A phase II, open-label clinical trial on the combination therapy with medium-chain triglycerides and ghrelin in patients with chronic obstructive pulmonary disease

Abstract

The aim of this study was to investigate the effect of activated ghrelin with dietary octanoic acids or medium-chain triglyceride (MCT) administration to underweight patient with chronic obstructive pulmonary disease (COPD). Eleven severe and very severe COPD patients received a 5-day treatment with edible MCT. Sequentially, 10 patients received a 3-week combination treatment with MCT and intravenous acyl ghrelin. Five-day MCT treatment increased endogenous acyl ghrelin (p = 0.0049), but the total ghrelin level was unchanged. MCT-ghrelin combination treatment improved the peak oxygen uptake (p = 0.0120) during whole treatment course. This effect was attributed to the resultant improvements in cardiac function by O₂ pulse, and to the difference between inspired and expired oxygen concentration rather than minute ventilation. Addition of dietary MCT to ghrelin treatment improved the aerobic capacity of underweight COPD patients, likely by mechanisms of increased O₂ delivery through improvements in primary cardiocirculatory and muscular crosstalk.

Keywords: Acylation; Circulation; Exercise; Muscle; Oxygen; Underweight.

Fig. 1

Trial profile

Fig. 2

a Time course of plasma acyl ghrelin after 5-day MCT or 3-week MCT–ghrelin combination treatment. Changes in plasma acyl ghrelin were evaluated at 7:00 a.m., 10:00 a.m., 2:00 p.m., and 4:00 p.m. among treatments. Significant changes in the treatments (p = 0.0097), and in the sampling timings (p = 0.0003) are confirmed by a linear mixed effect model. ^**p < 0.01, ^***p < 0.001 between different timings or treatments, using the least squares means Tukey’s honestly significant difference test. Open square, pre-treatment; closed square, after 5-day intake of MCT with octanoic acid C 8:0 alone; closed triangle, after 3-week MCT–ghrelin combination treatment. b Comparison of the changes in the plasma acyl ghrelin and free FA 8:0 levels during the treatment course of a 5-day intake of MCT alone, followed by 3-week MCT–ghrelin combination treatment. Significant increases in the plasma levels of free FA 8:0, obtained at 10:00 a.m. (p < 0.0001) and acyl ghrelin (p = 0.0072), obtained at 4:00 p.m. are confirmed by a linear mixed effect model. ^†p < 0.05, ^††p < 0.01, ^††††p < 0.0001, compared with the pre-treatment values, using the least squares means Tukey’s honestly significant difference test. Continuous line, plasma acyl ghrelin; dashed line, free FA 8:0. Data are presented as means with standard error. FA fatty acid, MCT medium-chain triglyceride

Fig. 3

Changes in the physiological variables after a 3-week combination treatment with octanoic acid C8:0 and ghrelin. Each physiological variable was obtained at peak exercise during incremental cardiopulmonary exercise testing. The changes in each variable during the treatment course are analyzed by a linear mixed effect model. Compared with pre-treatment, ^*p < 0.05, ^**p < 0.01 and compared with the values at week 3, ^†p < 0.05, ^††p < 0.01 using the least squares means Tukey’s honestly significant difference test. $\mathrm{\Delta }{F}_{O_2}$ inspired O₂ concentration minus expired O₂ concentration, MCT medium-chain triglyceride; O₂pulse$V_{{\text{O}}_2}^{\prime }$/heart rate, V′_E minute ventilation, $V_{O_2}^{\prime }$ oxygen uptake