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Oral Absorbent and Probiotics in CKD Patients With PAD on Gut Microbiota, IncRNA, Metabolome, and Vascular Function

Primary Purpose

CKD, PAD - Peripheral Arterial Disease

Status
Recruiting
Phase
Not Applicable
Locations
Taiwan
Study Type
Interventional
Intervention
Active bamboo charcoal
probiotics
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for CKD focused on measuring CKD, PAD - Peripheral Arterial Disease, bamboo charcoal probiotics, LncRNA, microbolomics, metabolomics, probiotics

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

I. CKD/PAD group Patients (Group I)

  1. Age > 20 years old on the day of screening.
  2. 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.
  3. Symptomatic PAD with Rutherford Stage ≥ 2 and ABI ≤ 0.9 (or documented by CT-angio, vascular duplex, etc.). II. non-CKD/PAD group Patients (Group II)

1. Age > 20 years old on the day of screening. 2.With eGFR > 60 ml/min/1.73m2 3.No clinical PAD.

Exclusion Criteria:

  1. Baseline estimated glomerular filtration rates (eGFR) < 15 ml/min/1.73m2 according to MDRD equation.
  2. Patients in severe malnutrition status, albumin less than 2.0 g/dL
  3. Patients in severe anemia or active gastrointestinal bleeding with hemoglobulin < 8 g/dL.
  4. Peptic ulcer, esophageal varices, ileus or under fasting status
  5. Previous gastrointestinal operation.
  6. 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.
  7. Patients with major hemorrhage, as defined with acute hemorrhage and requirement of blood transfusion during index admission.
  8. Patients with a biopsy proved or clinically diagnosed advanced liver cirrhosis, Child classification B or C.
  9. Solid organ or hematological transplantation recipients.
  10. Patients with oliguric kidney injury, as defined with less than 500 cc/day.
  11. Evidence of obstructive kidney injury or polycystic kidney disease.
  12. Antibiotics or probiotics treatment within the last 2 weeks before enrollment and during follow-up period.
  13. Presence or history of malignant neoplasms within the past 5 years prior to the day of screening.
  14. Patients with Acquired Immune Deficiency Syndrome.
  15. Patients with recent acute coronary syndrome, acute myocardial infarction, or severe heart failure.

Sites / Locations

  • NTUHRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

No Intervention

Arm Label

Active bamboo charcoal

Probiotics

Active bamboo charcoal+Probiotics

No invervention

Arm Description

Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The participants will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.

Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The patients will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.

Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The patients will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.

Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The patients will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.

Outcomes

Primary Outcome Measures

The change of 6-minute walking distance
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.
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.
The change of vascular duplex
Duplex ultrasound of peripheral artery
The change of serum lncRNA
Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, defined as being transcripts with lengths exceeding 200 nucleotides that are not translated into protein.

Secondary Outcome Measures

Full Information

First Posted
May 19, 2020
Last Updated
December 30, 2022
Sponsor
National Taiwan University Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT04792320
Brief Title
Oral Absorbent and Probiotics in CKD Patients With PAD on Gut Microbiota, IncRNA, Metabolome, and Vascular Function
Official Title
Therapeutic Impact of Oral Uremic Toxin Absorbent and Probiotics in Chronic Kidney Disease Patients With Peripheral Arterial Disease--- on Gut Microbiota, Circulating Long Noncoding RNA, Metabolome, and Vascular Function
Study Type
Interventional

2. Study Status

Record Verification Date
September 2022
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2020 (Actual)
Primary Completion Date
May 31, 2023 (Anticipated)
Study Completion Date
May 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Taiwan has more chronic kidney disease (CKD) per capita than anywhere in the world, leading to the highest expense of National Health Insurance. By reviewing previous studies, uremic toxins contribute critically to the detrimental effects of CKD on atherosclerotic peripheral artery disease (PAD). When recognized early and managed appropriately, mortality and complications of the participants with CKD and established PAD can be minimized. It is critical to identify novel biomarkers and mediators, which can help identify those with potential poor outcomes and facilitate the discovery/development of novel therapeutics for the patients with CKD and PAD. The OMICs studies support the theory that gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD. However, successful integration of multi-omics approach remains sparse. There is no report on the impact of gut microbiota on the host circulating long non-coding RNAs (lncRNAs) expression signature, other CAD/PAD potential marker, and the potential link between gut microbiota, circulating lncRNA levels changes and CKD/PAD. Additionally, although numerous studies indicated that probiotics or activated charcoal have benefits for CKD patients, few studies evaluated the effect of coadministration of activated charcoal/probiotics on the patients with CKD/PAD. The mechanisms of therapeutic effect on CKD/PAD patients with coadministration of activated charcoal/probiotics involving the cross talk among host, microbiota and metabolites still remain unclear. Thus, in the present study, investigators aim to develop novel diagnostic/prognostic markers and a new treatment with activated bamboo charcoal (ABC)/probiotics for therapeutic opportunities to prevent cardiovascular complications, amputation and death in CKD patients with established PAD. To identify the diagnostic/prognostic markers, the multi-omics (microbolome and metabolome) and lncRNA will be analyzed. The therapeutic impact of activated bamboo charcoal (ABC)/probiotics with optimal formulation, on the renal/endothelial/vascular function, cardiovascular (CV) outcome and mortality in CKD patients with PAD will be also determined to evaluate its therapeutic opportunities.
Detailed Description
Taiwan has more chronic kidney disease (CKD) per capita than anywhere in the world, leading to the highest expense of National Health Insurance. By reviewing previous studies, uremic toxins contribute critically to the detrimental effects of CKD on atherosclerotic peripheral artery disease (PAD). When recognized early and managed appropriately, mortality and complications of the participants with CKD and established PAD can be minimized. It is critical to identify novel biomarkers and mediators, which can help identify those with potential poor outcomes and facilitate the discovery/development of novel therapeutics for the participants with CKD and PAD. The OMICs studies support the theory that gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD. However, successful integration of multi-omics approach remains sparse. There is no report on the impact of gut microbiota on the host circulating long non-coding RNAs (lncRNAs) expression signature, other CAD/PAD potential marker, and the potential link between gut microbiota, circulating lncRNA levels changes and CKD/PAD. Additionally, although numerous studies indicated that probiotics or activated charcoal have benefits for CKD patients, few studies evaluated the effect of coadministration of activated charcoal/probiotics on the participants with CKD/PAD. The mechanisms of therapeutic effect on CKD/PAD patients with coadministration of activated charcoal/probiotics involving the cross talk among host, microbiota and metabolites still remain unclear. Thus, in the present study, investigators aim to develop novel diagnostic/prognostic markers and a new treatment with activated bamboo charcoal (ABC)/probiotics for therapeutic opportunities to prevent cardiovascular complications, amputation and death in CKD patients with established PAD. To identify the diagnostic/prognostic markers, the multi-omics (microbolome and metabolome) and lncRNA will be analyzed. The therapeutic impact of activated bamboo charcoal (ABC)/probiotics with optimal formulation, on the renal/endothelial/vascular function, cardiovascular (CV) outcome and mortality in CKD patients with PAD will be also determined to evaluate its therapeutic opportunities. Additionally, the possible mechanisms including the molecular pathway and the roles of microbiota associated with expression profiles of lncRNA and metabolome linked to adverse CV/limb outcome will be investigation. Through combination of innovative molecular biological techniques with new approaches for clinical research, investigators will develop a novel therapy by updated knowledge of the mechanisms of disease and by improved pharmacological technology for the CKD patients with established PAD. Investigators expect to demonstrate the clinical efficacy of ABC ± probiotics to improve symptoms and outcomes of CKD patients with PAD, and offer a possibility to develop a precision medicine with novel diagnostic/prognostic markers and special ABC/probiotic formula, which will ultimately lead to the improved clinical care and outcomes in this population.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CKD, PAD - Peripheral Arterial Disease
Keywords
CKD, PAD - Peripheral Arterial Disease, bamboo charcoal probiotics, LncRNA, microbolomics, metabolomics, probiotics

