Ignite Creation Date:
2025-12-25 @ 3:25 AM
Ignite Modification Date:
2025-12-26 @ 2:05 AM
Study NCT ID:
NCT06953505
Status:
ENROLLING_BY_INVITATION
Last Update Posted:
2025-10-06
First Post:
2025-04-16
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
At Home Ammonia Monitoring of Inborn Errors of Ammonia Metabolism
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D056806', 'term': 'Urea Cycle Disorders, Inborn'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}], 'ancestors': [{'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D000592', 'term': 'Amino Acid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2024-08-13', 'size': 169439, 'label': 'Informed Consent Form: Child Assent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_001.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-04-16T12:43', 'hasProtocol': False}, {'date': '2024-08-13', 'size': 215859, 'label': 'Informed Consent Form: Adult Consent Form', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_000.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-04-16T12:42', 'hasProtocol': False}, {'date': '2025-09-23', 'size': 268353, 'label': 'Informed Consent Form: Adult Consent Form - revised 9/23/2025', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_002.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-09-30T17:43', 'hasProtocol': False}, {'date': '2025-09-23', 'size': 211681, 'label': 'Informed Consent Form: Child Assent Form - revised 9/23/2025', 'hasIcf': True, 'hasSap': False, 'filename': 'ICF_003.pdf', 'typeAbbrev': 'ICF', 'uploadDate': '2025-09-30T17:44', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'DEVICE_FEASIBILITY', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 30}}, 'statusModule': {'overallStatus': 'ENROLLING_BY_INVITATION', 'startDateStruct': {'date': '2025-09-23', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-09', 'completionDateStruct': {'date': '2027-08', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-09-30', 'studyFirstSubmitDate': '2025-04-16', 'studyFirstSubmitQcDate': '2025-04-23', 'lastUpdatePostDateStruct': {'date': '2025-10-06', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2025-05-01', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-07', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of daily ammonia measurements completed.', 'timeFrame': 'through individual participant study completion - approximately 240 days per participant with an optional 120 day additional extension period available.', 'description': 'Daily ammonia measurements will be completed on the ammonia study device. A single participant will have a single device. The device will store information about the time, date, and results from the measurements completed. The primary hypothesis is that participants will complete 90% of the daily ammonia measurements during their individual study periods.'}], 'secondaryOutcomes': [{'measure': 'Descriptive Statistics and Correlations', 'timeFrame': 'From enrollment through study completion, this is an average of 240 days per participant. If a participant chooses to participate in the optional study extension then the time frame will be approximately 360 days per participant.', 'description': 'After the study is complete, descriptive statistics (mean, median, range) will be calculated for individual participants for the study for the quantitative home measurements (temperature, heart rate, pulse oxygenation, and capillary ammonia). Descriptive statistics (mean, median, range) will be calculated for all aggregated participant data for the study for the quantitative home measurements (temperature, heart rate, pulse oxygenation, and capillary ammonia). The strength of correlations between quantitative values and participant self reported survey information and/or medical record documented clinical events will be investigated.'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isUnapprovedDevice': True, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'conditions': ['Urea Cycle Disorders', 'Organic Acidemias', 'Fatty Acid Oxidation Disorder', 'Ammonia; Metabolic Disorder']}, 'descriptionModule': {'briefSummary': 'The goal of this observational study is to learn if people with certain ammonia metabolism disorders will measure their ammonia levels at home.\n\nThe main question it aims to answer is:\n\n• Will participants measure their ammonia every day?\n\nParticipants will be asked to:\n\n* Attend three in-person study visits at the clinic.