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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04244630
Other study ID # 19-094
Secondary ID
Status Recruiting
Phase Phase 2
First received
Last updated
Start date April 1, 2022
Est. completion date December 2023

Study information

Verified date March 2022
Source Dallas VA Medical Center
Contact Rehana Hussain, M.Sc.
Phone 214-648-7244
Email rehana.hussain@utsouthwestern.edu
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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


Recruitment information / eligibility

Status Recruiting
Enrollment 60
Est. completion date December 2023
Est. primary completion date December 2023
Accepts healthy volunteers No
Gender All
Age group 21 Years to 80 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Combination Product:
Antioxidants
Over-the-counter anti-oxidants, namely vitamin E, NAc cysteine, L-cystine, Nicotinamide and Taurursodiol at defined doses

Locations

Country Name City State
United States VA North Texas Health Care System Dallas Texas

Sponsors (1)

Lead Sponsor Collaborator
Dallas VA Medical Center

Country where clinical trial is conducted

United States, 

References & Publications (32)

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Brooks BR. El Escorial World Federation of Neurology criteria for the diagnosis of amyotrophic lateral sclerosis. Subcommittee on Motor Neuron Diseases/Amyotrophic Lateral Sclerosis of the World Federation of Neurology Research Group on Neuromuscular Diseases and the El Escorial "Clinical limits of amyotrophic lateral sclerosis" workshop contributors. J Neurol Sci. 1994 Jul;124 Suppl:96-107. — View Citation

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Huisman MH, de Jong SW, van Doormaal PT, Weinreich SS, Schelhaas HJ, van der Kooi AJ, de Visser M, Veldink JH, van den Berg LH. Population based epidemiology of amyotrophic lateral sclerosis using capture-recapture methodology. J Neurol Neurosurg Psychiatry. 2011 Oct;82(10):1165-70. doi: 10.1136/jnnp.2011.244939. Epub 2011 May 27. — View Citation

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Lu CH, Macdonald-Wallis C, Gray E, Pearce N, Petzold A, Norgren N, Giovannoni G, Fratta P, Sidle K, Fish M, Orrell R, Howard R, Talbot K, Greensmith L, Kuhle J, Turner MR, Malaspina A. Neurofilament light chain: A prognostic biomarker in amyotrophic lateral sclerosis. Neurology. 2015 Jun 2;84(22):2247-57. doi: 10.1212/WNL.0000000000001642. Epub 2015 May 1. Erratum in: Neurology. 2015 Sep 8;85(10):921. — View Citation

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Taylor JP, Brown RH Jr, Cleveland DW. Decoding ALS: from genes to mechanism. Nature. 2016 Nov 10;539(7628):197-206. doi: 10.1038/nature20413. Review. — View Citation

Thouvenot E, Demattei C, Lehmann S, Maceski-Maleska A, Hirtz C, Juntas-Morales R, Pageot N, Esselin F, Alphandéry S, Vincent T, Camu W. Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis. Eur J Neurol. 2020 Feb;27(2):251-257. doi: 10.1111/ene.14063. Epub 2019 Sep 18. — View Citation

van Es MA, Hardiman O, Chio A, Al-Chalabi A, Pasterkamp RJ, Veldink JH, van den Berg LH. Amyotrophic lateral sclerosis. Lancet. 2017 Nov 4;390(10107):2084-2098. doi: 10.1016/S0140-6736(17)31287-4. Epub 2017 May 25. Review. — View Citation

Verde F, Steinacker P, Weishaupt JH, Kassubek J, Oeckl P, Halbgebauer S, Tumani H, von Arnim CAF, Dorst J, Feneberg E, Mayer B, Müller HP, Gorges M, Rosenbohm A, Volk AE, Silani V, Ludolph AC, Otto M. Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry. 2019 Feb;90(2):157-164. doi: 10.1136/jnnp-2018-318704. Epub 2018 Oct 11. — View Citation

Wang G, Han T, Nijhawan D, Theodoropoulos P, Naidoo J, Yadavalli S, Mirzaei H, Pieper AA, Ready JM, McKnight SL. P7C3 neuroprotective chemicals function by activating the rate-limiting enzyme in NAD salvage. Cell. 2014 Sep 11;158(6):1324-1334. doi: 10.1016/j.cell.2014.07.040. — View Citation

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* Note: There are 32 references in allClick here to view all references

Outcome

Type Measure Description Time frame Safety issue
Other Change in serum CK level from baseline to 12 months CK levels will be measured in a clinical laboratory by colorimetric measurements. Analysis of serum CK levels will be conducted similar to serum NfL. 12 months
Primary Measurement of serum NfL The change in log serum NfL level from baseline to 12 months will be assessed using a linear mixed model and the differences in NfL level at 12 months from baseline assessed using a paired t-test. 12 months
Secondary Measurement of functional decline in ALS Functional decline in ALS patients will be measured using the ALS Functional Rating Scale - Revised (ALSFRS-R), change will be measured from baseline to 12 months.
The ALSFRS-R is a quickly administered (five minutes) ordinal rating scale that assesses patients' capability and independence in 12 functional activities.
12 months
Secondary Frequency of serious adverse events and adverse events. The frequency of serious adverse events and adverse events will be summarized using frequency and percentages. 12 months
Secondary Survival analysis This is a robust measure of effect in this rapidly progressing terminal disease. Survival has been a standard outcome measure in past clinical trials. 12 months
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