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

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Dietary Supplement: Oxepa; Dietary Supplement: Jevity 1.5; Dietary Supplement: Jevity 1.0	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Study Start Date: October 2009
• Actual Primary Completion Date: April 2013
• Actual Study Completion Date: May 2013

Arms and Interventions

Arm	Intervention/treatment
Experimental: High fat/high calorie; High fat/high calorie diet: Oxepa	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.
Active Comparator: High calorie; High calorie diet: Jevity 1.5	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.
Placebo Comparator: Control; Control diet: Jevity 1.0	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.

Outcome Measures

Primary Outcome Measures :

1. Safety Outcomes: Frequency of Adverse Events [ Time Frame: 5 months ]
2. Serious Adverse Events [ Time Frame: 5 months ]
   SAE were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
3. Tolerability [ Time Frame: 5 months ]
   Number of participants who completed the study on their assigned study intervention.

Secondary Outcome Measures :

1. 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.
2. Biomarkers of Body Composition and Lipid Metabolism [ Time Frame: 5 months follow-up ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arizona

Barrow Neurological Institute/St. Joseph's Hospital and Medical Center

Phoenix, Arizona, United States, 85013

United States, California

University of California at Irvine

Irvine, California, United States, 92868

California Pacific Medical Center, University of California at San Francisco

San Francisco, California, United States, 94120

United States, Florida

Sarasota Memorial Hospital

Sarasota, Florida, United States, 34239

United States, Georgia

Emory University School of Medicine

Atlanta, Georgia, United States, 30322

United States, Massachusetts

Neurology Clinical Trials Unit, Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, Michigan

Saint Mary's Health Care

Grand Rapids, Michigan, United States, 49503

United States, New York

Columbia Presbyterian Medical Center

New York, New York, United States, 10032

United States, North Carolina

Carolinas Medical Center Neuromuscular/ALS-MDA Center

Charlotte, North Carolina, United States, 28207

United States, Oregon

Oregan Health and Science University

Portland, Oregon, United States, 97239

United States, Pennsylvania

Drexel University

Philadelphia, Pennsylvania, United States, 19107

United States, Texas

Methodist Neurological Institute

Houston, Texas, United States, 77030

United States, Vermont

University of Vermont

Burlington, Vermont, United States, 05401

Sponsors and Collaborators

Massachusetts General Hospital

Muscular Dystrophy Association

Investigators

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

More Information

Publications of Results:

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.

Other 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. doi: 10.1093/ajcn/63.1.130.

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. doi: 10.1159/000089626.

Desport JC, Preux PM, Magy L, Boirie Y, Vallat JM, Beaufrere B, Couratier P. Factors correlated with hypermetabolism in patients with amyotrophic lateral sclerosis. Am J Clin Nutr. 2001 Sep;74(3):328-34. doi: 10.1093/ajcn/74.3.328.

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. doi: 10.1136/jnnp.2005.083378. 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. doi: 10.1385/nmm:9:1:17.

Dupuis L, Oudart H, Rene 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. doi: 10.1073/pnas.0402026101. Epub 2004 Jul 19.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Anne-Marie Alexandra Wills, MD, Assistant Professor of Neurology, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT00983983
• Other Study ID Numbers: MDA136152; 2009-P-001132
• First Posted: September 24, 2009
• Results First Posted: February 27, 2015
• Last Update Posted: February 27, 2015
• Last Verified: February 2015

Keywords provided by Anne-Marie Alexandra Wills, MD, Massachusetts General Hospital:

Amyotrophic Lateral Sclerosis; ALS; Motor Neuron Disease; MND; Fat; Lipid; Cholesterol; Omega-3 fatty acid; Diet; Tube feed; Gastrostomy; PEG; Adults with Amyotrophic Lateral Sclerosis (ALS)

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases