TY - JOUR
T1 - Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis
T2 - A randomised, double-blind, placebo-controlled phase 2 trial
AU - Wills, Anne Marie
AU - Hubbard, Jane
AU - Macklin, Eric A.
AU - Glass, Jonathan
AU - Tandan, Rup
AU - Simpson, Ericka P.
AU - Brooks, Benjamin
AU - Gelinas, Deborah
AU - Mitsumoto, Hiroshi
AU - Mozaffar, Tahseen
AU - Hanes, Gregory P.
AU - Ladha, Shafeeq S.
AU - Heiman-Patterson, Terry
AU - Katz, Jonathan
AU - Lou, Jau Shin
AU - Mahoney, Katy
AU - Grasso, Daniela
AU - Lawson, Robert
AU - Yu, Hong
AU - Cudkowicz, Merit
N1 - Funding Information:
This study was supported by the Muscular Dystrophy Association (MDA), with additional support from the Massachusetts General Hospital Clinical Research Center (grant number 1 UL1 RR025758-03 ), Harvard Clinical and Translational Science Center, National Center for Research Resources of the National Institutes of Health (grant number RR-00109 ), and the Harvard NeuroDiscovery Center. The tube-feeding formulas used in this study were purchased at cost from Abbott Pharmaceuticals who provided no financial support for the study. We thank Jeremy Shefner, Wendy Galpern, and Michael McDermott for serving on the data and safety monitoring board. We thank Valerie Cwik, Sanjay Bidichandani, Karen L Smith, Jodi Wolff, and Jane Larkindale at the MDA for their unwavering support for this project. We thank the Northeast ALS Consortium, Lucie Bruijn and the ALS Association, and Apria Healthcare for helping to publicise the study. We would also like to thank Roy Cutler, Hideo Makimura, and Robert H Brown Jr for their useful discussions. Finally we wish to thank all the patients and their family members and caregivers who volunteered their time and effort to participate in this study.
PY - 2014
Y1 - 2014
N2 - Background: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. Methods: In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. Findings: Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0·06; HC/HC vs control, p=0·06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0·0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0·03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. Interpretation: Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. Funding: Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.
AB - Background: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition. Methods: In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983. Findings: Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0·06; HC/HC vs control, p=0·06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0·0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0·03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group. Interpretation: Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease. Funding: Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center.
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U2 - 10.1016/S0140-6736(14)60222-1
DO - 10.1016/S0140-6736(14)60222-1
M3 - Article
C2 - 24582471
AN - SCOPUS:84902314640
SN - 0140-6736
VL - 383
SP - 2065
EP - 2072
JO - The Lancet
JF - The Lancet
IS - 9934
ER -