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

NCT04788914 | Recruiting

• 1 other identifier: 201907105MINC
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

CKD; PAD

Keywords

Bamboo charcoal; LncRNA; gut microbiota; CKD; PAD; Probiotics

Outcome Measures

Primary Outcomes (2)

• 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.

  baseline, 3th month and 6th month

• The change of ABI

  The ABI value is determined by taking the higher pressure of the 2 arteries at the ankle, divided by the brachial arterial systolic pressure.

  baseline, 3th month and 6th month

Secondary Outcomes (5)

• The change of InCRNA

  baseline, 3th month and 6th month

• The change of microbiota

  baseline, 3th month and 6th month

• The change of EPC

  baseline, 3th month and 6th month

• The change of eGFR

  baseline, 3th month and 6th month

• The change of UACR

  baseline, 3th month and 6th month

Study Arms (2)

Active bamboo charcoal

OTHER

In this proposal, 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, 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. 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.

Dietary Supplement: Active bamboo charcoal± probiotics

Probiotics

OTHER

The therapeutic impact of probiotics on 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.

Dietary Supplement: Active bamboo charcoal± probiotics

Interventions

Active bamboo charcoal± probiotics DIETARY_SUPPLEMENT

Active bamboo charcoal 2g, TID probiotics 0.8g

Active bamboo charcoal; Probiotics

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• I: Patients
• 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.).
• II: Controls
• Age \> 20 years old on the day of screening.
• With eGFR \> 60 ml/min/1.73m2
• No clinical PAD.

You may not qualify if:

• 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
• Previous gastrointestinal operation.
• Chronic constipation, as defined with less than 3 bowel movements per week, straining, hard stools, incomplete evacuation and inability to pass stool. If usage of oral laxatives can achieve bowel movement, this patient will not be excluded.
• Patients with major hemorrhage, as defined with acute hemorrhage and requirement of blood transfusion during index admission.
• Patients with a biopsy proved or clinically diagnosed advanced liver cirrhosis, Child classification B or C.
• Solid organ or hematological transplantation recipients.
• Patients with oliguric kidney injury, as defined with less than 500 cc/day.
• Evidence of obstructive kidney injury or polycystic kidney disease.
• Antibiotics or probiotics treatment within the last 2 weeks before enrollment and during follow-up period.

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

NTUH

Taipei, Taiwan, Taiwan

RECRUITING

Study Officials

• Chau chung Wu

  National Taiwan University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chau chung Wu

CONTACT

02-23123456; Chauchungwu@ntu.edu.tw

Mei-Chang Huang

CONTACT

02-23123456; r204.cc01@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2020
• First Posted: March 9, 2021
• Study Start: April 21, 2020
• Primary Completion: December 30, 2024
• Study Completion: July 31, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)