Study Summary
This trial is testing a new ALS treatment to see if it is safe and effective.
Eligible Conditions
- Lou Gehrig's Disease
Treatment Effectiveness
Phase-Based Effectiveness
Phase 2
Study Objectives
1 Primary · 3 Secondary · Reporting Duration: Baseline, 1 year
6 months
Dose tolerability based on subject reporting
Baseline, 1 year
Efficacy based on ALS Functional Rating Scale - Revised (ALSFRS-R)
Baseline, 6 months
Efficacy based on neurological exam
Efficacy based on pulmonary forced vital capacity
Trial Safety
Phase-Based Safety
This is further along than 68% of similar trials
Awards & Highlights
No Placebo Group
All patients enrolled in this trial will receive the new treatment.
Trial Design
1 Treatment Group
L-Serine
1 of 1
Experimental Treatment
43 Total Participants · 1 Treatment Group
Primary Treatment: L-Serine · No Placebo Group · Phase 2
L-Serine
Drug
Experimental Group · 1 Intervention: L-Serine · Intervention Types: DrugTrial Logistics
Trial Timeline
Screening: ~3 weeks
Treatment: Varies
Reporting: baseline, 1 year
Who is running the clinical trial?
Elijah W. StommelLead Sponsor
Brain Chemistry Labs, Institute for EthnomedicineUNKNOWN
1 Previous Clinical Trials
40 Total Patients Enrolled
Elijah W Stommel, MD,PHDPrincipal InvestigatorDartmouth-Htichcock Medical Center
Eligibility Criteria
Age 18+ · All Participants · 3 Total Inclusion Criteria
Mark “Yes” if the following statements are true for you:References
- Garofalo, Kevin, Anke Penno, Brian P. Schmidt, Ho-Joon Lee, Matthew P. Frosch, Arnold von Eckardstein, Robert H. Brown, Thorsten Hornemann, and Florian S. Eichler. 2011. “Oral L-serine Supplementation Reduces Production of Neurotoxic Deoxysphingolipids in Mice and Humans with Hereditary Sensory Autonomic Neuropathy Type 1”. Journal of Clinical Investigation. American Society for Clinical Investigation. doi:10.1172/jci57549.
- Phukan, Julie, Marwa Elamin, Peter Bede, Norah Jordan, Laura Gallagher, Susan Byrne, Catherine Lynch, Niall Pender, and Orla Hardiman. 2011. “The Syndrome of Cognitive Impairment in Amyotrophic Lateral Sclerosis: A Population-based Study”. Journal of Neurology, Neurosurgery & Psychiatry. BMJ. doi:10.1136/jnnp-2011-300188.
- Brannath, Werner, Hans Ulrich Burger, Ekkehard Glimm, Nigel Stallard, Marc Vandemeulebroecke, and Gernot Wassmer. 2010. “Comments on the Draft Guidance on “adaptive Design Clinical Trials for Drugs and Biologics” of the U.S. Food and Drug Administration”. Journal of Biopharmaceutical Statistics. Informa UK Limited. doi:10.1080/10543406.2010.514453.
- Kaufmann, P., G. Levy, J. L.P. Thompson, M. L. DelBene, V. Battista, P. H. Gordon, L. P. Rowland, B. Levin, and H. Mitsumoto. 2005. “The Alsfrsr Predicts Survival Time in an ALS Clinic Population”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/01.wnl.0000148648.38313.64.
- Cedarbaum, Jesse M., Nancy Stambler, Errol Malta, Cynthia Fuller, Dana Hilt, Barbara Thurmond, and Arline Nakanishi. 1999. “The ALSFRS-R: A Revised ALS Functional Rating Scale That Incorporates Assessments of Respiratory Function”. Journal of the Neurological Sciences. Elsevier BV. doi:10.1016/s0022-510x(99)00210-5.
- Goetzl, Edward J., Adam Boxer, Janice B. Schwartz, Erin L. Abner, Ronald C. Petersen, Bruce L. Miller, and Dimitrios Kapogiannis. 2015. “Altered Lysosomal Proteins in Neural-derived Plasma Exosomes in Preclinical Alzheimer Disease”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/wnl.0000000000001702.
- Ringholz, G. M., S. H. Appel, M. Bradshaw, N. A. Cooke, D. M. Mosnik, and P. E. Schulz. 2005. “Prevalence and Patterns of Cognitive Impairment in Sporadic ALS”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/01.wnl.0000172911.39167.b6.
- Spławiński, Jacek, and Jerzy Kuźniar. 2004. “Clinical Trials: Active Control Vs Placebo — What Is Ethical?”. Science and Engineering Ethics. Springer Science and Business Media LLC. doi:10.1007/s11948-004-0065-x.
- Thall, Peter F., Richard M. Simon, and Elihu H. Estey. 1995. “Bayesian Sequential Monitoring Designs for Single-arm Clinical Trials with Multiple Outcomes”. Statistics in Medicine. Wiley. doi:10.1002/sim.4780140404.
- Wheaton, M. W., A. R. Salamone, D. M. Mosnik, R. O. McDonald, S. H. Appel, H. I. Schmolck, G. M. Ringholz, and P. E. Schulz. 2007. “Cognitive Impairment in Familial ALS”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/01.wnl.0000277422.11236.2c.
- Winston, Charisse N., Edward J. Goetzl, Johnny C. Akers, Bob S. Carter, Edward M. Rockenstein, Douglas Galasko, Eliezer Masliah, and Robert A. Rissman. 2016. “Prediction of Conversion from Mild Cognitive Impairment to Dementia with Neuronally Derived Blood Exosome Protein Profile”. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring. Wiley. doi:10.1016/j.dadm.2016.04.001.
- Brooks, Benjamin Rix, Robert G Miller, Michael Swash, and Theodore L Munsat. 2000. “El Escorial Revisited: Revised Criteria for the Diagnosis of Amyotrophic Lateral Sclerosis”. Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders. Informa UK Limited. doi:10.1080/146608200300079536.
- Abe, Koji, Yasuto Itoyama, Gen Sobue, Shoji Tsuji, Masashi Aoki, Manabu Doyu, Chikuma Hamada, et al.. 2014. “Confirmatory Double-blind, Parallel-group, Placebo-controlled Study of Efficacy and Safety of Edaravone (MCI-186) in Amyotrophic Lateral Sclerosis Patients”. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Informa UK Limited. doi:10.3109/21678421.2014.959024.
- Canu, Nadia, Maria Teresa Ciotti, and Loredano Pollegioni. 2014. “Serine Racemase: A Key Player in Apoptosis and Necrosis”. Frontiers in Synaptic Neuroscience. Frontiers Media SA. doi:10.3389/fnsyn.2014.00009.
- Cox, Paul Alan, Sandra Anne Banack, and Susan J. Murch. 2003. “Biomagnification of Cyanobacterial Neurotoxins and Neurodegenerative Disease Among the Chamorro People of Guam”. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.2235808100.
- Cox, Paul Alan, David A. Davis, Deborah C. Mash, James S. Metcalf, and Sandra Anne Banack. 2016. “Dietary Exposure to an Environmental Toxin Triggers Neurofibrillary Tangles and Amyloid Deposits in the Brain”. Proceedings of the Royal Society B: Biological Sciences. The Royal Society. doi:10.1098/rspb.2015.2397.
- Hirtz, D., D. J. Thurman, K. Gwinn-Hardy, M. Mohamed, A. R. Chaudhuri, and R. Zalutsky. 2007. “How Common Are the "common" Neurologic Disorders?”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/01.wnl.0000252807.38124.a3.
- Mehta, Paul, Wendy Kaye, Leah Bryan, Theodore Larson, Timothy Copeland,, Jennifer Wu, Oleg Muravov, and Kevin Horton. 2016. “Prevalence of Amyotrophic Lateral Sclerosis — United States, 2012–2013”. MMWR. Surveillance Summaries. Centers for Disease Control MMWR Office. doi:10.15585/mmwr.ss6508a1.
- Thompson, Alexander G., Elizabeth Gray, Sabrina M. Heman-Ackah, Imre Mäger, Kevin Talbot, Samir El Andaloussi, Matthew J. Wood, and Martin R. Turner. 2016. “Extracellular Vesicles in Neurodegenerative Disease — Pathogenesis to Biomarkers”. Nature Reviews Neurology. Springer Science and Business Media LLC. doi:10.1038/nrneurol.2016.68.
- Andrew, Angeline S., Tracie A. Caller, Rup Tandan, Eric J. Duell, Patricia L. Henegan, Nicholas C. Field, Walter G. Bradley, and Elijah W. Stommel. 2017. “Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England”. Neurodegenerative Diseases. S. Karger AG. doi:10.1159/000453359.
- Dunlop, R. A., J. Powell, G. J. Guillemin, and P. A. Cox. 2017. “Mechanisms of L-serine Neuroprotection in Vitro Include ER Proteostasis Regulation”. Neurotoxicity Research. Springer Science and Business Media LLC. doi:10.1007/s12640-017-9829-3.
- Metcalf, J. S., R. A. Dunlop, J. T. Powell, S. A. Banack, and P. A. Cox. 2017. “L-serine: A Naturally-occurring Amino Acid with Therapeutic Potential”. Neurotoxicity Research. Springer Science and Business Media LLC. doi:10.1007/s12640-017-9814-x.
- Metcalf, J. S., Doug Lobner, Sandra Anne Banack, Gregory A. Cox, Peter B. Nunn, Peter B. Wyatt, and Paul Alan Cox. 2017. “Analysis of BMAA Enantiomers in Cycads, Cyanobacteria, and Mammals: In Vivo Formation and Toxicity of D-bmaa”. Amino Acids. Springer Science and Business Media LLC. doi:10.1007/s00726-017-2445-y.
- Levine, Todd D., Robert G. Miller, Walter G. Bradley, Dan H. Moore, David S. Saperstein, Lynne E. Flynn, Jonathan S. Katz, et al.. 2016. “Phase I Clinical Trial of Safety of L-serine for ALS Patients”. Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration. Informa UK Limited. doi:10.1080/21678421.2016.1221971.
- Banack, Sandra Anne, Susan J. Murch, and Paul Alan Cox. 2006. “Neurotoxic Flying Foxes as Dietary Items for the Chamorro People, Marianas Islands”. Journal of Ethnopharmacology. Elsevier BV. doi:10.1016/j.jep.2005.12.032.
- Caller, Tracie A., Angeline Andrews, Nicholas C. Field, Patricia L. Henegan, and Elijah W. Stommel. 2015. “The Epidemiology of Amyotrophic Lateral Sclerosis in New Hampshire, USA, 2004-2007”. Neurodegenerative Diseases. S. Karger AG. doi:10.1159/000374117.
- de Koning, T. J.. 2005. “Treatment with Amino Acids in Serine Deficiency Disorders”. Journal of Inherited Metabolic Disease. Wiley. doi:10.1007/s10545-006-0269-0.
- Dunlop, R. A., J. T. Powell, J. S. Metcalf, G. J. Guillemin, and P. A. Cox. 2017. “L-serine-mediated Neuroprotection Includes the Upregulation of the ER Stress Chaperone Protein Disulfide Isomerase (PDI)”. Neurotoxicity Research. Springer Science and Business Media LLC. doi:10.1007/s12640-017-9817-7.
- Braak, Heiko, and Eva Braak. 1995. “Staging of Alzheimer's Disease-related Neurofibrillary Changes”. Neurobiology of Aging. Elsevier BV. doi:10.1016/0197-4580(95)00021-6.
- Fiandaca, Massimo S., Dimitrios Kapogiannis, Mark Mapstone, Adam Boxer, Erez Eitan, Janice B. Schwartz, Erin L. Abner, et al.. 2014. “Identification of Preclinical Alzheimer's Disease by a Profile of Pathogenic Proteins in Neurally Derived Blood Exosomes: A Case‐control Study”. Alzheimer's & Dementia. Wiley. doi:10.1016/j.jalz.2014.06.008.
- Kabashi, Edor, Paul N Valdmanis, Patrick Dion, Dan Spiegelman, Brendan J McConkey, Christine Vande Velde, Jean-Pierre Bouchard, et al.. 2008. “TARDBP Mutations in Individuals with Sporadic and Familial Amyotrophic Lateral Sclerosis”. Nature Genetics. Springer Science and Business Media LLC. doi:10.1038/ng.132.
- Logroscino, G., B. J Traynor, O. Hardiman, A. Chio, D. Mitchell, R. J Swingler, A. Millul, E. Benn, E. Beghi, and for EURALS. 2009. “Incidence of Amyotrophic Lateral Sclerosis in Europe”. Journal of Neurology, Neurosurgery & Psychiatry. BMJ. doi:10.1136/jnnp.2009.183525.
- Polman, C. H., S. C. Reingold, F. Barkhof, P. A. Calabresi, M. Clanet, J. A. Cohen, G. R. Cutter, et al.. 2008. “Ethics of Placebo-controlled Clinical Trials in Multiple Sclerosis: A Reassessment”. Neurology. Ovid Technologies (Wolters Kluwer Health). doi:10.1212/01.wnl.0000306410.84794.4d.
- Viele, Kert, Scott Berry, Beat Neuenschwander, Billy Amzal, Fang Chen, Nathan Enas, Brian Hobbs, et al.. 2013. “Use of Historical Control Data for Assessing Treatment Effects in Clinical Trials”. Pharmaceutical Statistics. Wiley. doi:10.1002/pst.1589.
- Desai, J. R., E. A. Bowen, M. M. Danielson, R. R. Allam, and M. N. Cantor. 2013. “Creation and Implementation of a Historical Controls Database from Randomized Clinical Trials”. Journal of the American Medical Informatics Association. Oxford University Press (OUP). doi:10.1136/amiajnl-2012-001257.
- Dunlop, Rachael Anne, Paul Alan Cox, Sandra Anne Banack, and Kenneth John Rodgers. 2013. “The Non-protein Amino Acid BMAA Is Misincorporated into Human Proteins in Place of L-serine Causing Protein Misfolding and Aggregation”. Edited by Gilles J. Guillemin. Plos ONE. Public Library of Science (PLoS). doi:10.1371/journal.pone.0075376.
- Murch, Susan J., Paul Alan Cox, and Sandra Anne Banack. 2004. “A Mechanism for Slow Release of Biomagnified Cyanobacterial Neurotoxins and Neurodegenerative Disease in Guam”. Proceedings of the National Academy of Sciences. Proceedings of the National Academy of Sciences. doi:10.1073/pnas.0404926101.
- Cedarbaum JM, Stambler N, Malta E, Fuller C, Hilt D, Thurmond B, Nakanishi A. The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. BDNF ALS Study Group (Phase III). J Neurol Sci. 1999 Oct 31;169(1-2):13-21. doi: 10.1016/s0022-510x(99)00210-5.
- Kaufmann P, Levy G, Thompson JL, Delbene ML, Battista V, Gordon PH, Rowland LP, Levin B, Mitsumoto H. The ALSFRSr predicts survival time in an ALS clinic population. Neurology. 2005 Jan 11;64(1):38-43. doi: 10.1212/01.WNL.0000148648.38313.64.
- Thall PF, Simon RM, Estey EH. Bayesian sequential monitoring designs for single-arm clinical trials with multiple outcomes. Stat Med. 1995 Feb 28;14(4):357-79. doi: 10.1002/sim.4780140404.
- Brooks BR, Miller RG, Swash M, Munsat TL; World Federation of Neurology Research Group on Motor Neuron Diseases. El Escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler Other Motor Neuron Disord. 2000 Dec;1(5):293-9. doi: 10.1080/146608200300079536. No abstract available.
- Cox PA, Banack SA, Murch SJ. Biomagnification of cyanobacterial neurotoxins and neurodegenerative disease among the Chamorro people of Guam. Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13380-3. doi: 10.1073/pnas.2235808100.
- Hirtz D, Thurman DJ, Gwinn-Hardy K, Mohamed M, Chaudhuri AR, Zalutsky R. How common are the "common" neurologic disorders? Neurology. 2007 Jan 30;68(5):326-37. doi: 10.1212/01.wnl.0000252807.38124.a3.
- Ringholz GM, Appel SH, Bradshaw M, Cooke NA, Mosnik DM, Schulz PE. Prevalence and patterns of cognitive impairment in sporadic ALS. Neurology. 2005 Aug 23;65(4):586-90. doi: 10.1212/01.wnl.0000172911.39167.b6.
- Cox PA, Davis DA, Mash DC, Metcalf JS, Banack SA. Dietary exposure to an environmental toxin triggers neurofibrillary tangles and amyloid deposits in the brain. Proc Biol Sci. 2016 Jan 27;283(1823):20152397. doi: 10.1098/rspb.2015.2397.
- de Koning TJ. Treatment with amino acids in serine deficiency disorders. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):347-51. doi: 10.1007/s10545-006-0269-0.
- Murch SJ, Cox PA, Banack SA. A mechanism for slow release of biomagnified cyanobacterial neurotoxins and neurodegenerative disease in Guam. Proc Natl Acad Sci U S A. 2004 Aug 17;101(33):12228-31. doi: 10.1073/pnas.0404926101. Epub 2004 Aug 4.
- Viele K, Berry S, Neuenschwander B, Amzal B, Chen F, Enas N, Hobbs B, Ibrahim JG, Kinnersley N, Lindborg S, Micallef S, Roychoudhury S, Thompson L. Use of historical control data for assessing treatment effects in clinical trials. Pharm Stat. 2014 Jan-Feb;13(1):41-54. doi: 10.1002/pst.1589. Epub 2013 Aug 5.
- Splawinski J, Kuzniar J. Clinical trials: active control vs placebo--what is ethical? Sci Eng Ethics. 2004 Jan;10(1):73-9. doi: 10.1007/s11948-004-0065-x.
- Braak H, Braak E. Staging of Alzheimer's disease-related neurofibrillary changes. Neurobiol Aging. 1995 May-Jun;16(3):271-8; discussion 278-84. doi: 10.1016/0197-4580(95)00021-6.
- Banack SA, Murch SJ, Cox PA. Neurotoxic flying foxes as dietary items for the Chamorro people, Marianas Islands. J Ethnopharmacol. 2006 Jun 15;106(1):97-104. doi: 10.1016/j.jep.2005.12.032. Epub 2006 Feb 7.
- Logroscino G, Traynor BJ, Hardiman O, Chio A, Mitchell D, Swingler RJ, Millul A, Benn E, Beghi E; EURALS. Incidence of amyotrophic lateral sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2010 Apr;81(4):385-90. doi: 10.1136/jnnp.2009.183525. Epub 2009 Aug 25.
- Metcalf JS, Dunlop RA, Powell JT, Banack SA, Cox PA. L-Serine: a Naturally-Occurring Amino Acid with Therapeutic Potential. Neurotox Res. 2018 Jan;33(1):213-221. doi: 10.1007/s12640-017-9814-x. Epub 2017 Sep 19.
- Canu N, Ciotti MT, Pollegioni L. Serine racemase: a key player in apoptosis and necrosis. Front Synaptic Neurosci. 2014 Apr 21;6:9. doi: 10.3389/fnsyn.2014.00009. eCollection 2014.
- Thompson AG, Gray E, Heman-Ackah SM, Mager I, Talbot K, Andaloussi SE, Wood MJ, Turner MR. Extracellular vesicles in neurodegenerative disease - pathogenesis to biomarkers. Nat Rev Neurol. 2016 Jun;12(6):346-57. doi: 10.1038/nrneurol.2016.68. Epub 2016 May 13.
- Wheaton MW, Salamone AR, Mosnik DM, McDonald RO, Appel SH, Schmolck HI, Ringholz GM, Schulz PE. Cognitive impairment in familial ALS. Neurology. 2007 Oct 2;69(14):1411-7. doi: 10.1212/01.wnl.0000277422.11236.2c.
- Elijah W. Stommel 2018. "Tolerability and Efficacy of L-Serine in Patients With Amyotrophic Lateral Sclerosis (ALS)". ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03580616.
Frequently Asked Questions
What maladies has L-Serine been found to alleviate?
"L-Serine has proven to be an efficacious therapy when treating iron deficiency and supplementing amino acid deficiencies." - Anonymous Online Contributor
Unverified Answer
Has the FDA sanctioned L-Serine for therapeutic applications?
"Our team at Power has evaluated the safety of L-Serine and assigned it a score of 2 due to evidence from Phase 2 trials that suggest its harmlessness, yet lack any proof for effectiveness." - Anonymous Online Contributor
Unverified Answer
What is the current cohort size of this clinical trial?
"Affirmative. The information on clinicaltrials.gov suggests that enrollment for this trial is ongoing - the study was established on October 24th 2018 and the details were last updated on February 22nd 2022. At present, they are seeking 50 participants from one location." - Anonymous Online Contributor
Unverified Answer
Could you tell me if this clinical experiment is currently seeking participants?
"Affirmative. Data from clinicaltrials.gov shows that this medical trial, which commenced on October 24th 2018, is actively seeking participants for enrolment. 50 patients are needed to be recruited from one location." - Anonymous Online Contributor
Unverified Answer
Has L-Serine been investigated in prior empirical investigations?
"Currently, 4 clinical trials exploring the effects of L-Serine are ongoing with none in their final stages. While Lebanon, New Hampshire has a concentration of these studies, there exists another 5 sites where research is taking place." - Anonymous Online Contributor
Unverified Answer