Not provided
Not provided
Not provided
Not provided
Study was terminated by the IRB due to continued noncompliance.
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| Brain Chemistry Labs | OTHER |
Not provided
Not provided
Not provided
Not provided
The purpose of this study is to determine the tolerability of L-Serine oral doses for ALS patients and assess preliminary indications of efficacy
All patients will receive the same dose of the study treatment over 6 months. For each participant the study will last approximately one year with follow up visits after the treatment period of 6 months is completed. The visits will include blood draws, vital sign checks, neurological and physical exams, pulmonary testing with forced vital capacity (FVC), and questionnaires.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| L-Serine | Experimental | L-Serine 15 grams orally twice a day as tolerated for 6 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| L-Serine | Drug | L-Serine is a naturally occurring dietary amino acid. It is abundant in soy products, some edible seaweeds, sweet potatoes, eggs and meat. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Dose Tolerability Based on Subject Reporting | Tolerability was based off of participant self-reported GI symptoms at any time during their participation. | From baseline through when participants withdrew from study or up to 48 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Mean ALS Functional Rating Scale - Revised (ALSFRS-R) Score | 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. |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Elijah W Stommel, MD,PHD | Dartmouth-Htichcock Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Dartmouth-Hitchcock Medical Center | Lebanon | New Hampshire | 03756 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25286015 | Background | Abe K, Itoyama Y, Sobue G, Tsuji S, Aoki M, Doyu M, Hamada C, Kondo K, Yoneoka T, Akimoto M, Yoshino H; Edaravone ALS Study Group. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients. Amyotroph Lateral Scler Frontotemporal Degener. 2014 Dec;15(7-8):610-7. doi: 10.3109/21678421.2014.959024. Epub 2014 Oct 6. | |
| 28122372 |
Not provided
Not provided
Not provided
Routine monitoring revealed major noncompliance that was not adequately addressed by the Sponsor-Investigator. Subsequently, the study was terminated by the Institutional Review Board (IRB). The IRB determined these deviations compromised the integrity of the data. Furthermore, the study data collected have been deemed unreliable due to issues related to the study's conduct.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | L-Serine | Participants who provided consent. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Participants determined to be eligible at screening visit
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | L-Serine | Participants determined to be eligible at screening visit |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Customized | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Dose Tolerability Based on Subject Reporting | Tolerability was based off of participant self-reported GI symptoms at any time during their participation. | Routine monitoring revealed major noncompliance that was not adequately addressed by the Sponsor-Investigator. Subsequently, the study was terminated by the Institutional Review Board (IRB). The IRB determined these deviations compromised the integrity of the data. Furthermore, the study data collected have been deemed unreliable due to issues related to the study's conduct. | Posted | Count of Participants | Participants | From baseline through when participants withdrew from study or up to 48 weeks |
|
The adverse event data was collected from baseline through when participants withdrew from study or up to 48 weeks.
