Clinical trial NCT04244630: Mitochondrial Capacity Boost in ALS (MICABO-ALS) Trial
Official title: Mitochondrial Capacity Boost in ALS (MICABO-ALS) Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Lead sponsor: Dallas VA Medical Center
Sponsor class: FED
First posted: 2020-01-28
Enrollment: 60
Sex: ALL
Minimum age (years): 21
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this research is to investigate the validity of a previous clinical trial named EH301, which showed beneficial effects of anti-oxidant therapies in patients with amyotrophic lateral sclerosis (ALS). If validated by this study, providing over-the-counter anti-oxidants would be a simple, low risk, low-cost approach to significantly slow or stop the progression of ALS, for which currently no effective treatment exists. It is currently thought that oxidative stress is a major cause of ALS. The study investigators are therefore planning to expand the original scope of the previous trial by including anti-oxidants at high doses that were not previously used. All of these compounds are considered safe.

Detailed description: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that affects muscle function throughout the body. Weakness and muscle shrinkage begin either in the face, arm, or leg. A clinical ALS hallmark is rapidly progressive weight loss. Also, respiration is usually affected late in the disease, and death typically occurs as a consequence of respiratory failure. The median survival after disease onset is approximately 3-4 years.

While there are now two FDA-approved agents for patients with ALS, there are no interventions that have had a meaningful impact on the natural course of this disease. Riluzole prolongs survival by up to 12 weeks. Edaravone improves some aspects of neurological function in a small subset of patients, but that was ineffective in clinical studies that included ALS patients at all stages of disease.

Past failures to identify effective therapies reflect the complexity of ALS pathogenesis, in that no single therapeutic target has been identified. Thus, single agent or dual combination therapies are unlikely to succeed. Given the truly rapid and devastating nature of ALS and that there are no effective treatments for ALS, one can argue that it is critical to devise a different approach. Until the exact mechanisms that lead to ALS are identified, it is necessary to employ polytherapy which includes new agents that show promise.

This study will lay further groundwork on methodology for performing more definite trials in ALS. The study of secondary biomarkers in ALS is significant because there are currently no molecular or biochemical biomarkers for assessing therapeutic efficacy of drug treatments in ALS clinical trials. By doing this study, the study investigators hope to learn that high-dose anti-oxidants would be a simple, low risk, low-cost approach to significantly slow or stop the progression of ALS, for which currently no effective treatment exists. Participation in this research will last about 13 months

Eligibility criteria: Inclusion Criteria:

1. A clinical diagnosis by a study investigator of laboratory-supported probable, probable, or definite ALS, according to a modified El Escorial criterion (Appendix 2).
2. 21 to 80 years of age inclusive.
3. If patients are taking riluzole for ALS, they must be on a stable dose for at least thirty days prior to the baseline visit.
4. Willing and able to give signed informed consent that has been approved by the Institutional Review Board (IRB).

Exclusion Criteria:

1. Diagnosis of other neurodegenerative diseases (Parkinson disease, Alzheimer disease, etc.).
2. Clinically significant history of unstable medical illness (unstable angina, advanced cancer, etc.) over the last 30 days.
3. Infection with the human immunodeficiency virus (HIV)
4. Limited mental capacity such that the patient cannot provide written informed consent or comply with evaluation procedures.
5. History of recent alcohol or drug abuse or noncompliance with treatment or other experimental protocols. 6 Receipt of any investigational drug within the past 30 days.

Primary outcomes:
measure: Measurement of serum NfL
timeFrame: 12 months
Secondary outcomes:
measure: Measurement of functional decline in ALS
timeFrame: 12 months
measure: Frequency of serious adverse events and adverse events.
timeFrame: 12 months
measure: Survival analysis
timeFrame: 12 months
Other outcomes:
measure: Change in serum CK level from baseline to 12 months
timeFrame: 12 months
Locations:
city: Dallas
country: United States
facility: VA North Texas Health Care System
state: Texas
Study officials:
affiliation: Dallas VA Medical Center
name: Olaf Stuve, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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