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
180 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active bamboo charcoal
Arm Type
Experimental
Arm Description
Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The participants will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.
Arm Title
Probiotics
Arm Type
Experimental
Arm Description
Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The patients will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.
Arm Title
Active bamboo charcoal+Probiotics
Arm Type
Experimental
Arm Description
Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The patients will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.
Arm Title
No invervention
Arm Type
No Intervention
Arm Description
Eligible 120 participants (group I),The other 60 eligible controls (group II) will be also randomized into ABC-treatment (A) or no-treatment (B) with a 1:1 ratio. The patients will receive CharXenPlus 4g particles ( containing ABC 2g) thrice daily for 6 months in subgroups IA and IIA. While the patients in subgroups IB and IIB will not receive any ABC. The subgroups IA and IB will be further randomly subdivided into IAa, IAb, IBa, and IBb subsubgroups. All the patients will receive probiotics APL-MIX2 (CharXprob) 0.8 g powder once a day in the last 3 months except those in subsubgroups IAb and IBb.
Intervention Type
Dietary Supplement
Intervention Name(s)
Active bamboo charcoal
Other Intervention Name(s)
CharXenPlus
Intervention Description
4g particle
Intervention Type
Dietary Supplement
Intervention Name(s)
probiotics
Other Intervention Name(s)
Charxprob
Intervention Description
0.8g powder
Primary Outcome Measure Information:
Title
The change of 6-minute walking distance
Description
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
baseline, 3rd month, 6th month, 1st year, 2nd year and 3rd year
Title
The change of ABI
Description
The ABI value is determined by taking the higher pressure of the 2 arteries at the ankle, divided by the brachial arterial systolic pressure.
Time Frame
baseline, 3rd month, 6th month, 1st year, 2nd year and 3rd year
Title
The change of vascular duplex
Description
Duplex ultrasound of peripheral artery
Time Frame
baseline, 3rd month, 6th month, 1st year, 2nd year and 3rd year
Title
The change of serum lncRNA
Description
Long non-coding RNAs (long ncRNAs, lncRNA) are a type of RNA, defined as being transcripts with lengths exceeding 200 nucleotides that are not translated into protein.
Time Frame
baseline, 3rd month, 6th month, 1st year, 2nd year and 3rd year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: I. CKD/PAD group Patients (Group I) 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. non-CKD/PAD group Patients (Group II) 1. Age > 20 years old on the day of screening. 2.With eGFR > 60 ml/min/1.73m2 3.No clinical PAD. Exclusion Criteria: 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. Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Patients with Acquired Immune Deficiency Syndrome. Patients with recent acute coronary syndrome, acute myocardial infarction, or severe heart failure.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chau chung Wu
Phone
02-23123456
Ext
88560
Email
Chauchungwu@ntu.edu.tw
First Name & Middle Initial & Last Name or Official Title & Degree
Mei-Chang Huang
Phone
02-23123456
Ext
88559
Email
r204.cc01@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chau chung Wu
Organizational Affiliation
National Taiwan University Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
NTUH
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chau chung Wu, PhD
Phone
02-23123456
Ext
88560
Email
Chauchungwu@ntu.edu.tw
First Name & Middle Initial & Last Name & Degree
Mei-Chen Huang, master
Phone
02-23123456
Ext
885589
Email
r204.cc01@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Oral Absorbent and Probiotics in CKD Patients With PAD on Gut Microbiota, IncRNA, Metabolome, and Vascular Function

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