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A Pilot Trial of Triheptanoin for People With Amyotrophic Lateral Sclerosis (PALS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03506425
Recruitment Status : Completed
First Posted : April 24, 2018
Results First Posted : December 24, 2019
Last Update Posted : December 24, 2019
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Richard Bedlack, M.D., Ph.D., Duke University

Brief Summary:
The causes of ALS are largely unknown. However, mitochondrial dysfunction, resulting in impaired energy production, oxidative stress and apoptosis, may play a key role in ALS progression. Triheptanoin 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. This pilot trial will determine if Triheptanoin is safe tolerable, alters biomarkers of brain energy metabolism and oxidative stress, and slows functional decline in people with ALS.

Condition or disease Intervention/treatment Phase
ALS Drug: Triheptanoin Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Trial of Triheptanoin for People With Amyotrophic Lateral Sclerosis (PALS)
Actual Study Start Date : June 21, 2018
Actual Primary Completion Date : March 28, 2019
Actual Study Completion Date : March 28, 2019


Arm Intervention/treatment
Experimental: Group 1
Standard care for 1 month, then standard care and Triheptanoin for 5 months.
Drug: 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.

Experimental: Group 2
Standard care and Triheptanoin for 6 months.
Drug: 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.

No Intervention: Group 3
Healthy controls for biomarkers



Primary Outcome Measures :
  1. ALS Functional Rating Scale-revised Version (ALSFRS-R) Slope [ Time Frame: baseline, 6 months ]
    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.


Secondary Outcome Measures :
  1. Change in NAA/Cr Ratio From Motor Cortex as Measured by Magnetic Resonance Spectroscopy [ Time Frame: baseline, 6 months ]
    Effects of time, Triheptanoin on NAA/Cr (N-acetylaspartate/creatine) ratio from motor cortex

  2. Change in Urine Isoprostane Levels, an Oxidative Stress Marker [ Time Frame: baseline, 1 month ]
    Effects of ALS and/or Triheptanoin on urine isoprostane levels (a marker of oxidative stress) at month 1



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Lab supported probable or more definite ALS by El Escorial Criteria
  2. Age greater than or equal to 18 years
  3. Willing and able to provide informed consent
  4. On riluzole at a stable dose for at least 30d or not taking this
  5. On Radicava at a stable dose for at least 30d or not taking this
  6. Life expectancy at least 6 months
  7. Currently managed on a reasonably stable diet, avoidance of fasting, carnitine or medium chain triglyceride (MCT) oils
  8. Must stop any other experimental ALS treatment for at least 30 days prior to screening
  9. If sexually active, must agree to use contraceptive or abstinence for duration of treatment with triheptanoin
  10. Females of child bearing age must have negative pregnancy test at screening

Exclusion Criteria:

  1. Unwilling or unable to provide informed consent
  2. Previous intolerance or adverse reaction to triheptanoin or MCT
  3. Conditions that will prohibit MRI scanning (metal in eye, some surgical implants, claustrophobia, inability to lie supine)
  4. Have any other co-morbid conditions that in the opinion of the study investigator, places the participant at increased risk of complications, interferes with study participation or compliance, or confounds study objectives

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03506425


Locations
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United States, North Carolina
Duke University
Durham, North Carolina, United States, 27705
Sponsors and Collaborators
Richard Bedlack, M.D., Ph.D.
Ultragenyx Pharmaceutical Inc
Investigators
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Principal Investigator: Richard S Bedlack, MD PhD Duke ALS Clinic
  Study Documents (Full-Text)

Documents provided by Richard Bedlack, M.D., Ph.D., Duke University:

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Responsible Party: Richard Bedlack, M.D., Ph.D., MD, PhD, Duke University
ClinicalTrials.gov Identifier: NCT03506425    
Other Study ID Numbers: Pro00092250
First Posted: April 24, 2018    Key Record Dates
Results First Posted: December 24, 2019
Last Update Posted: December 24, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share data from this small pilot trial

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases