Anit-Inflammatory and Anti-Oxidative Nutrition in Dialysis Patients
Condition: Hypoalbuminemia; Protein-energy Malnutrition; Inflammation; Oxidative Stress; Chronic Kidney Disease (CKD) Hemodialysis
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Hypoalbuminemia; Malnutrition; Protein-Energy Malnutrition; Inflammation
Study type: Interventional
Phase: Phase 3

Summary: 
      Study of efficiency and safety of oral nutritional supplements with anti-inflammatory and
      antioxidative properties combined with an appetite stimulant with anti-inflammatory
      properties (pentoxiphylline) in treatment of malnutrition-inflammation-cachexia syndrome in
      maintenance hemodialysis patients
    

Detailed description: 
      There are 350,000 hemodialysis patients in the USA; these are people who have end-stage kiney
      disease and whose survival depends on thrice weekly hemodialysis treatment in a dialysis
      clinic. Hemodialysis patients have an unacceptably high death rate, so that one out of every
      4 to 5 patients die each year. Almost half of all deaths are believed to be from heart
      disease. Because markers of malnutrition and inflammation such as low amount of blood protein
      (serum albumin <4.0 g/dL), rather than traditional risk factors, are among the strongest
      predictors of early death and because malnutrition-inflammation appears to be closely related
      to oxidative stress in hemodialysis patients, we would like to examine that hypotesis that
      treating malnutrition-inflammation-oxidation by mean of nutritional support may improve
      outcomes in them. Low serum albumin <4.0 g/dL is observed in almost half of all hemodialysis
      patients and appears associated with low appetite, wasting, inflammation, malfunction of the
      vessels, cardiovascular disease and several fold increase in mortality.

      We hypothesize that the malnutrition-inflammation can be significantly corrected by a simple
      in-center oral nutritional support with anti-inflammatory and antioxidant properties combined
      with an appetite stimulant with anti-inflammatory properties, leading to improved clinical
      and nutritional outcome measures in hemodialysis patients. We have proposed to the National
      Institutes of Health a pilot/feasibility study where dialysis patients will have 50-50 chance
      of receiving real treatment or a fake version of it (placebo). This method is called
      randomization, and this study type is called "randomized placebo-controlled clinical trial"
      with two arms, a so-called 2x2 factorial design. Our proposed study has a low-priced but
      efficient operational system and will be performed in 8 to 10 DaVita dialysis clinics in Los
      Angles area. During this 2-year pilot/feasibility study, we will test whether our proposed
      nutritional and anti-inflammatory treatments are safe and can improve low serum albumin and
      other relevant outcomes in 100 hemodialysis patients. Subjects will be adult hemodialysis
      patients with a serum albumin <4.0 g/dL.

      The nutritional support arm will include a combination of 2 oral nutritional supplements;
      i.e., Nepro™ (8 oz), tailored for malnourished hemodialysis patients; and a condensed
      anti-inflammatory module similar to Oxepa™ (2 oz), designed for sick patients with
      inflammation and oxidative stress; or their placebos. The appetite stimulating arm will
      include a medication known as "pentoxifylline" (also known as Trental™) and the dose will be
      400 mg daily or its placebo.

      If a patient qualifies and agrees to participate in the study, there will be one month of
      observations and tests, followed by 16 weeks of treatment, and then one additional month of
      observation at the end. Both interventions are administered thrice weekly during routine
      hemodialysis for 16 weeks. Nutritional, inflammatory and oxidative measures, vessel wall
      (endothelial) function, quality of life and other clinical measures will be obtained before,
      during, and after the intervention. The safety and tolerability of the treatments, the
      feasibility of the study design, and the measurability of the outcomes will be examined.

      We hope that the successful completion of this pilot/feasibility study in our campus leads to
      design of a large-scale clinical trial at the national level to improve survival in dialysis
      patients using nutritional and anti-inflammatory treatments.

      Figure 1. Proposed pilot/feasibility study (see Appendix 1 for color version)

      Group A (n=25) Nepro/Oxepa (2 cans) + PTX (400 mg) while on HD & the following day

      Group B (n=25) Nepro/Oxepa (2 CANS) + placebo PTX while on HD& the following day

      Group C (n=25) Placebo 2 cans + PTX (400 mg) while on HD& the following day

      Group D (n=25) Placebo 2 cans + placebo PTX while on HD& the following day

      PTX: pentoxifylline HD: Hemodialysis
    

Intervention name(s): pentoxiphylline; Nepro; anti-inflammatory module (similar to Oxepa); Placebo pill imitating pentoxiphylline; Placebo to imitate Nepro; Placebo to imitate anti-inflammatory module (similar to Oxepa)
Intervention type(s): Drug; Dietary Supplement; Dietary Supplement; Drug; Dietary Supplement; Dietary Supplement
Intervention description(s): pentoxiphylline 400 mg daily, anti-inflammatory and appetite-stimulating while subjects undergo thrice weekly hemodialysis and during the following non-dialysis day (6 days per week); Nepro (8 ounces) one can while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week); Oxepa-similar anti-inflammatory module (2 ounces) while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week); Placebo pill imitating pentoxiphylline 400 mg daily, to imitate the anti-inflammatory and appetite-stimulating pill while subjects undergo thrice weekly hemodialysis and during the following non-dialysis day (6 days per week); Placebo to imitate Nepro (8 ounces), with less protein and calorie, one can while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week); Placebo to imitate Oxepa-similar anti-inflammatory module (2 ounces), without anti-inflammatory or anti-oxidative ingredients, while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)
Other intervention name(s): Trental, 400 mg pills; Nepro with Carb ™ Steady; Oxepa-similar anti-inflammatory module (2 ounces); Placebo pill imitating pentoxiphylline 400 mg daily, to imitate the anti-; inflammatory and appetite-stimulating pill while subjects undergo thrice; weekly hemodialysis and during the following non-dialysis day (6 days per week); Placebo to imitate Nepro (8 ounces), with less protein and calorie,; Placebo to immitate Oxepa-similar anti-inflammatory module (2 ounces), without anti-inflammatory or anti-oxidative ingredients,; 0011084880
Intervention MeSH terms: Anti-Inflammatory Agents; Pentoxifylline
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hypoalbuminemia; Protein-energy malnutrition; Inflammation; Oxidative stress; Chronic Kidney disease (CKD) stage 5; maintenance hemodialysis