Trial Outcomes & Findings for A Pilot Trial of Triheptanoin for People With Amyotrophic Lateral Sclerosis (PALS) (NCT NCT03506425)
NCT ID: NCT03506425
Last Updated: 2019-12-24
Results Overview
Amyotrophic lateral sclerosis functional rating scale-revised version (ALSFRS-R) is used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS and each is scored between 0 (no function at all) and 4 (normal function). Thus the overall score for this measure can range from 0 to 48, with higher scores indicating more normal function. The test-retest reliability is greater than 0.88 for all 12 items/activities. The ALSFRS-R declines linearly with time over a wide range during the course of ALS and the minimum clinically significant change in this scale is said to be 20%. The primary analysis in this study is the slope of the ALSFRS-R during treatment compared to pre-treatment. Pre-treatment slope for each participant will be estimated as follows: (48-enrollment ALSFRS-R)/months since symptom onset. This frequently used "pre-slope" method is simple and inexpensive, and can predict disease progression.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
15 participants
Primary outcome timeframe
baseline, 6 months
Results posted on
2019-12-24
Participant Flow
Participant milestones
| Measure |
Group 1
Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
Healthy controls for biomarkers
|
|---|---|---|---|
|
Overall Study
STARTED
|
5
|
5
|
5
|
|
Overall Study
COMPLETED
|
3
|
2
|
4
|
|
Overall Study
NOT COMPLETED
|
2
|
3
|
1
|
Reasons for withdrawal
| Measure |
Group 1
Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
Healthy controls for biomarkers
|
|---|---|---|---|
|
Overall Study
Adverse Event
|
1
|
3
|
0
|
|
Overall Study
Death
|
1
|
0
|
0
|
|
Overall Study
Withdrawal by Subject
|
0
|
0
|
1
|
Baseline Characteristics
A Pilot Trial of Triheptanoin for People With Amyotrophic Lateral Sclerosis (PALS)
Baseline characteristics by cohort
| Measure |
Group 1
n=5 Participants
Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
n=5 Participants
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
n=5 Participants
Healthy controls for biomarkers
|
Total
n=15 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Continuous
|
56.8 years
STANDARD_DEVIATION 11.3 • n=5 Participants
|
59.0 years
STANDARD_DEVIATION 14.4 • n=7 Participants
|
55.6 years
STANDARD_DEVIATION 14.4 • n=5 Participants
|
57.1 years
STANDARD_DEVIATION 13.4 • n=4 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Region of Enrollment
United States
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: baseline, 6 monthsPopulation: For the primary outcome measure, patients in Arm 1 and Arm 2 were combined (since patients in both these groups received at least 5 months of Triheptanoin). The primary outcome comparison is not between these arms, but between all these Triheptanoin-treated patients' ALSFRS-R progression during the study compared to progression before the study.
Amyotrophic lateral sclerosis functional rating scale-revised version (ALSFRS-R) is used to determine patients' assessments of their capability and independence in 12 functional activities. All 12 activities are relevant in ALS and each is scored between 0 (no function at all) and 4 (normal function). Thus the overall score for this measure can range from 0 to 48, with higher scores indicating more normal function. The test-retest reliability is greater than 0.88 for all 12 items/activities. The ALSFRS-R declines linearly with time over a wide range during the course of ALS and the minimum clinically significant change in this scale is said to be 20%. The primary analysis in this study is the slope of the ALSFRS-R during treatment compared to pre-treatment. Pre-treatment slope for each participant will be estimated as follows: (48-enrollment ALSFRS-R)/months since symptom onset. This frequently used "pre-slope" method is simple and inexpensive, and can predict disease progression.
Outcome measures
| Measure |
All Completed Subjects - Groups 1 and 2
n=5 Participants
Group 1: Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Group 2: Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
Healthy controls for biomarkers
|
|---|---|---|---|
|
ALS Functional Rating Scale-revised Version (ALSFRS-R) Slope
ALSFRS-R During Treatment
|
-0.39 points per month
Standard Deviation 0.44
|
—
|
—
|
|
ALS Functional Rating Scale-revised Version (ALSFRS-R) Slope
ALSFRS-R Before Treatment
|
-0.57 points per month
Standard Deviation 0.43
|
—
|
—
|
SECONDARY outcome
Timeframe: baseline, 6 monthsPopulation: One subject in Group 2 did not complete the second MRS measure. Group 3 did not receive treatment; therefore, no data was collected on Group 3 for this outcome measure.
Effects of time, Triheptanoin on NAA/Cr (N-acetylaspartate/creatine) ratio from motor cortex
Outcome measures
| Measure |
All Completed Subjects - Groups 1 and 2
n=5 Participants
Group 1: Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Group 2: Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
n=4 Participants
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
Healthy controls for biomarkers
|
|---|---|---|---|
|
Change in NAA/Cr Ratio From Motor Cortex as Measured by Magnetic Resonance Spectroscopy
|
0.4188 NAA/Cr
Standard Deviation 0.1923
|
0.0875 NAA/Cr
Standard Deviation 0.3013
|
—
|
SECONDARY outcome
Timeframe: baseline, 1 monthPopulation: One subject in Group 2 did not complete the month 1 visit.
Effects of ALS and/or Triheptanoin on urine isoprostane levels (a marker of oxidative stress) at month 1
Outcome measures
| Measure |
All Completed Subjects - Groups 1 and 2
n=5 Participants
Group 1: Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Group 2: Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
n=4 Participants
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
n=5 Participants
Healthy controls for biomarkers
|
|---|---|---|---|
|
Change in Urine Isoprostane Levels, an Oxidative Stress Marker
|
0.33 ng/mg
Standard Deviation 0.38
|
0.32 ng/mg
Standard Deviation 0.10
|
0.26 ng/mg
Standard Deviation 0.12
|
Adverse Events
Group 1
Serious events: 1 serious events
Other events: 5 other events
Deaths: 1 deaths
Group 2
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Group 3
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1
n=5 participants at risk
Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
n=5 participants at risk
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
n=5 participants at risk
Healthy controls for biomarkers
|
|---|---|---|---|
|
Nervous system disorders
Death
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Respiratory, thoracic and mediastinal disorders
Hypercarbic respiratory failure
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
0.00%
0/5 • 6 months
|
Other adverse events
| Measure |
Group 1
n=5 participants at risk
Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 2
n=5 participants at risk
Standard care and Triheptanoin for 6 months.
Triheptanoin: Triheptanoin is a medium chain triglyceride (MCT) that can improve mitochondrial function and energy production and therefore has potential for slowing ALS progression. Indeed, triheptanoin slowed motor neuron loss and delayed the onset of weakness in a mutant SOD1 model of ALS. The Triheptanoin we will use is a colorless to light yellow oil. The target triheptanoin dose for this study is 1g/kg/d. This target dose was selected because it was safe and tolerable and altered brain MR spectroscopy in patients with Huntington's Disease.
|
Group 3
n=5 participants at risk
Healthy controls for biomarkers
|
|---|---|---|---|
|
Gastrointestinal disorders
Increased AST and ALT
|
0.00%
0/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Leg pain
|
20.0%
1/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Weight loss
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Stomach cramps
|
0.00%
0/5 • 6 months
|
40.0%
2/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Weight gain
|
20.0%
1/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/5 • 6 months
|
60.0%
3/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Nausea
|
80.0%
4/5 • 6 months
|
40.0%
2/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Gastrointestinal disorders
Anorexia
|
20.0%
1/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Infections and infestations
Upper respiratory infection
|
20.0%
1/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Infections and infestations
Urinary tract infection
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
Hoarseness
|
20.0%
1/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
Fatigue
|
0.00%
0/5 • 6 months
|
40.0%
2/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
Vertigo
|
0.00%
0/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
|
Nervous system disorders
Increased weakness
|
0.00%
0/5 • 6 months
|
20.0%
1/5 • 6 months
|
0.00%
0/5 • 6 months
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place