Enteral Nutrition in Congestive Heart Failure and Cardiac Cachexia

Chronic Heart Failure Clinical Trial

Official title:

The Influence of Enteral Nutrition on Functional Status and Inflammatory Activation in Patients With Congestive Heart Failure and Cardiac Cachexia.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00654719
• Other study ID #: 372/2000
• Status: Completed
• Phase: Phase 2
• First received: April 3, 2008
• Last updated: April 3, 2008
• Start date: April 2001
• Est. completion date: February 2002

Study information

• Verified date: April 2008
• Source: National Heart and Lung Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Poland: National Monitoring Centre for Clinical Trials - Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The purpose of this study was to determine the effects of a high caloric drink on weight and several other clinical markers including quality of life in patients with unintentional weight loss (cachexia) due to chronic heart failure.

Description:

Cardiac cachexia has been shown to be powerful independent predictor of mortality in patients with congestive heart failure (CHF). Unlike starvation, cachectic CHF patients present with a decrease of muscles and/or fat tissue. This probably depends, at least in part, on the level of inflammatory activation. Theoretically, it seems clear that nutritional status has to be improved in cardiac cachexia. It has been suggested that inflammatory activation in CHF may be due to endotoxin translocation through the edematous gut wall. Elevated endotoxin levels have been found in patients with acutely decompensated CHF, but these levels normalized with diuretic treatment. This finding may be of utmost importance. From one side it underscores the need for aggressive diuretic treatment to prevent translocation, from another side however, it suggests potential area for enteral treatment. Enteral route of nutrition may be highly beneficial by diminishing bacterial translocation from guts and/or endotoxin transfer, finally resulting in lower inflammatory activation Numerous experimental studies display that enteral feeding reduces bacterial translocation, endotoxin absorption and positively modulates function of local immune tissue.

A search of the literature shows that very little is known about the effectiveness of nutritional support on functional performance in cachectic CHF patients and actually no reports concern the influence of enteral feeding on immune activation of cachectic CHF patients. Recent information of some links existing between leptin, which is increased in CHF, and inflammatory activation in this syndrome speculate on a functional role of leptin in immune activation in CHF. As leptin is one of the most important hormones in the regulation of body energy metabolism, we think it is reasonable to look also into enteral feeding -induced changes of leptin and concomitant fluctuations of plasma cytokines.

During the last 12 months we have been using nutritional support in cachectic patients with CHF as an adjunct to standard therapy. We were surprised by a significant functional improvement that we observed in many instances. As most of these patients were subjected to aggressive multi-drug diuretic therapy as well, it was impossible to appreciate the role of enteral nutrition in this respect. We think, these observations are worth verification in more controlled prospective studies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 29
• Est. completion date: February 2002
• Est. primary completion date: February 2002
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Signing of informed consent,

• Patient with either gender with actual signs or symptoms of congestive heart failure of any origin with NYHA class no less then III,

• Presence of cardiac cachexia as defined above,

• Duration of symptoms of congestive heart failure of at least 6 months,

• Ejection fraction assessed by echocardiography =30%,

• Nutritional support will be offered solely to patients with their pharmacological treatment firmly established for at least 30 days.

Exclusion Criteria:

• Acute decompensation with clinically evident pulmonary or abdominal congestion,

• Any situation (apart from congestive heart failure) that may affect absorption of nutrients from the gut,

• Presence of active gastritis or ulcer,

• Presence of cancer,

• Presence of thyreotoxicosis,

• Type I diabetes mellitus,

• Pancreatic insufficiency,

• Treatment with ß-blockers,

• Clinically relevant liver disease with significantly elevated enzymes (ALAT or AspAT or ALP 4 times above normal according to local norms),

• Body mass index > 25,

• unstable angina pectoris or other acute coronary syndromes within last three months,

• Participation in any other studies,

• Signs of uncooperative attitude,

• Known HIV virus infection,

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cachexia
• Cardiac Cachexia
• Chronic Heart Failure
• Heart Failure

Intervention

Dietary Supplement:
• NutriDrink
Nutritional supplementation that contains 600 kcal/day: protein content 20 g, carbohydrates 72 g, fat 26 g
• Placebo
Nutritional supplementation containing only 12 kcal/day

Locations

Country	Name	City	State
Germany	Applied Cachexia Research, Department of Cardiology, Charité Medical School, Campus Virchow-Klinikum	Berlin
Poland	Silesian Center for Heart Diseases	Zabrze

Sponsors (2)

Lead Sponsor	Collaborator
National Heart and Lung Institute	Nutricia Research Fundation

Countries where clinical trial is conducted

Germany,  Poland, 

References & Publications (24)

Abel RM, Fischer JE, Buckley MJ, Barnett GO, Austen WG. Malnutrition in cardiac surgical patients. Results of a prospective, randomized evaluation of early postoperative parenteral nutrition. Arch Surg. 1976 Jan;111(1):45-50. — View Citation

Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, Poole-Wilson PA, Coats AJ. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation. 1997 Jul 15;96(2):526-34. — View Citation

Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, Harrington D, Kox WJ, Poole-Wilson PA, Coats AJ. Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997 Apr 12;349(9058):1050-3. Erratum in: Lancet 1997 Apr 26;349(9060):1258. — View Citation

Anker SD, Ponikowski PP, Clark AL, Leyva F, Rauchhaus M, Kemp M, Teixeira MM, Hellewell PG, Hooper J, Poole-Wilson PA, Coats AJ. Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure. Eur Heart J. 1999 May;20(9):683-93. — View Citation

