Anit-Inflammatory and Anti-Oxidative Nutrition in Dialysis Patients

NCT ID: NCT00561093

Last Updated: 2015-05-21

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

93 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-02-29

Study Completion Date

2011-05-31

Brief Summary

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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

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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

Conditions

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Hypoalbuminemia Protein-energy Malnutrition Inflammation Oxidative Stress Chronic Kidney Disease (CKD) Hemodialysis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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)

Group Type EXPERIMENTAL

pentoxiphylline

Intervention Type DRUG

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

Intervention Type DIETARY_SUPPLEMENT

Nepro (8 ounces) one can while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)

anti-inflammatory module (similar to Oxepa)

Intervention Type DIETARY_SUPPLEMENT

Oxepa-similar anti-inflammatory module (2 ounces) while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)

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)

Group Type EXPERIMENTAL

Nepro

Intervention Type DIETARY_SUPPLEMENT

Nepro (8 ounces) one can while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)

anti-inflammatory module (similar to Oxepa)

Intervention Type DIETARY_SUPPLEMENT

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

Intervention Type DRUG

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)

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)

Group Type EXPERIMENTAL

pentoxiphylline

Intervention Type DRUG

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)

Placebo to imitate Nepro

Intervention Type DIETARY_SUPPLEMENT

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 anti-inflammatory module (similar to Oxepa)

Intervention Type DIETARY_SUPPLEMENT

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)

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)

Group Type PLACEBO_COMPARATOR

Placebo pill imitating pentoxiphylline

Intervention Type DRUG

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

Intervention Type DIETARY_SUPPLEMENT

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 anti-inflammatory module (similar to Oxepa)

Intervention Type DIETARY_SUPPLEMENT

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)

Interventions

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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)

Intervention Type DRUG

Nepro

Nepro (8 ounces) one can while undergoing thrice weekly hemodialysis and during the following non-dialysis day (6 days per week)

Intervention Type 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)

Intervention Type DIETARY_SUPPLEMENT

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)

Intervention Type DRUG

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)

Intervention Type 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)

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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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

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

85 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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DaVita, Inc.

INDUSTRY

Sponsor Role collaborator

Abbott Nutrition

INDUSTRY

Sponsor Role collaborator

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kamyar Kalantar-Zadeh, MD MPH PhD

Role: PRINCIPAL_INVESTIGATOR

LABioMed at Harbor-UCLA

Arezu Dezfuli, MD

Role: STUDY_DIRECTOR

LABioMed at Harbor-UCLA

Jennie Jing, MS

Role: STUDY_DIRECTOR

LABioMed at Harbor-UCLA

Locations

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DaVita Nutrition Services

Irvine, California, United States

Site Status

Los Angeles Biomedical Research Institute (LABioMed) at Harbor-UCLA

Torrance, California, United States

Site Status

Countries

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United States

References

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Kalantar-Zadeh K, Braglia A, Chow J, Kwon O, Kuwae N, Colman S, Cockram DB, Kopple JD. An anti-inflammatory and antioxidant nutritional supplement for hypoalbuminemic hemodialysis patients: a pilot/feasibility study. J Ren Nutr. 2005 Jul;15(3):318-31. doi: 10.1016/j.jrn.2005.04.004.

Reference Type BACKGROUND
PMID: 16007562 (View on PubMed)

Colman S, Bross R, Benner D, Chow J, Braglia A, Arzaghi J, Dennis J, Martinez L, Baldo DB, Agarwal V, Trundnowski T, Zitterkoph J, Martinez B, Khawar OS, Kalantar-Zadeh K. The Nutritional and Inflammatory Evaluation in Dialysis patients (NIED) study: overview of the NIED study and the role of dietitians. J Ren Nutr. 2005 Apr;15(2):231-43. doi: 10.1053/j.jrn.2005.01.003.

Reference Type BACKGROUND
PMID: 15827897 (View on PubMed)

Cooper A, Mikhail A, Lethbridge MW, Kemeny DM, Macdougall IC. Pentoxifylline improves hemoglobin levels in patients with erythropoietin-resistant anemia in renal failure. J Am Soc Nephrol. 2004 Jul;15(7):1877-82. doi: 10.1097/01.asn.0000131523.17045.56.

