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

  • STATUS
    Recruiting
  • End date
    May 31, 2025
  • participants needed
    180
  • sponsor
    National Taiwan University Hospital
Updated on 15 March 2021

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.

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 ml/min/1.73m2 and symptomatic PAD will be screened for eligibility. The other healthy adults will be enrolled as control.

Participants who fulfill the inclusion/exclusion 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 0.5mg/dL and kidney biopsy approved Glomerulonephritis.

Eligible 120 participants (group I) with eGFR 15 < eGFR < 60 ml/min/1.73m2 and symptomatic PAD will be randomized into ABC-treatment (A) or no-treatment (B)participants with a 1:1 ratio. The other 60 eligible controls (eGFR > 60 ml/min/1.73m2 and no PAD, 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 (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) 0.8 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.

Details
Condition peripheral arterial disease, Peripheral Arterial Disease (PAD), Peripheral Arterial Disease (PAD), CKD, chronic kidney disease, peripheral arterial diseases, peripheral artery disease, chronic kidney disease (ckd)
Treatment Active bamboo charcoal± probiotics
Clinical Study IdentifierNCT04788914
SponsorNational Taiwan University Hospital
Last Modified on15 March 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

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

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note