Anker SD, Rauchhaus M. Insights into the pathogenesis of chronic heart failure: immune activation and cachexia. Curr Opin Cardiol. 1999 May;14(3):211-6. Review. — View Citation

Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984 Sep 27;311(13):819-23. — View Citation

Guihot G, Merle V, Leborgne M, Pivert G, Corriol O, Brousse N, Ricour C, Colomb V. Enteral nutrition modifies gut-associated lymphoid tissue in rat regardless of the molecular form of nitrogen supply. J Pediatr Gastroenterol Nutr. 1997 Feb;24(2):153-61. — View Citation

Haynes WG, Morgan DA, Walsh SA, Mark AL, Sivitz WI. Receptor-mediated regional sympathetic nerve activation by leptin. J Clin Invest. 1997 Jul 15;100(2):270-8. — View Citation

Haynes WG, Sivitz WI, Morgan DA, Walsh SA, Mark AL. Sympathetic and cardiorenal actions of leptin. Hypertension. 1997 Sep;30(3 Pt 2):619-23. Review. — View Citation

Heymsfield SB, Casper K. Congestive heart failure: clinical management by use of continuous nasoenteric feeding. Am J Clin Nutr. 1989 Sep;50(3):539-44. — View Citation

Joseph J, Gilbert EM. The sympathetic nervous system in chronic heart failure. Prog Cardiovasc Dis. 1998 Jul-Aug;41(1 Suppl 1):9-16. Review. — View Citation

Kotani J, Usami M, Nomura H, Iso A, Kasahara H, Kuroda Y, Oyanagi H, Saitoh Y. Enteral nutrition prevents bacterial translocation but does not improve survival during acute pancreatitis. Arch Surg. 1999 Mar;134(3):287-92. Erratum in: Arch Surg 1999 Jun;134(6):643. — View Citation

Levy JR, LeGall-Salmon E, Santos M, Pandak WM, Stevens W. Effect of enteral versus parenteral nutrition on leptin gene expression and release into the circulation. Biochem Biophys Res Commun. 1997 Aug 8;237(1):98-102. — View Citation

Leyva F, Anker SD, Egerer K, Stevenson JC, Kox WJ, Coats AJ. Hyperleptinaemia in chronic heart failure. Relationships with insulin. Eur Heart J. 1998 Oct;19(10):1547-51. — View Citation

Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM. Leptin regulates proinflammatory immune responses. FASEB J. 1998 Jan;12(1):57-65. — View Citation

Niebauer J, Volk HD, Kemp M, Dominguez M, Schumann RR, Rauchhaus M, Poole-Wilson PA, Coats AJ, Anker SD. Endotoxin and immune activation in chronic heart failure: a prospective cohort study. Lancet. 1999 May 29;353(9167):1838-42. — View Citation

Otaki M. Surgical treatment of patients with cardiac cachexia. An analysis of factors affecting operative mortality. Chest. 1994 May;105(5):1347-51. — View Citation

Paccagnella A, Calò MA, Caenaro G, Salandin V, Jus P, Simini G, Heymsfield SB. Cardiac cachexia: preoperative and postoperative nutrition management. JPEN J Parenter Enteral Nutr. 1994 Sep-Oct;18(5):409-16. — View Citation

Santos-Alvarez J, Goberna R, Sánchez-Margalet V. Human leptin stimulates proliferation and activation of human circulating monocytes. Cell Immunol. 1999 May 25;194(1):6-11. — View Citation

Sax HC, Illig KA, Ryan CK, Hardy DJ. Low-dose enteral feeding is beneficial during total parenteral nutrition. Am J Surg. 1996 Jun;171(6):587-90. — View Citation

Snitker S, Pratley RE, Nicolson M, Tataranni PA, Ravussin E. Relationship between muscle sympathetic nerve activity and plasma leptin concentration. Obes Res. 1997 Jul;5(4):338-40. — View Citation

Steele IC, Nugent AM, Maguire S, Hoper M, Campbell G, Halliday MI, Nicholls DP. Cytokine profile in chronic cardiac failure. Eur J Clin Invest. 1996 Nov;26(11):1018-22. — View Citation

Toth MJ, Gottlieb SS, Goran MI, Fisher ML, Poehlman ET. Daily energy expenditure in free-living heart failure patients. Am J Physiol. 1997 Mar;272(3 Pt 1):E469-75. — View Citation

Zhao SP, Zeng LH. Elevated plasma levels of tumor necrosis factor in chronic heart failure with cachexia. Int J Cardiol. 1997 Feb;58(3):257-61. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Weight (kg)		18 weeks	No
Primary	Quality of Life		18 weeks	No
Secondary	Lean tissue content, total plus arms and legs separately, as assessed by dual X-ray absorptiometry (DEXA)		18 weeks	No
Secondary	Fat tissue content, total plus arms and legs separately, as assessed by dual X-ray absorptiometry (DEXA)		18 weeks	No
Secondary	Serum levels of inflammatory markers including tumor necrosis factor, its soluble receptors 1 and 2, and interleukin-6		18 weeks	No
Secondary	Biochemistry markers including cholesterol, low density lipoprotein, high density lipoprotein		18 weeks	No
Secondary	Left ventricular ejection fraction as assessed by echocardiography		18 weeks	No
Secondary	Exercise testing using spiroergometry		18 weeks	No