Reference Type BACKGROUND
PMID: 15213276 (View on PubMed)

Kalantar-Zadeh K, Kilpatrick RD, Kuwae N, McAllister CJ, Alcorn H Jr, Kopple JD, Greenland S. Revisiting mortality predictability of serum albumin in the dialysis population: time dependency, longitudinal changes and population-attributable fraction. Nephrol Dial Transplant. 2005 Sep;20(9):1880-8. doi: 10.1093/ndt/gfh941. Epub 2005 Jun 14.

Reference Type BACKGROUND
PMID: 15956056 (View on PubMed)

Kalantar-Zadeh K, Block G, McAllister CJ, Humphreys MH, Kopple JD. Appetite and inflammation, nutrition, anemia, and clinical outcome in hemodialysis patients. Am J Clin Nutr. 2004 Aug;80(2):299-307. doi: 10.1093/ajcn/80.2.299.

Reference Type BACKGROUND
PMID: 15277149 (View on PubMed)

Kalantar-Zadeh K, Ikizler TA, Block G, Avram MM, Kopple JD. Malnutrition-inflammation complex syndrome in dialysis patients: causes and consequences. Am J Kidney Dis. 2003 Nov;42(5):864-81. doi: 10.1016/j.ajkd.2003.07.016.

Reference Type BACKGROUND
PMID: 14582032 (View on PubMed)

Rammohan M, Kalantar-Zadeh K, Liang A, Ghossein C. Megestrol acetate in a moderate dose for the treatment of malnutrition-inflammation complex in maintenance dialysis patients. J Ren Nutr. 2005 Jul;15(3):345-55. doi: 10.1016/j.jrn.2004.10.006.

Reference Type BACKGROUND
PMID: 16007564 (View on PubMed)

Kalantar-Zadeh K, Balakrishnan VS. The kidney disease wasting: inflammation, oxidative stress, and diet-gene interaction. Hemodial Int. 2006 Oct;10(4):315-25. doi: 10.1111/j.1542-4758.2006.00124.x.

Reference Type BACKGROUND
PMID: 17014506 (View on PubMed)

Kalantar-Zadeh K. Recent advances in understanding the malnutrition-inflammation-cachexia syndrome in chronic kidney disease patients: What is next? Semin Dial. 2005 Sep-Oct;18(5):365-9. doi: 10.1111/j.1525-139X.2005.00074.x.

Reference Type BACKGROUND
PMID: 16191172 (View on PubMed)

Kalantar-Zadeh K, Stenvinkel P, Bross R, Khawar OS, Rammohan M, Colman S, Benner D. Kidney insufficiency and nutrient-based modulation of inflammation. Curr Opin Clin Nutr Metab Care. 2005 Jul;8(4):388-96. doi: 10.1097/01.mco.0000172578.56396.9e.

Reference Type BACKGROUND
PMID: 15930963 (View on PubMed)

Colombijn JM, Hooft L, Jun M, Webster AC, Bots ML, Verhaar MC, Vernooij RW. Antioxidants for adults with chronic kidney disease. Cochrane Database Syst Rev. 2023 Nov 2;11(11):CD008176. doi: 10.1002/14651858.CD008176.pub3.

Reference Type DERIVED
PMID: 37916745 (View on PubMed)

Mah JY, Choy SW, Roberts MA, Desai AM, Corken M, Gwini SM, McMahon LP. Oral protein-based supplements versus placebo or no treatment for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2020 May 11;5(5):CD012616. doi: 10.1002/14651858.CD012616.pub2.

Reference Type DERIVED
PMID: 32390133 (View on PubMed)

Other Identifiers

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Harbor-UCLA LABioMed # 12630

Identifier Type: -

Identifier Source: secondary_id

R21DK078012

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R21 DK78012 (completed)

Identifier Type: -

Identifier Source: org_study_id

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