Effects of High Dietary Fiber Supplementation in Diabetic Chronic Kidney Disease

Sponsor

University of Utah (Other)

Overall Status

Completed

CT.gov ID

NCT01838330

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Loss of kidney function results in accumulation in the blood of molecules that are either excreted or metabolized by the kidney. Collectively, these molecules are termed Uremic Retention Molecules (URMs) or toxins. It is increasingly recognized that colonic bacterial metabolites like p-cresyl sulfate and indoxyl sulfate that are absorbed from the colon and excreted by the kidney may contribute to the pool of compounds implied in uremic toxicity. Indeed, these URMs have been linked to increased levels of inflammation markers, chronic kidney disease (CKD) progression, cardiovascular disease and overall mortality in CKD and/ or hemodialysis patients. Therefore, interventions that target the production or absorption of URMs from the gut might decrease inflammation and oxidative stress that are commonly seen in the uremic milieu. The National Health and Nutrition Examination Survey III (NHANES III) data show that high dietary fiber intake is associated with decreased serum levels of C-reactive protein (CRP) in those with and without CKD and these associations are much stronger in the CKD population. A possible explanation of this effect is that a high fiber diet in CKD patients modulates the bacterial production, intestinal absorption and finally the serum levels of URMs like p-cresyl sulfate and indoxyl sulfate, which in turn results in decrease in inflammation.

OBJECTIVES:

Hypothesis:

Higher serum levels of markers of inflammation such as high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6) and tumor necrosis factor (TNF) -α seen in stage 4 CKD (estimated Glomerular Filtration Rate 15-29 ml/min/1.73 m2) compared to stage 2 CKD (estimated Glomerular Filtration Rate 60-89 ml/min/1.73 m2) is partly explained by the higher circulating levels of URMs (p-cresyl sulfate and indoxyl sulfate) in stage 4 CKD, and
Dietary supplementation in stage 4 CKD with 30g/d of a soluble fiber Psyllium (brand name-Metamucil TM) will decrease circulating URMs levels and thereby, decrease serum levels of inflammation markers and urinary levels of transforming growth factor (TGF)-β, a marker of kidney fibrosis.

Condition or Disease	Intervention/Treatment	Phase
Kidney Disease	Dietary Supplement: psyllium	N/A

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Effects of High Dietary Fiber Supplementation on Uremic Retention Molecules and Inflammation in Diabetic Chronic Kidney Disease (CKD)

Study Start Date :

Jun 1, 2012

Actual Primary Completion Date :

Jan 1, 2016

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chronic Kidney Disease Stage 3-4 Study participants with stage 3 or 4 CKD will receive 15 grams/day of soluble fiber psyllium for the first week, followed by 30 grams/day of a soluble fiber psyllium for 4 months.	Dietary Supplement: psyllium 15 grams/day for 1 week, followed by 30 grams/day for 4 months Other Names: Metamucil
No Intervention: Chronic Kidney Disease Stage 1-2 Study participants with stage 1 or 2 CKD will not receive study treatment

Arm

Intervention/Treatment

Experimental: Chronic Kidney Disease Stage 3-4

Study participants with stage 3 or 4 CKD will receive 15 grams/day of soluble fiber psyllium for the first week, followed by 30 grams/day of a soluble fiber psyllium for 4 months.

Dietary Supplement: psyllium

15 grams/day for 1 week, followed by 30 grams/day for 4 months

Other Names:

Metamucil

No Intervention: Chronic Kidney Disease Stage 1-2

Study participants with stage 1 or 2 CKD will not receive study treatment

Outcome Measures

Primary Outcome Measures

p-cresyl sulfate serum concentration [4 months]
Comparison of serum p-cresyl sulfate concentration between Stage 3-4 CKD subjects (following treatment with soluble fiber psyllium) and Stage 1-2 CKD subjects (having received no study treatment)

Secondary Outcome Measures

Indoxyl sulfate serum concentration [4 months]
Comparison of serum indoxyl sulfate concentration between Stage 3-4 CKD subjects (following treatment with soluble fiber psyllium) and Stage 1-2 CKD subjects (having received no study treatment)
Interleukin-6 (IL-6) serum concentration [4 months]
Comparison of serum IL-6 concentration between Stage 3-4 CKD subjects (following treatment with soluble fiber psyllium) and Stage 1-2 CKD subjects (having received no study treatment)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with or without diabetes and Stage 1 or 2 CKD (estimated Glomerular Filtration Rate > 60 mL/min/1.73 m2) with urine dipstick positive for protein or urinary albumin/ creatinine > 30 mg/g of creatinine; or
Stage 3 or 4 CKD (estimated Glomerular Filtration Rate < 60 to 15 mL/min/1.73 m2).