Randomized Clinical Trial of Behavioral and Nutrition Treatment to Improve Energy Intake and Growth in Toddlers and Preschoolers With Cystic Fibrosis

Background Emerging data suggests a possible role for cysteamine as an adjunct treatment for pulmonary exacerbations of cystic fibrosis (CF) that continue to be a major clinical challenge. There are no studies investigating the use of cysteamine in pulmonary exacerbations of CF. This exploratory randomized clinical trial was conducted to answer the question: In future pivotal trials of cysteamine as an adjunct treatment in pulmonary exacerbations of CF, which candidate cysteamine dosing regimens should be tested and which are the most appropriate, clinically meaningful outcome measures to employ as endpoints? Methods and findings Multicentre double-blind randomized clinical trial. Adults experiencing a pulmonary exacerbation of CF being treated with standard care that included aminoglycoside therapy were randomized equally to a concomitant 14-day course of placebo, or one of 5 dosing regimens of cysteamine. Outcomes were recorded on days 0, 7, 14 and 21 and included sputum bacterial load and the patient reported outcome measures (PROMs): Chronic Respiratory Infection Symptom Score (CRISS), the Cystic Fibrosis Questionnaire–Revised (CFQ-R); FEV1, blood leukocyte count, and inflammatory markers. Eighty nine participants in fifteen US and EU centres were randomized, 78 completed the 14-day treatment period. Cysteamine had no significant effect on sputum bacterial load, however technical difficulties limited interpretation. The most consistent findings were for cysteamine 450mg twice daily that had effects additional to that observed with placebo, with improved symptoms, CRISS additional 9.85 points (95% CI 0.02, 19.7) p = 0.05, reduced blood leukocyte count by 2.46x109 /l (95% CI 0.11, 4.80), p = 0.041 and reduced CRP by geometric mean 2.57 nmol/l (95% CI 0.15, 0.99), p = 0.049. Conclusion In this exploratory study cysteamine appeared to be safe and well-tolerated. Future pivotal trials investigating the utility of cysteamine in pulmonary exacerbations of CF need to include the cysteamine 450mg doses and CRISS and blood leukocyte count as outcome measures. Clinical trial registration NCT03000348; www.clinicaltrials.gov.

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Beneficial Effects of Adenosine Triphosphate on Nutritional Status in Advanced Lung Cancer Patients: A Randomized Clinical Trial

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.2.371 ◽

2002 ◽

Vol 20 (2) ◽

pp. 371-378 ◽

Cited By ~ 15

Author(s):

Hendrik J. Agteresch ◽

Trinet Rietveld ◽

Leon G.M. Kerkhofs ◽

J. Willem O. van den Berg ◽

J. H. Paul Wilson ◽

...

Keyword(s):

Lung Cancer ◽

Clinical Trial ◽

Body Composition ◽

Body Weight ◽

Energy Expenditure ◽

Randomized Clinical Trial ◽

Energy Intake ◽

Advanced Lung Cancer ◽

Control Group ◽

Muscle Area

PURPOSE: In a randomized clinical trial in patients with advanced non–small-cell lung cancer (NSCLC), infusion with adenosine 5′-triphosphate (ATP) inhibited loss of body weight and quality of life. In the present article, the effects of ATP on body composition, energy intake, and energy expenditure as secondary outcome measures in the same patients are reported. PATIENTS AND METHODS: Patients with NSCLC, stage IIIB or IV, were randomized to receive either 10 intravenous, 30-hour ATP infusions every 2 to 4 weeks or no ATP. Fat mass (FM), fat-free mass (FFM), and arm muscle area were assessed at 4-week intervals for 28 weeks. Food intake, body cell mass (BCM), and resting energy expenditure (REE) were assessed at 8-week intervals for 16 weeks. Between-group differences were tested for statistical significance by repeated-measures analysis of covariance. RESULTS: Fifty-eight patients were randomized (28 ATP, 30 control). No change in body composition over the 28-week follow-up period was found in the ATP group, whereas, per 4 weeks, the control group lost 0.6 kg of FM (P = .004), 0.5 kg of FFM (P = .02), 1.8% of arm muscle area (P = .02), and 0.6% of BCM/kg body weight (P = .054) and decreased 568 KJ/d in energy intake (P = .0001). Appetite also remained stable in the ATP group but decreased significantly in the control group (P = .0004). No significant differences in REE between the ATP and control groups were observed. CONCLUSION: The inhibition of weight loss by ATP infusions in patients with advanced NSCLC is attributed to counteracting the loss of both metabolically active and inactive tissues. These effects are partly ascribed to maintenance of energy intake.

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