Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04819217 |
| Other study ID # |
202002030RINA |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2020 |
| Est. completion date |
May 31, 2025 |
Study information
| Verified date |
May 2020 |
| Source |
National Taiwan University Hospital |
| Contact |
Chau chung Wu, Ph.D. |
| Phone |
02-23123456 |
| Email |
Chauchungwu[@]ntu.edu.tw |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
In patients with chronic kidney disease (CKD), uremic toxins accumulate when kidney function
declines. Those uremic toxins had a greater affinity to circulating proteins are called
"protein bound uremic toxins, PBUT." Apart from traditional small or middle molecule uremic
toxins, the PBUTs can be rarely eliminated using traditional renal replacement therapy, even
using high flux dialysis modalities. Among these molecules identified, indoxyl sulfate (IS),
and p-cresol (PC) are mostly studied. Both in vitro and in vivo study, IS and PC are
associated with endothelial dysfunction, vascular smooth muscle proliferation, and increased
risk for CV outcomes.
The uremic toxins (IS and PC) are originated in the endogenous environment, mainly from the
protein metabolism, food intake, or produced by gut microbiota. Prevention of IS or PC
precursors from being absorbed across the intestinal tract has been extensively studied in
the renal literature by use of oral adsorbents. In animal models, activated charcoal reduces
the serum concentration of creatinine (cre) and may delay CKD progression by alleviating IS
overload. An oral form of non-absorbable surface-modified activated bamboo charcoal (ABC),
has been demonstrated to effectively reduce circulating and renal IS levels in animal models.
Recently, probiotics, prebiotics or synbiotics have been reported to reduce inflammation,
improve kidney function and retard progression of CKD by restoring the symbiosis of gut
microflora in patients with CKD. A randomized trial found synbiotics decreased serum PCS
without reducing serum IS in non-dialysis CKD. Another study found that synbiotics delayed
CKD progression. A systematic review found prebiotic and probiotic therapies reduced IS and
PCS in patients with end stage kidney disease (ESKD) on haemodialysis. However, it is unclear
whether the results hold true for other patients with CKD. Based on these previous findings,
investigators will conduct a prospective randomized open blinded end-point (PROBE) study to
see if oral uremic toxin absorbent + probiotics prevent CKD progression. Also, a panel of
clinical and biochemical profiles will be checked to investigate possible link between
several biomarkers and clinical response.
Description:
In patients with chronic kidney disease (CKD), uremic toxins accumulate when kidney function
declines. Those uremic toxins had a greater affinity to circulating proteins are called
"protein bound uremic toxins, PBUT." Apart from traditional small or middle molecule uremic
toxins, the PBUTs can be rarely eliminated using traditional renal replacement therapy, even
using high flux dialysis modalities. Among these molecules identified, indoxyl sulfate (IS),
and p-cresol (PC) are mostly studied. Both in vitro and in vivo study, IS and PC are
associated with endothelial dysfunction, vascular smooth muscle proliferation, and increased
risk for CV outcomes.
The uremic toxins (IS and PC) are originated in the endogenous environment, mainly from the
protein metabolism, food intake, or produced by gut microbiota. Prevention of IS or PC
precursors from being absorbed across the intestinal tract has been extensively studied in
the renal literature by use of oral adsorbents. In animal models, activated charcoal reduces
the serum concentration of creatinine (cre) and may delay CKD progression by alleviating IS
overload. An oral form of non-absorbable surface-modified activated bamboo charcoal (ABC),
has been demonstrated to effectively reduce circulating and renal IS levels in animal models.
Recently, probiotics, prebiotics or synbiotics have been reported to reduce inflammation,
improve kidney function and retard progression of CKD by restoring the symbiosis of gut
microflora in patients with CKD. A randomized trial found synbiotics decreased serum PCS
without reducing serum IS in non-dialysis CKD. Another study found that synbiotics delayed
CKD progression. A systematic review found prebiotic and probiotic therapies reduced IS and
PCS in patients with end stage kidney disease (ESKD) on haemodialysis. However, it is unclear
whether the results hold true for other patients with CKD. Based on these previous findings,
investigators will conduct a prospective randomized open blinded end-point (PROBE) study to
see if oral uremic toxin absorbent + probiotics prevent CKD progression. Also, a panel of
clinical and biochemical profiles will be checked to investigate possible link between
several biomarkers and clinical response.
During this 6 months' trial, eligible 120 patients with eGFR 15 < eGFR < 45 ml/min/1.73m2 and
UACR > 100 mg/g will be enrolled and randomized into 4 groups. The patients in group 1 will
receive CharXenPlus 4g (with ABC 2g) thrice daily + CharXprob 0.8 g once daily in the initial
3 months. Group 2 will receive CharXenPlus 4g thrice daily in the initial 3 months, and
CharXprob 0.8 g once daily in the last 3 months. Group 3 will receive CharXprob 0.8 g once
daily in the initial 3 months, and CharXenPlus 4g thrice daily in the last 3 months. Group 4
will only receive CharXprob 0.8 g once daily in the last 3 months. In addition to demographic
data, the degrees of proteinuria (UACR), serum albumin, AST, ALT, BUN, creatinine, Na, K, Cl,
Ca, P, Mg, uric acid, IS, PC, TMAO, FGF-23, klotho, KIM-1, NGAL, metabolomics, lcnRNA, and
fecal microbiota will be assessed at the baseline, 3rd and 6th month of the trial.
