Amyotrophic Lateral Sclerosis
Conditions
Keywords
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)
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.
Interventions
DIETARY_SUPPLEMENTOxepa
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_SUPPLEMENTJevity 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_SUPPLEMENTJevity 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.
Sponsors
Muscular Dystrophy Association
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety Outcomes: Frequency of Adverse Events | 5 months | — |
| Serious Adverse Events | 5 months | SAE were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. |
| Tolerability | 5 months | Number of participants who completed the study on their assigned study intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Change in ALSFRS-R in Units/Month | 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 | 5 months follow-up | — |
Countries
United States
Participant flow
Pre-assignment details
4 participants were screened but excluded due to not meeting inclusion criteria (1 due to history of Myocardial Infarction, 1 due to Diabetes, 1 due to low forced vital capacity, and 1 due to the investigator's judgment).
Participants by arm
| Arm | Count |
|---|---|
| High Fat/High Calorie High fat/high calorie diet: Oxepa
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. | 8 |
| High Calorie/High Carbohydrate High calorie diet: Jevity 1.5
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. | 9 |
| Control Control diet: Jevity 1.0
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. | 7 |
| Total | 24 |
Baseline characteristics
| Characteristic | High Fat/High Calorie | High Calorie/High Carbohydrate | Control | Total |
|---|---|---|---|---|
| Age, Continuous | 64.0 years STANDARD_DEVIATION 6.9 | 57.5 years STANDARD_DEVIATION 15.4 | 63.2 years STANDARD_DEVIATION 9.4 | 61.3 years STANDARD_DEVIATION 11.4 |
| Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) | 30.7 units on a scale STANDARD_DEVIATION 7 | 25.5 units on a scale STANDARD_DEVIATION 9.4 | 23.0 units on a scale STANDARD_DEVIATION 3.5 | 26.3 units on a scale STANDARD_DEVIATION 7.6 |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 1 Participants | 11 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 6 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 6 | 8 / 8 | 6 / 6 |
| serious Total, serious adverse events | 3 / 6 | 0 / 8 | 4 / 6 |
Outcome results
Primary
Safety Outcomes: Frequency of Adverse Events
Time frame: 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Fat/High Calorie | Safety Outcomes: Frequency of Adverse Events | 49 Total Number of Adverse Events |
| High Calorie/High Carbohydrate | Safety Outcomes: Frequency of Adverse Events | 24 Total Number of Adverse Events |
| Control | Safety Outcomes: Frequency of Adverse Events | 42 Total Number of Adverse Events |
p-value: 0.06Fisher Exact
Primary
Serious Adverse Events
SAE were defined using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.
Time frame: 5 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Fat/High Calorie | Serious Adverse Events | 3 Number of Serious Adverse Events |
| High Calorie/High Carbohydrate | Serious Adverse Events | 0 Number of Serious Adverse Events |
| Control | Serious Adverse Events | 9 Number of Serious Adverse Events |
p-value: 0.0005Fisher Exact
Primary
Tolerability
Number of participants who completed the study on their assigned study intervention.
Time frame: 5 months
Population: The number of participants who received the study diet (4 participants withdrew consent prior to receiving study intervention).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| High Fat/High Calorie | Tolerability | 5 participants |
| High Calorie/High Carbohydrate | Tolerability | 7 participants |
| Control | Tolerability | 1 participants |
p-value: 0.03Fisher Exact
Secondary
Biomarkers of Body Composition and Lipid Metabolism
Time frame: 5 months follow-up
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.
Time frame: Over 5 months
| Arm | Measure | Value (MEAN) |
|---|---|---|
| High Fat/High Calorie | Rate of Change in ALSFRS-R in Units/Month | -1.54 units on a scale/month |
| High Calorie/High Carbohydrate | Rate of Change in ALSFRS-R in Units/Month | -1.07 units on a scale/month |
| Control | Rate of Change in ALSFRS-R in Units/Month | -2.17 units on a scale/month |
Comparison: Change over time in the ALSFRS-R was analyzed using random-slopes modelsp-value: 0.07Mixed Models Analysis