Targeted medical nutrition for cachexia in chronic obstructive pulmonary disease: a randomized, controlled trial

Abstract

Background: Cachectic patients with chronic obstructive pulmonary disease (COPD) may benefit from nutritional support. This double-blind, randomized, controlled trial evaluated the safety and efficacy of targeted medical nutrition (TMN) vs. an isocaloric comparator in pre-cachectic and cachectic patients with COPD.

Methods: Patients aged ≥50 years with moderate-to-severe COPD and involuntary weight loss or low body mass index (16-18 kg/m2 ) were randomized 1:1 to receive TMN (~230 kcal; 2 g omega-3 fatty acids; 10 μg 25-hydroxy-vitamin D3) or isocaloric comparator twice daily for 12 weeks (ClinicalTrials.gov Identifier: NCT02442908). Primary safety endpoints comprised adverse events and changes in vital signs, laboratory parameters, and concomitant medications. Secondary efficacy endpoints included changes in weight, body composition, exercise tolerance, metabolic biomarkers, and systemic inflammation.

Results: Forty-five patients were randomized to receive TMN (n = 22; mean 69.2 years) or isocaloric comparator (n = 23; mean 69.7 years). TMN was well tolerated. Adverse events were similar in number and type in both groups. Compliance to both products was good (TMN, 79%; comparator, 77%). Both groups gained weight, but the TMN group gained comparatively more fat mass (P = 0.0013). Reductions in systolic blood pressure (P = 0.0418) and secondary endpoints of triglycerides (P = 0.0217) and exercise-induced fatigue (P = 0.0223) and dyspnoea (P = 0.0382), and increases in high-density lipoprotein cholesterol (P = 0.0254), were observed in the TMN vs. the comparator group by week 12.

Conclusions: Targeted medical nutrition containing high-dose omega-3 fatty acids, vitamin D, and high-quality protein is well tolerated with a good safety profile and has positive effects on blood pressure and blood lipids and on exercise-induced fatigue and dyspnoea. Therefore, this TMN could be clinically beneficial in the nutritional and metabolic support of pre-cachectic and cachectic patients with COPD.

Keywords: Cachexia; Chronic obstructive pulmonary disease; Nutrition; Omega-3 fatty acids; Pre-cachexia.

© 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Figures

Figure 1

Patient flow.

Figure 2

Change from baseline to week 12 in results of the 6 min walk test in the TMN group and the isocaloric comparator group. (A) Borg scale measured post‐walk fatigue and dyspnoea. (B) Distance covered. Data on figures show mean ± SEM change from baseline to week 12, calculated as week 12 value minus baseline value for each patient, divided by the n number; n = 19 for both groups. Data below figures show mean baseline and week 12 values, calculated as the mean of all values recorded. Effect sizes and P values were estimated by analysis of covariance adjusted for baseline value. *P < 0.05 for the TMN vs. isocaloric comparator group. CI, confidence interval; SEM, standard error of the mean; TMN, targeted medical nutrition.

Figure 3

Change in levels of markers of inflammation from baseline to week 12 in the TMN group and the isocaloric comparator group. Data on figures show mean ± SEM change from baseline to week 12, calculated as week 12 value minus baseline value for each patient, divided by the n number; n = 22 for both groups. Data below figures show mean baseline and week 12 values, calculated as the mean of all values recorded. Effect sizes and P values were estimated by analysis of covariance adjusted for baseline value. CI, confidence interval; CRP, C‐reactive protein; IL, interleukin; SEM, standard error of the mean; TMN, targeted medical nutrition; TNF, tumour necrosis factor.

Figure 4

Change from baseline to week 12 in scores on the St. George's Respiratory Questionnaire in the TMN group and the isocaloric comparator group. Data on figures show mean ± SEM change from baseline to week 12, calculated as week 12 value minus baseline value for each patient, divided by the n number; n = 22 for both groups. Data below figures show mean baseline and week 12 values, calculated as the mean of all values recorded. Effect sizes and P values were estimated by analysis of covariance adjusted for baseline value. CI, confidence interval; SEM, standard error of the mean; TMN, targeted medical nutrition.

Figure 5

Change from baseline to week 12 in the TMN group and the isocaloric comparator group. (A) Plasma omega‐3 to omega‐6 ratio. (B) Plasma vitamin D3 level. (C) EPA as a proportion of total plasma fatty acids. (D) DHA as a proportion of total plasma fatty acids. Data on figures show mean ± SEM change from baseline to week 12, calculated as week 12 value minus baseline value for each patient, divided by the n number; TMN group, n = 22; comparator group; n = 22–23. Data below figures show mean baseline and week 12 values, calculated as the mean of all values recorded. Effect sizes and P values were estimated by analysis of covariance adjusted for baseline value. *P < 0.0001 for the TMN group vs. the isocaloric comparator group. CI, confidence interval; DHA, docosahexaenoic acid; EPA, eicosapentaenoic acid; SEM, standard error of the mean; TMN, targeted medical nutrition.