Official Title: “Pilot/Feasibility Randomized Control Trial to Examine the Effect of Oral Nutritional Supplements With Anti-Inflammatory/Anti-Oxidative Properties and Pentoxiphylline on Malnutrition-Inflammation-Cachexia Syndrome in Maintenance Hemodialysis Patients”

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

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Factorial Assignment, Safety/Efficacy Study

Study Primary Completion Date: January 2010

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(s) in this Clinical Trial

• Drug: pentoxiphylline
  • 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)
• Dietary Supplement: Nepro
  • Nepro (8 ounces) one can while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)
• Dietary Supplement: anti-inflammatory module (similar to Oxepa)
  • Oxepa-similar anti-inflammatory module (2 ounces) while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)
• Drug: Placebo pill imitating pentoxiphylline
  • 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)
• Dietary Supplement: Placebo to imitate Nepro
  • 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)
• Dietary Supplement: Placebo to imitate anti-inflammatory module (similar to Oxepa)
  • 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)

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • Group A (n=25) Nepro (8 ounces) and Oxepa-similar anti-inflammatory module (2 ounces) AND pentoxiphylline (400 mg) while undergoing hemodialysis and the following non-dialysis day (6 days per week)
• Experimental: B
  • Group B (n=25) Nepro (8 ounces) and Oxepa-similar anti-inflammatory module (2 ounces) AND Placebo to imitate pentoxiphylline while undergoing hemodialysis and the following non-dialysis day (6 days per week)
• Experimental: C
  • Group C (n=25) Placebo dietary supplement to imitate Nepro (8 ounces) and Oxepa-similar anti-inflammatory module (2 ounces) AND pentoxiphylline (400 mg) while undergoing hemodialysis and the following non-dialysis day (6 days per week)
• Placebo Comparator: D
  • Group D (n=25) Placebo to imitate Nepro (8 ounces) and Oxepa-similar anti-inflammatory module (2 ounces) AND Placebo to imitate pentoxiphylline (400 mg) while undergoing hemodialysis and the following non-dialysis day (6 days per week)

Primary Measures

• Change in serum albumin
  • Time Frame: 16 weeks
    Safety Issue?: No

Secondary Measures

• Changes in body composition and measures of nutrition, inflammation, anemia, Health related quality of life (HRQOL), and tolerance
  • Time Frame: 16 weeks
    Safety Issue?: Yes

Inclusion Criteria:

• At least 3 months on maintenance hemodialysis,
• Last 3-month averaged serum albumin <4.0 g/dl,
• Average monthly Kt/V>1.2,
• Dialysis time between 3 and 5 hours,
• Functioning AV graft or fistula or tunnel catheter that will not switch for 6 months,
• Standardized dialysis treatment per DaVita protocol.
• In case the averaged 3-month is not <4.0 g/dl but last month serum albumin <4.0 g/dl (worsening hypoalbuminemia) patient will be qualified, if 3-month averaged nPNA < 0.8 g/kg/day or a BMI < 20 kg/m2.

Exclusion Criteria:

• Peritoneal dialysis
• Terminal illnesses with life expectancy<6 months
• Maintenance hemodialysis less than 5 months
• Concurrent appetite stimulants
• Use of IDPN in the past 2-3 months
• Inability to follow and to comply with the instructions and guidelines
• Likelihood of pregnancy or intention to become pregnant
• Acute wasting condition or active systemic disease
• Pulse chemo therapy
• Non-compliance with dialysis treatment
• Dialysis catheter that may switch soon.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 85 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Overall Clinical Trial Officials and Contacts

Kamyar Kalantar-Zadeh, MD MPH PhD Principal Investigator LABioMed at Harbor-UCLA  

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00561093

Study ID Number: DK78012

ClinicalTrials.gov Identifier: NCT00561093

Health Authority: United States: Institutional Review Board

NIED (Nutrition & Inflammation Evaluation in Dialysis Patients) Study