Routine monitoring revealed major noncompliance that was not adequately addressed by the Sponsor-Investigator. Subsequently, the study was terminated by the Institutional Review Board (IRB). The IRB determined these deviations compromised the integrity of the data. Furthermore, the study data collected have been deemed unreliable due to issues related to the study's conduct.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | L-Serine | Participants determined to be eligible at screening visit | 1 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Respiratory Arrest | Cardiac disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Falls | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
Routine monitoring revealed major noncompliance that was not adequately addressed by the Sponsor-Investigator. Subsequently, the study was terminated by the Institutional Review Board (IRB). The IRB determined these deviations compromised the integrity of the data. Furthermore, the study data collected have been deemed unreliable due to issues related to the study's conduct.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Elijah Stommel | Dartmouth-Hitchcock Medical Center | 6036505104 | elijah.w.stommel@hitchcock.org |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Dec 7, 2021 | May 31, 2024 | Prot_SAP_000.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
Not provided
Not provided
| ID | Term |
|---|---|
| D012694 | Serine |
| ID | Term |
|---|---|
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
Not provided
Not provided
Not provided
Not provided
Not provided
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Not provided
| Baseline through 12 weeks |
| Efficacy Based on Pulmonary Forced Vital Capacity (FVC) as Measured by Mean Slope Through Time | No data available |
| Background |
| Andrew AS, Caller TA, Tandan R, Duell EJ, Henegan PL, Field NC, Bradley WG, Stommel EW. Environmental and Occupational Exposures and Amyotrophic Lateral Sclerosis in New England. Neurodegener Dis. 2017;17(2-3):110-116. doi: 10.1159/000453359. Epub 2017 Jan 26. |
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| 16457975 | Background | 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. |
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| 24086518 | Background | Dunlop RA, Cox PA, Banack SA, Rodgers KJ. The non-protein amino acid BMAA is misincorporated into human proteins in place of L-serine causing protein misfolding and aggregation. PLoS One. 2013 Sep 25;8(9):e75376. doi: 10.1371/journal.pone.0075376. eCollection 2013. |
| 29098664 | Background | Dunlop RA, Powell J, Guillemin GJ, Cox PA. Mechanisms of L-Serine Neuroprotection in vitro Include ER Proteostasis Regulation. Neurotox Res. 2018 Jan;33(1):123-132. doi: 10.1007/s12640-017-9829-3. Epub 2017 Nov 2. |
| 28975502 | Background | Dunlop RA, Powell JT, Metcalf JS, Guillemin GJ, Cox PA. L-Serine-Mediated Neuroprotection Includes the Upregulation of the ER Stress Chaperone Protein Disulfide Isomerase (PDI). Neurotox Res. 2018 Jan;33(1):113-122. doi: 10.1007/s12640-017-9817-7. Epub 2017 Oct 3. |
| 25130657 | Background | Fiandaca MS, Kapogiannis D, Mapstone M, Boxer A, Eitan E, Schwartz JB, Abner EL, Petersen RC, Federoff HJ, Miller BL, Goetzl EJ. Identification of preclinical Alzheimer's disease by a profile of pathogenic proteins in neurally derived blood exosomes: A case-control study. Alzheimers Dement. 2015 Jun;11(6):600-7.e1. doi: 10.1016/j.jalz.2014.06.008. Epub 2014 Aug 15. |
| 22045570 | Background | Garofalo K, Penno A, Schmidt BP, Lee HJ, Frosch MP, von Eckardstein A, Brown RH, Hornemann T, Eichler FS. Oral L-serine supplementation reduces production of neurotoxic deoxysphingolipids in mice and humans with hereditary sensory autonomic neuropathy type 1. J Clin Invest. 2011 Dec;121(12):4735-45. doi: 10.1172/JCI57549. |
| 26062630 | Background | Goetzl EJ, Boxer A, Schwartz JB, Abner EL, Petersen RC, Miller BL, Kapogiannis D. Altered lysosomal proteins in neural-derived plasma exosomes in preclinical Alzheimer disease. Neurology. 2015 Jul 7;85(1):40-7. doi: 10.1212/WNL.0000000000001702. Epub 2015 Jun 10. |
| 17261678 | Background | 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. |
| 18372902 | Background | Kabashi E, Valdmanis PN, Dion P, Spiegelman D, McConkey BJ, Vande Velde C, Bouchard JP, Lacomblez L, Pochigaeva K, Salachas F, Pradat PF, Camu W, Meininger V, Dupre N, Rouleau GA. TARDBP mutations in individuals with sporadic and familial amyotrophic lateral sclerosis. Nat Genet. 2008 May;40(5):572-4. doi: 10.1038/ng.132. Epub 2008 Mar 30. |
