkins University: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Diabetic Nephropathies; Diabetes Mellitus, Type 1; Diabetes Complications

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Mellitus; Endocrine System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Petter Bjornstad, M.D., Assistant Professor of Pediatrics and Medicine
• Organization: University of Colorado School of Medicine

petter.bjornstad@childrenscolorado.org

7207774659

Study Officials

• Petter Bjornstad, MD

  University of Colorado Denver | Anschutz

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2019
• First Posted: March 18, 2019
• Study Start: July 1, 2019
• Primary Completion: January 21, 2020
• Study Completion: September 30, 2021
• Last Updated: February 15, 2022
• Results First Posted: August 31, 2021

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)