High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis

Amyotrophic Lateral Sclerosis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00983983
• Other study ID #: MDA136152
• Secondary ID: 2009-P-001132
• Status: Completed
• Phase: Phase 2
• First received: September 23, 2009
• Last updated: February 11, 2015
• Start date: October 2009
• Est. completion date: May 2013

Study information

• Verified date: February 2015
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: May 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
United States	Emory University School of Medicine	Atlanta	Georgia
United States	Neurology Clinical Trials Unit, Massachusetts General Hospital	Boston	Massachusetts
United States	University of Vermont	Burlington	Vermont
United States	Carolinas Medical Center Neuromuscular/ALS-MDA Center	Charlotte	North Carolina
United States	Saint Mary's Health Care	Grand Rapids	Michigan
United States	Methodist Neurological Institute	Houston	Texas
United States	University of California at Irvine	Irvine	California
United States	Columbia Presbyterian Medical Center	New York	New York
United States	Drexel University	Philadelphia	Pennsylvania
United States	Barrow Neurological Institute/St. Joseph's Hospital and Medical Center	Phoenix	Arizona
United States	Oregan Health and Science University	Portland	Oregon
United States	California Pacific Medical Center, University of California at San Francisco	San Francisco	California
United States	Sarasota Memorial Hospital	Sarasota	Florida

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Muscular Dystrophy Association

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Mattson MP, Cutler RG, Camandola S. Energy intake and amyotrophic lateral sclerosis. Neuromolecular Med. 2007;9(1):17-20. — View Citation

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. — View Citation

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. — View Citation

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. Hypercal — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Outcomes: Frequency of Adverse Events		5 months	Yes
Primary	Serious Adverse Events	SAE were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.	5 months	Yes
Primary	Tolerability	Number of participants who completed the study on their assigned study intervention.	5 months	No
Secondary	Rate of Change in ALSFRS-R in Units/Month	Rate of change in the ALS Functional Rating Scale-Revised, calculated in units/month. Negative numbers refer to worsening over time.	Over 5 months	Yes
Secondary	Biomarkers of Body Composition and Lipid Metabolism		5 months follow-up	No