High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase II Safety and Tolerability Study of High Fat/High Calorie Versus High Calorie Versus Optimal Nutrition in Subjects With Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Dietary Supplement: Oxepa
* Dietary Supplement: Jevity 1.5
* Dietary Supplement: Jevity 1.0


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High fat/high calorie<br>High fat/high calorie diet: Oxepa | Dietary Supplement: Oxepa<br>* 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.<br>|
| Active Comparator: High calorie<br>High calorie diet: Jevity 1.5 | Dietary Supplement: Jevity 1.5<br>* 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.<br>|
| Placebo Comparator: Control<br>Control diet: Jevity 1.0 | Dietary Supplement: Jevity 1.0<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Outcomes: Frequency of Adverse Events |  | 5 months | 
| Serious Adverse Events | SAE were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. | 5 months | 
| Tolerability | Number of participants who completed the study on their assigned study intervention. | 5 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Biomarkers of Body Composition and Lipid Metabolism |  | 5 months follow-up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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)