Ignite Creation Date:
2024-05-06 @ 3:52 PM
Last Modification Date:
2024-10-26 @ 1:59 PM
Study NCT ID:
NCT04788914
Status:
RECRUITING
Last Update Posted:
2023-01-03
First Post:
2020-05-19
Brief Title:
lncRNAs as a Biomarker to Assess the Therapeutic Impact of Oral Absorbent Probiotics in CKD Patients With PAD
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Circulating Long Noncoding RNA as a Biomarker to Assess the Therapeutic Impact of Oral Uremic Toxin Absorbent Probiotics in Chronic Kidney Disease Patients With Peripheral Arterial Disease
Status:
RECRUITING
Status Verified Date:
2022-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 withwithout probiotics on the endothelialvascular 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 CVlimb 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 endothelialvascular 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
In this proposal the investigators aim to determine the therapeutic impact of a carbonaceous oral adsorbent made of activated bamboo charcoal ABC withwithout probiotics on the endothelialvascular 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 CVlimb 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 endothelialvascular 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
Detailed Description:
This is a prospective randomized open-labeled blinded end-point so called PROBE trial for 6 months All patients presented to the clinics of participating sites with advanced CKD with eGFR 15 eGFR 60 mlmin173m2 and symptomatic PAD will be screened for eligibility The other healthy adults will be enrolled as control
Participants who fulfill the inclusionexclusion criteria will be invited to participate in the current study After the participants provides the written informed consents detailed demographic data including genders ages body weights body heights smoking status never past or active the baseline creatinine the nadir value in the past three months and its corresponding eGFR and CKD stages degrees of albuminuria Urine albumin creatinine ratio UACR NYHA functional class presence of atrial fibrillation prior cardiovascular disease CVD including myocardial infarct peripheral arterial occlusive diseases presence of diabetes mellitus DM or hypertension Detailed medication list will also be obtained with the focus on angiotensin receptor blocker or angiotensin converting enzyme inhibitors statins and beta-blockers
The etiology of kidney injury will be non-mutual-exclusively categorized as
1 Hypertensive kidney disease participants who received any kind of anti-hypertensive drugs
2 Diabetic kidney disease patients who received any kind of anti-diabetics drugs
3 Glomerulonephritis patients who have proteinuria more than 05mgdL and kidney biopsy approved Glomerulonephritis
Eligible 120 participants group I with eGFR 15 eGFR 60 mlmin173m2 and symptomatic PAD will be randomized into ABC-treatment A or no-treatment Bparticipants with a 11 ratio The other 60 eligible controls eGFR 60 mlmin173m2 and no PAD group II will be also randomized into ABC-treatment A or no-treatment B with a 11 ratio The participants will receive CharXenPlus 4g with ABC 2g thrice daily for 6 months in subgroups IA and IIA while the participants 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 participants will receive probiotics APL-MIX2 CharXprob 08 g once a day in the last 3 months except those in subsubgroups IAb and IBb
After being processed urine stool and plasma samples will be stored in -80C for further examinations The names and chart numbers participants will be masked to provide adequate privacy The coding book connecting codes and individual participants will be filed separately in order to protect participants privacy participants will be asked if investigators can keep the encrypted samples refrigerated for 10 years for further investigations
Participants who fulfill the inclusionexclusion criteria will be invited to participate in the current study After the participants provides the written informed consents detailed demographic data including genders ages body weights body heights smoking status never past or active the baseline creatinine the nadir value in the past three months and its corresponding eGFR and CKD stages degrees of albuminuria Urine albumin creatinine ratio UACR NYHA functional class presence of atrial fibrillation prior cardiovascular disease CVD including myocardial infarct peripheral arterial occlusive diseases presence of diabetes mellitus DM or hypertension Detailed medication list will also be obtained with the focus on angiotensin receptor blocker or angiotensin converting enzyme inhibitors statins and beta-blockers
The etiology of kidney injury will be non-mutual-exclusively categorized as
1 Hypertensive kidney disease participants who received any kind of anti-hypertensive drugs
2 Diabetic kidney disease patients who received any kind of anti-diabetics drugs
3 Glomerulonephritis patients who have proteinuria more than 05mgdL and kidney biopsy approved Glomerulonephritis
Eligible 120 participants group I with eGFR 15 eGFR 60 mlmin173m2 and symptomatic PAD will be randomized into ABC-treatment A or no-treatment Bparticipants with a 11 ratio The other 60 eligible controls eGFR 60 mlmin173m2 and no PAD group II will be also randomized into ABC-treatment A or no-treatment B with a 11 ratio The participants will receive CharXenPlus 4g with ABC 2g thrice daily for 6 months in subgroups IA and IIA while the participants 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 participants will receive probiotics APL-MIX2 CharXprob 08 g once a day in the last 3 months except those in subsubgroups IAb and IBb
After being processed urine stool and plasma samples will be stored in -80C for further examinations The names and chart numbers participants will be masked to provide adequate privacy The coding book connecting codes and individual participants will be filed separately in order to protect participants privacy participants will be asked if investigators can keep the encrypted samples refrigerated for 10 years for further investigations
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None