Study of Oral Uremic Toxin Absorbent/Probiotics to Modulate Systemic Inflammation and Retard the Progression of Chronic Kidney Disease in Patients With Diabetes.
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About
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.
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Inclusion criteria
- Age > 20 years old but not pregnant on the day of screening.
- DKD patients with stable renal function (Cre elevation < 0.3 mg/dL for at least 30 days) and PCS level (fluctuation < 10% for at least 30 days)
- Group 1: 120 DKD patients with 45<eGFR<60 ml/min/1.73m2 in stable status. Group 2: 120 DKD patients with 30<eGFR<45 ml/min/1.73m2 in stable status. Group 3: 60 DKD patients with 15<eGFR<30 ml/min/1.73m2 in stable status Group 4: 60 DKD patients with eGFR<15 ml/min/1.73m2 in stable status
Exclusion criteria
- Baseline eGFR > 90 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.
- Active 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.
- Evidence of obstructive kidney injury or polycystic kidney disease.
- Presence or history of malignant neoplasms within the past 5 years prior to the day of screening.
- Patients with Immune Deficiency Syndrome.
- Antibiotics or probiotics treatment within the last 3 months before enrollment and during follow-up period.
Trial design
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Interventional model
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300 participants in 3 patient groups
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Central trial contact
chauchung wu, PhD
Data sourced from clinicaltrials.gov
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