Effects of Prebiotic Supplementation and Exercise on Inflammatory Markers, Vascular Function and Cognition in CKD

Study Overview
=================
Brief Summary
-----------------
The study is primarily designed to examine the effect of 16 weeks of prebiotic supplementation (resistant starch)and moderate intensity aerobic training on markers of inflammation in stage 3-4 patients with chronic kidney disease.

Detailed Description
-----------------
The primary aim of the proposed study is to determine whether the consumption of a prebiotic supplement (resistant starch) coupled with moderate intensity endurance training over 16 weeks leads to reductions in key inflammatory markers in stage 3-4 predialysis CKD patients and whether this reduction is associated with favorable changes in vascular function and indicators of stress and emotional reactivity. The investigators hypothesize that supplementation with the prebiotic (resistant starch) will lead to normalization of the microbiome of our sample of patients with chronic kidney disease (CKD) and reduce key markers of inflammation. Reductions in these biomarkers will be associated with favorable changes in cardiovascular variables along with indices of stress and emotional reactivity. Moderate intensity aerobic training will have an additive anti-inflammatory effect along with the consumption of the resistant starch.

Official Title
-----------------
Effects of Prebiotic Supplementation and Exercise on Inflammatory Markers, Vascular Function, Cognition, and Mental Well-being in Pre-Dialysis Kidney Patients

Conditions
-----------------
Chronic Kidney Diseases

Intervention / Treatment
-----------------
* Dietary Supplement: Resistant starch
* Behavioral: Exercise
* Behavioral: Starch


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: stage 3-4 of CKD (GFR 15-59 ml/min/1.73m2), ages of 30-75 years old, Must be capable of complying with and following the study protocol(diet and exercise) Must be capable of independently giving informed consent Exclusion Criteria: kidney transplant currently in a structured exercise program on antibiotic therapy within the last month On a probiotic or prebiotic supplement within the last month a GI disorder that prohibits the use of resistant starch (ie. high-amylose corn starch, which resists digestion HIV positive gastric by-pass surgery clostridium difficile marijuana user lupus rheumatoid arthritis Hepatitis C Post-traumatic stress disorder deep vein thrombosis pancreatitis

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: An Intention-To-Treat design will be used in this study. Effects of treatment on all dependent variables will be assessed by a 2 (prebiotic supplement or control) by 2 (aerobic exercise or control) by 3 (time) mixed factor ANOVA
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise<br>Exercise only: Patients randomized to this group will receive a placebo (corn starch) and be given 16 weeks of personal training. | Behavioral: Exercise<br>* Patients randomized to the exercise group will train aerobically for 16 weeks at a moderate exercise intensity<br>|
| Experimental: Resistant Starch<br>Resistant starch only: Patients randomized to this group will receive 30 g of resistant starch daily for 16 weeks. They will not be given an exercise training | Dietary Supplement: Resistant starch<br>* Patients will receive 30 grams of resistant starch daily for 16 weeks or a placebo in a double blind fashion<br>|
| Experimental: Exercise & Resistant Starch<br>Exercise & resistant starch: Patients assigned to this group will do 16 weeks of personal training and they will be supplemented with 30 g of resistant starch daily for the 16 week period | Dietary Supplement: Resistant starch<br>* Patients will receive 30 grams of resistant starch daily for 16 weeks or a placebo in a double blind fashion<br>Behavioral: Exercise<br>* Patients randomized to the exercise group will train aerobically for 16 weeks at a moderate exercise intensity<br>|
| Placebo Comparator: Starch<br>Corn starch only: Patients assigned to this group will not be given and exercise program and they will receive the placebo for 16 weeks | Behavioral: Starch<br>* Patients will be given 30 grams of corn starch<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hs CRP | hsCRP | baseline and after 16 weeks | 
| Change in TNF alpha | TNFalpha | Baseline and at week 16 | 
| Change in IL6 | IL6 | Baseline and at week 16 | 
| Change in IL10 | IL10 | Baseline and at week 16 | 
| Change in MCP1 | MCP1 | Baseline and at week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in vascular function | Pulse wave velocity | Baseline, week 8 and week 16 | 
| Change in microbiome composition | The composition of the microbiome will be assessed at baseline and after 16 weeks | Baseline and after 16 weeks | 
| Change in blood pressure | central blood pressure | Baseline & after 16 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
microbiome, inflammation, resistant starch, exercise training