Study of Oral Uremic Toxin Absorbent/Probiotics to Modulate Systemic Inflammation and Retard the Progression of Chronic Kidney Disease in Patients With Diabetes.

Summary

Diabetes mellitus (DM) is a chronic inflammatory disease characterized by insufficient insulin secretion or insulin resistance, leading to hyperglycemia. Chronic inflammation and immune system dysfunction are characteristic of DM and can produce a plethora of cytokines and chemokines, thereby contributing to diabetic complications such as cardiovascular events and diabetic vasculopathy in DM. Besides, about 25% of people with diabetes eventually develop diabetic kidney disease (DKD). DKD is a consequence of DM with chronic kidney disease (CKD), which may abruptly increase cardiovascular disease (CVD) and its mortality rate compared with diabetes alone. Therefore, the modulation of the systemic inflammation may have the opportunity to improve both hyperglycemia and diabetic complications including vasculopathy and DKD.

Activated charcoal has been used clinically as a toxin absorbent. Some recent preclinical and clinical observations found the potential benefits and diverse effects of activated charcoal on inflammatory proteins, suggesting its potential immune modulation effects in CKD and related diseases. The current project is then designed to test the hypothesis that oral activated charcoal may be used as an anti-inflammatory strategy for diabetic complications especially DKD. We have recently demonstrated the renal protective effects of a new oral form of non-absorbable activated bamboo charcoal (ABC) in an animal model.

With OMICs studies, a growing preclinical and clinical evidence supports the theory that gut microbiome is a major contributor to adverse cardiovascular outcomes and progression of CKD, and the gut microbiota and its metabolites have the potential to be a novel therapeutic and preventative target for CKD. Additionally, current finding suggests that lncRNAs are involved in cardiovascular (CV) health and diseases. However, there is no report on the impact of gut microbiota on the host circulating lncRNA expression signature and the potential link between gut microbiota, circulating lncRNA levels changes and CKD. Although studies of probiotics which have benefits of CKD patients are numerous, few studies evaluated the effect of coadministration of activated charcoal/probiotics on the patients with CKD.

In this 12-month trial, 120 DKD subjects will be enrolled for each group (CKD group 1: CKD stage 3A; group 2: CKD stage 3B; group 3: CKD stage 4; and group 4: CKD stage 5). Each group of patients will be randomized into 6 subgroups A, B, C, D, E and F. Group A patients will receive ABC 2.3g three times a day in addition to standard care in the first 6 months, but group B patients will receive the same dosage of ABC in the last 6 months. Group C patients will receive probiotics 2g twice a day in addition to standard care in the first 6 months, but group D patients will receive the same dosage of probiotics in the last 6 months. Group E patients will receive ABC 2.3g three times a day and probiotics 2g twice a day in addition to standard care in the first 6 months, but group F patients will receive the same dosage of ABC and probiotics in the last 6 months. All patients will receive clinical assessments and examinations (gut microbiota, inflammatory proteins including CCL4, long-chain noncoding (lnc)RNAs, and uremic toxins) at baseline and every 3 months thereafter for 12 months.

Conditions

• Oral Uremic Toxin Absorbent

Interventions

DIETARY_SUPPLEMENT

oral uremic toxin absorbent

In this 12-month trial, 300 DKD participants will be enrolled (60 with CKD stage 3A, 60 with stage 3B, 60 with stage 4, and 60 with stage 5 or on dialysis). Within each stage, participants will be randomized into three subgroups (A-C). Group A will receive ABC 2.3 g three times daily together with standard care during the last 6 months. Group B will receive probiotics 2 g twice daily during the last 6 months. Group C will receive both interventions during the last 6 months. Clinical assessments and examinations- including gut microbiota, inflammatory proteins (e.g., CCL4), long non-coding RNAs (lncRNAs), and uremic toxins- will be conducted at baseline and every 3 months for 12 months.

DIETARY_SUPPLEMENT

probiotics

In this 12-month trial, 300 DKD participants will be enrolled (60 with CKD stage 3A, 60 with stage 3B, 60 with stage 4, and 60 with stage 5 or on dialysis). Within each stage, participants will be randomized into three subgroups (A-C). Group A will receive ABC 2.3 g three times daily together with standard care during the last 6 months. Group B will receive probiotics 2 g twice daily during the last 6 months. Group C will receive both interventions during the last 6 months. Clinical assessments and examinations- including gut microbiota, inflammatory proteins (e.g., CCL4), long non-coding RNAs (lncRNAs), and uremic toxins- will be conducted at baseline and every 3 months for 12 months.

DIETARY_SUPPLEMENT

oral uremic toxin absorbent + probiotics

In this 12-month trial, 300 DKD participants will be enrolled (60 with CKD stage 3A, 60 with stage 3B, 60 with stage 4, and 60 with stage 5 or on dialysis). Within each stage, participants will be randomized into three subgroups (A-C). Group A will receive ABC 2.3 g three times daily together with standard care during the last 6 months. Group B will receive probiotics 2 g twice daily during the last 6 months. Group C will receive both interventions during the last 6 months. Clinical assessments and examinations- including gut microbiota, inflammatory proteins (e.g., CCL4), long non-coding RNAs (lncRNAs), and uremic toxins- will be conducted at baseline and every 3 months for 12 months.

Sponsors & Collaborators

• National Taiwan University Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

SUPPORTIVE_CARE

Masking

SINGLE

Model

CROSSOVER

Eligibility

Min Age

20 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-12-31

Primary Completion

2029-03-31

Completion

2029-12-31

Countries

• Taiwan