High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis

• ClinicalTrials.gov Identifier: NCT00983983
• Recruitment Status: Completed
• First Posted: September 24, 2009
• Results First Posted: February 27, 2015
• Last Update Posted: February 27, 2015
• Sponsor: Massachusetts General Hospital
• Collaborator: Muscular Dystrophy Association
• Information provided by (Responsible Party): Anne-Marie Alexandra Wills, MD, Massachusetts General Hospital

Tracking Information

• First Submitted Date: September 23, 2009
• First Posted Date: 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: October 2009
• Actual Primary Completion Date: April 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 (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 (submitted: September 23, 2009): Biomarkers of Body Composition and Lipid Metabolism [ Time Frame: 5 months follow-up ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis

Intervention

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 1, 2013): 28
• Original Estimated Enrollment (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

Inclusion Criteria:

1. Clinical diagnosis of ALS
2. Male or female subjects aged 18 years or older
3. Must already be tolerating tube feedings through either a gastrostomy tube (G-tube or PEG) or jejunostomy tube (J-tube)
4. Must require non-invasive ventilation (BIPAP) for less than 10 hours/day
5. Women of childbearing potential must have a negative pregnancy test at screening and be non-lactating.

Exclusion Criteria:

1. History of hepatitis including non-alcoholic steatohepatitis (NASH), cholecystectomy, prior biliary disease such as gallstones
2. History of diabetes
3. History of prior myocardial infarction or stroke
4. 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
5. Allergy to soy, fish, or milk products

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00983983
• Other Study ID Numbers: 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: Massachusetts General Hospital
• Collaborators: Muscular Dystrophy Association

Investigators

• Principal Investigator: Anne-Marie A Wills, M.D.; Massachusetts General Hospital

• PRS Account: Massachusetts General Hospital
• Verification Date: February 2015