High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis

Tracking Information
First Submitted Date ICMJE	September 23, 2009
First Posted Date ICMJE	September 24, 2009
Results First Submitted Date	September 16, 2014
Results First Posted Date	February 27, 2015
Last Update Posted Date	February 27, 2015
Study Start Date ICMJE	October 2009
Actual Primary Completion Date	April 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: February 11, 2015)	Safety Outcomes: Frequency of Adverse Events [ Time Frame: 5 months ]; Serious Adverse Events [ Time Frame: 5 months ]SAE were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.; Tolerability [ Time Frame: 5 months ]Number of participants who completed the study on their assigned study intervention.
Original Primary Outcome Measures ICMJE; (submitted: September 23, 2009)	Adverse events and subject compliance rates. [ Time Frame: 5 months follow-up ]
Change History	Complete list of historical versions of study NCT00983983 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: February 11, 2015)	Rate of Change in ALSFRS-R in Units/Month [ Time Frame: Over 5 months ]Rate of change in the ALS Functional Rating Scale-Revised, calculated in units/month. Negative numbers refer to worsening over time.; Biomarkers of Body Composition and Lipid Metabolism [ Time Frame: 5 months follow-up ]
Original Secondary Outcome Measures ICMJE; (submitted: September 23, 2009)	Biomarkers of Body Composition and Lipid Metabolism [ Time Frame: 5 months follow-up ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis
Official Title ICMJE	Phase II Safety and Tolerability Study of High Fat/High Calorie Versus High Calorie Versus Optimal Nutrition in Subjects With Amyotrophic Lateral Sclerosis
Brief Summary	The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of long-term use of high fat/high calorie and high calorie diets in people with amyotrophic lateral sclerosis (ALS) (Lou Gehrig's disease).
Detailed Description	Weight loss is a common and severe symptom of amyotrophic lateral sclerosis (ALS), caused both from inadequate calorie intake and an increased metabolic rate. People with ALS are generally instructed to increase their calorie intake; however, the ideal amount and type of calories has not been studied. Several studies in an animal model of motor neuron disease have shown that a high fat/high calorie diet can increase survival by as much as 38%. Mice on a high fat diet also live longer than mice fed diets consisting of high protein or high sugar. We are therefore conducting a phase II safety, tolerability, and preliminary efficacy trial in ALS of high fat versus high calorie versus normal diet. The normal diet will be calculated based on the number of calories needed to replace each participant's measured daily calorie requirement.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition ICMJE	Amyotrophic Lateral Sclerosis
Intervention ICMJE	Dietary Supplement: Oxepa Oxepa: Tube feed containing 1.5 calories/ml of which 55% calories are from fat, including eicosapentaenoic acid and gamma-linolenic acid. Subjects will receive 1.25 times their daily caloric requirements based on their measured resting energy expenditure. Subjects will receive 4 months of tube feeds and be followed for an additional 1 month to measure adverse events and tolerability.; Dietary Supplement: Jevity 1.5 Jevity 1.5: Tube feed containing 1.5 calories/ml of which 29.4% are from fat. Subjects will receive 1.25 times their daily caloric requirements based on their measured resting energy expenditure. Subjects will receive 4 months of tube feeds and be followed for an additional 1 month to measure adverse events and tolerability.; Dietary Supplement: Jevity 1.0 Jevity 1.0: Control tube feed. Subjects will receive 1.0 times their daily caloric requirements based on their measured resting energy expenditure. Subjects will receive 4 months of tube feeds and be followed for an additional 1 month to measure adverse events and tolerability.
Study Arms	Experimental: High fat/high calorie High fat/high calorie diet: Oxepa Intervention: Dietary Supplement: Oxepa; Active Comparator: High calorie High calorie diet: Jevity 1.5 Intervention: Dietary Supplement: Jevity 1.5; Placebo Comparator: Control Control diet: Jevity 1.0 Intervention: Dietary Supplement: Jevity 1.0
Publications *	Kasarskis EJ, Berryman S, Vanderleest JG, Schneider AR, McClain CJ. Nutritional status of patients with amyotrophic lateral sclerosis: relation to the proximity of death. Am J Clin Nutr. 1996 Jan;63(1):130-7.; Desport JC, Torny F, Lacoste M, Preux PM, Couratier P. Hypermetabolism in ALS: correlations with clinical and paraclinical parameters. Neurodegener Dis. 2005;2(3-4):202-7.; Desport JC, Preux PM, Magy L, Boirie Y, Vallat JM, Beaufrère B, Couratier P. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr. 2001 Sep;74(3):328-34.; Morozova N, Weisskopf MG, McCullough ML, Munger KL, Calle EE, Thun MJ, Ascherio A. Diet and amyotrophic lateral sclerosis. Epidemiology. 2008 Mar;19(2):324-37. doi: 10.1097/EDE.0b013e3181632c5d.; Veldink JH, Kalmijn S, Groeneveld GJ, Wunderink W, Koster A, de Vries JH, van der Luyt J, Wokke JH, Van den Berg LH. Intake of polyunsaturated fatty acids and vitamin E reduces the risk of developing amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2007 Apr;78(4):367-71. Epub 2006 Apr 28. Erratum in: J Neurol Neurosurg Psychiatry. 2007 Jul;78(7):779.; Mattson MP, Cutler RG, Camandola S. Energy intake and amyotrophic lateral sclerosis. Neuromolecular Med. 2007;9(1):17-20.; Dupuis L, Oudart H, René F, Gonzalez de Aguilar JL, Loeffler JP. Evidence for defective energy homeostasis in amyotrophic lateral sclerosis: benefit of a high-energy diet in a transgenic mouse model. Proc Natl Acad Sci U S A. 2004 Jul 27;101(30):11159-64. Epub 2004 Jul 19.; Wills AM, Hubbard J, Macklin EA, Glass J, Tandan R, Simpson EP, Brooks B, Gelinas D, Mitsumoto H, Mozaffar T, Hanes GP, Ladha SS, Heiman-Patterson T, Katz J, Lou JS, Mahoney K, Grasso D, Lawson R, Yu H, Cudkowicz M; MDA Clinical Research Network. Hypercaloric enteral nutrition in patients with amyotrophic lateral sclerosis: a randomised, double-blind, placebo-controlled phase 2 trial. Lancet. 2014 Jun 14;383(9934):2065-2072. doi: 10.1016/S0140-6736(14)60222-1. Epub 2014 Feb 28.; Paganoni S, Deng J, Jaffa M, Cudkowicz ME, Wills AM. Body mass index, not dyslipidemia, is an independent predictor of survival in amyotrophic lateral sclerosis. Muscle Nerve. 2011 Jul;44(1):20-4. doi: 10.1002/mus.22114. Epub 2011 May 23.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: July 1, 2013)	28
Original Estimated Enrollment ICMJE; (submitted: September 23, 2009)	60
Actual Study Completion Date	May 2013
Actual Primary Completion Date	April 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Clinical diagnosis of ALS; Male or female subjects aged 18 years or older; Must already be tolerating tube feedings through either a gastrostomy tube (G-tube or PEG) or jejunostomy tube (J-tube); Must require non-invasive ventilation (BIPAP) for less than 10 hours/day; Women of childbearing potential must have a negative pregnancy test at screening and be non-lactating. Exclusion Criteria: History of hepatitis including non-alcoholic steatohepatitis (NASH), cholecystectomy, prior biliary disease such as gallstones; History of diabetes; History of prior myocardial infarction or stroke; Laboratory values: Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.0 times the upper limit of normal or total bilirubin greater than 1.5 times the upper limit of normal; Allergy to soy, fish, or milk products
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00983983
Other Study ID Numbers ICMJE	MDA136152; 2009-P-001132
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Anne-Marie Alexandra Wills, MD, Massachusetts General Hospital
Study Sponsor ICMJE	Massachusetts General Hospital
Collaborators ICMJE	Muscular Dystrophy Association
Investigators ICMJE	Principal Investigator: Anne-Marie A Wills, M.D. Massachusetts General Hospital
PRS Account	Massachusetts General Hospital
Verification Date	February 2015
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP