lncRNAs as a Biomarker to Assess the Therapeutic Impact of Oral Absorbent ± Probiotics in CKD Patients With PAD

ConditionsCKD PAD

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age20+

SponsorNational Taiwan University Hospital

About this trial

Participants with chronic kidney disease (CKD) are at a higher risk of developing atherosclerotic peripheral artery disease (PAD). Retention of uremic toxins such as indoxyl sulfate (IS), p-cresyl sulfate (PCS) and trimethylamine N-oxide (TMAO) during CKD is detrimental to endothelial and vascular function and can predispose to the development and progression of PAD. Many of the uremic toxins originate from gut microbial metabolism. Removal of these uremic toxins by carbonaceous oral adsorbent is beneficial, slowing down the deterioration of renal function and delaying the need for dialysis in CKD patients. However, if carbonaceous oral adsorbent could also improve vascular function and clinical outcomes in CKD patients with established PAD, remains unknown.

In this proposal, the investigators aim to determine the therapeutic impact of a carbonaceous oral adsorbent made of activated bamboo charcoal (ABC) with/without probiotics on the endothelial/vascular function, CV outcome and mortality in CKD patients with PAD. In addition, the investigators hypothesize that circulating long noncoding RNA (lncRNA) expression profiles and metabolome may serve as a sensitive and reliable biomarker to predict the adverse CV outcomes and death in CKD patients with established PAD. In addition, it is hypothesized that circulating lncRNAs and linked to adverse CV outcomes in CKD patients with PAD are associated with dysbiosis of gut microbiota. The investigators also hypothesize that the administration of ABC could normalize the dysbiosis of gut microbiota, dysregulated circulating lncRNAs and metabolome that are linked to adverse CV/limb outcomes in CKD patients with PAD.

This will be a prospective, randomized, open-labeled, blinded end-point trial for 6 months, followed by integrated assessment of endothelial/vascular function, changes in conventional athero- and inflammation-relevant biomarkers, circulating long noncoding RNAs, metabolome, and gut microbiota at baseline, ends of the 3rd and 6th month, as well as clinical CV, renal and limb outcomes up to 3 years.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age > 20 years old on the day of screening.

CKD patients with eGFR 15 < eGFR < 60 ml/min/1.73m2 in a stable status, creatinine elevated less than 0.3 mg/dL in at least 30 days before enrollment.

Symptomatic PAD with Rutherford Stage ≥ 2 and ABI < 0.9 (or documented by CT-angio, vascular duplex, etc.).

Age > 20 years old on the day of screening.

Disqualifiers

Baseline estimated glomerular filtration rates (eGFR) < 15 ml/min/1.73m2 according to MDRD equation.

Patients in severe malnutrition status, albumin less than 2.0 g/dL

Patients in severe anemia or active gastrointestinal bleeding with hemoglobulin < 8 g/dL.

Peptic ulcer, esophageal varices, ileus or under fasting status

Trial design

Design model

Parallel

Treatments tested in this trial

Active bamboo charcoal± probiotics
Dietary supplement
Active bamboo charcoal 2g, TID probiotics 0.8g

Treatment groups

180 Participants

are divided into 2 treatment groups

Group A: Active bamboo charcoalOther 1 intervention

Group B: ProbioticsOther 1 intervention

Trial outcomes

Primary outcomes

The change of the six-minute walk test

The 6 Minute Walk Test is a sub-maximal exercise test used to assess aerobic capacity and endurance. The distance covered over a time of 6 minutes is used as the outcome by which to compare changes in performance capacity.

Time frame