| 15642901 | Background | 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. |
| 19710046 | Background | 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. |
| 27490513 | Background | Mehta P, Kaye W, Bryan L, Larson T, Copeland T, Wu J, Muravov O, Horton K. Prevalence of Amyotrophic Lateral Sclerosis - United States, 2012-2013. MMWR Surveill Summ. 2016 Aug 5;65(8):1-12. doi: 10.15585/mmwr.ss6508a1. |
| 28929385 | Background | 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. |
| 28620737 | Background | Metcalf JS, Lobner D, Banack SA, Cox GA, Nunn PB, Wyatt PB, Cox PA. Analysis of BMAA enantiomers in cycads, cyanobacteria, and mammals: in vivo formation and toxicity of D-BMAA. Amino Acids. 2017 Aug;49(8):1427-1439. doi: 10.1007/s00726-017-2445-y. Epub 2017 Jun 15. |
| 15295100 | Background | 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. |
| 21836033 | Background | Phukan J, Elamin M, Bede P, Jordan N, Gallagher L, Byrne S, Lynch C, Pender N, Hardiman O. The syndrome of cognitive impairment in amyotrophic lateral sclerosis: a population-based study. J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):102-8. doi: 10.1136/jnnp-2011-300188. Epub 2011 Aug 11. |
| 18362273 | Background | Polman CH, Reingold SC, Barkhof F, Calabresi PA, Clanet M, Cohen JA, Cutter GR, Freedman MS, Kappos L, Lublin FD, McFarland HF, Metz LM, Miller AE, Montalban X, O'Connor PW, Panitch H, Richert JR, Petkau J, Schwid SR, Sormani MP, Thompson AJ, Weinshenker BG, Wolinsky JS. Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment. Neurology. 2008 Mar 25;70(13 Pt 2):1134-40. doi: 10.1212/01.wnl.0000306410.84794.4d. |
| 16116120 | Background | 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. |
| 14986774 | Background | 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. |
| 7746977 | Background | 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. |
| 27174238 | Background | 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. |
| 23913901 | Background | 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. |
| 17909153 | Background | 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. |
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| 27589995 | Background | Levine TD, Miller RG, Bradley WG, Moore DH, Saperstein DS, Flynn LE, Katz JS, Forshew DA, Metcalf JS, Banack SA, Cox PA. Phase I clinical trial of safety of L-serine for ALS patients. Amyotroph Lateral Scler Frontotemporal Degener. 2017 Feb;18(1-2):107-111. doi: 10.1080/21678421.2016.1221971. Epub 2016 Sep 2. |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Secondary | Mean ALS Functional Rating Scale - Revised (ALSFRS-R) Score | 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. | Routine monitoring revealed major noncompliance that was not adequately addressed by the Sponsor-Investigator. Subsequently, the study was terminated by the Institutional Review Board (IRB). The IRB determined these deviations compromised the integrity of the data. Furthermore, the study data collected have been deemed unreliable due to issues related to the study's conduct. | Posted | Mean | Standard Deviation | Mean score | Baseline through 12 weeks |
|
|
|
| Secondary | Efficacy Based on Pulmonary Forced Vital Capacity (FVC) as Measured by Mean Slope Through Time | Routine monitoring revealed major noncompliance that was not adequately addressed by the Sponsor-Investigator. Subsequently, study was terminated by the Institutional Review Board. The protocol specified that this outcome measure would obtain the slope through time as a measure of efficacy based on FVC. Although raw data for the FVC was collected, these data were not analyzed and slope values were not obtained before study closure. The slope values will never be obtained due to study termination | Posted | No data available |
|
|
| 37 |
| 12 |
| 37 |
| 31 |
| 37 |
| Bowel Obstruction | Gastrointestinal disorders | Non-systematic Assessment |
|
| Viral infection and mild rhabdomyolysis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Suicide Attempt | Psychiatric disorders | Non-systematic Assessment |
|
| Breathing difficulty/Ventilation Issues | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Gastric tube Placement | Surgical and medical procedures | Non-systematic Assessment |
|
| Pre-Planned Surgical Procedure | Surgical and medical procedures | Non-systematic Assessment |
|
| Worsening weakness and Falls | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Bimalleolar Fracture with Lateral Subluxation | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
Not provided
Not provided
Not provided
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |