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

NCT03506425 | Completed Phase 1 Results FDA Drug

• 1 other identifier: Pro00092250
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

ALS

Outcome Measures

Primary Outcomes (1)

• ALS Functional Rating Scale-revised Version (ALSFRS-R) Slope

  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.

  baseline, 6 months

Secondary Outcomes (2)

• Change in NAA/Cr Ratio From Motor Cortex as Measured by Magnetic Resonance Spectroscopy

  baseline, 6 months

• Change in Urine Isoprostane Levels, an Oxidative Stress Marker

  baseline, 1 month

Study Arms (3)

Group 1

EXPERIMENTAL

Standard care for 1 month, then standard care and Triheptanoin for 5 months.

Drug: Triheptanoin

Group 2

EXPERIMENTAL

Standard care and Triheptanoin for 6 months.

Drug: Triheptanoin

Group 3

NO INTERVENTION

Healthy controls for biomarkers

Interventions

Triheptanoin DRUG

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 1; Group 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Unwilling or unable to provide informed consent
• Previous intolerance or adverse reaction to triheptanoin or MCT
• Conditions that will prohibit MRI scanning (metal in eye, some surgical implants, claustrophobia, inability to lie supine)
• 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

Sponsors & Collaborators

• Richard Bedlack, M.D., Ph.D.: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

Duke University

Durham, North Carolina, 27705, United States

Location

MeSH Terms

Interventions

triheptanoin

Results Point of Contact

• Title: Richard Bedlack, M.D., Ph.D.
• Organization: Duke University

richard.bedlack@duke.edu

919-668-2839

Study Officials

• Richard S Bedlack, MD PhD

  Duke ALS Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 13, 2018
• First Posted: April 24, 2018
• Study Start: June 21, 2018
• Primary Completion: March 28, 2019
• Study Completion: March 28, 2019
• Last Updated: December 24, 2019
• Results First Posted: December 24, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)