\n* Measure temperature, heart rate, and blood oxygen every day.\n* Complete a short survey every day.\n* Measure ammonia every day.', 'detailedDescription': "Ammonium (NH4+, ion in aqueous solution) exists in equilibrium with ammonia (NH3, gas) according to the equilibrium reaction: NH3+ + H+ ↔ NH4+, which has a pKa of 9.25.\\[1\\] Total ammonia is the sum of all ammonium ions (NH4+) and ammonia gas (NH3) present. At the physiologically relevant pH of blood (\\~7.4), the ammonium/ammonia equilibrium is almost completely shifted to NH4+.\\[2\\] Total ammonia is colloquially referred to as ammonia in clinical medicine and clinical chemistry. Thus, the term ammonia in this document refers to total ammonia unless otherwise specified.\n\nOngoing metabolic processes in the human body continuously generate ammonia.\\[1,3-8\\] Ammonia is produced in all tissues of the body, mainly by the process of transamination followed by deamination, from biogenic amines and amino groups of nitrogenous bases (e.g., purines, pyrimidines), and within the intestine by intestinal bacterial flora through the action of urease on urea.\\[1, 7\\] Much of the ammonia produced in the intestine travels to the liver via the portal circulation. Ammonia produced by the kidneys variably clears the body in urine or enters the systemic circulation via the renal veins.\\[7-9\\]\n\nAmmonia levels within an individual are highly dynamic over the course of a day based on dietary and exercise status.\n\nBecause of the dynamic ongoing metabolic cellular processes that generate and dispose of ammonia, accurate measurement of ammonia can be challenging; cellular components in blood may continue to create ammonia after the blood is drawn, amino acids may deaminate nonenzymatically or enzymatically. Blood samples should be immediately measured. If not immediately measured, then blood samples should be kept on ice and measured within 30 minutes of collection.\n\nAmmonia is toxic to the central nervous system.\\[10\\]\n\nIncreased ammonia within the blood (hyperammonemia) may be caused by a variety of factors, including:\n\nConditions associated with either acute or chronic liver dysfunction, including, but not limited to:\n\nNon-viral hepatitis (e.g., autoimmune hepatitis, alcoholic hepatitis, drug-induced hepatitis, ischemic hepatitis) Viral hepatitis (e.g., A, B, C, D, E, cytomegalovirus (CMV), Epstein-Barr virus (EBV) rubella (measles)) Reye's syndrome Cirrhosis End Stage Liver Disease\n\nCertain inborn errors of metabolism including, but not limited to:\n\nUrea cycle disorders Organic acidemias Fatty acid oxidation disorders Gastrointestinal bleeding Certain infections (including those caused by urease-producing bacteria)\n\nVarious medications, including, but not limited to:\n\nValproic acid Topiramate Carbamazepine Measurable changes in cognition may be associated with hyperammonemia. With either acute or chronic liver dysfunction, hepatic encephalopathy or hepatic coma may occur with hyperammonemia.\n\nWith an inborn error of metabolism affecting ammonia metabolism, a hyperammonemic crisis may occur with hyperammonemia.\n\nAmmonia levels may increase with increasing dietary protein intake. Ammonia levels can vary throughout the day.\n\nThis Ammonia Device consists of a reusable instrument and a single-use cartridge based system that accepts a single drop of whole blood. It operates on the photometric method. The System measures the color change of a dye in the Cartridge in response to the amount of ammonia in a fixed volume of sample. Ammonia Device system. This is an investigational use only device and the performance characteristics of this product have not been established.\n\n\\[ 1 \\] Adeva, M. M.; Souto, G.; Blanco, N.; Donapetry, C. Ammonium metabolism in humans. Metabolism 2012, 61 (11), 1495-1511. DOI: 10.1016/j.metabol.2012.07.007.\n\n\\[ 2 \\] Bates, R. G.; Pinching, G. D. Acidic Dissociation Constant of Ammonium Ion at 0 to 50°C and the Base Strength of Ammonia. Journal of Research of the National Bureau of Standards 1949, 42, 419-430. DOI: 10.6028/jres.042.037.\n\n\\[ 3 \\] Patel, R.; Kaemingk, B. D.; Carey, W. A.; Block, D. R.; Madigan, T. Proposed Plasma Ammonia Reference Intervals in a Reference Group of Hospitalized Term and Preterm Neonates. The Journal of Applied Laboratory Medicine 2020, 5 (2), 363-369. DOI: 10.1093/jalm/jfz001.\n\n\\[ 4 \\] Berry, S. A.; Lichter-Konecki, U.; Diaz, G. A.; McCandless, S. E.; Rhead, W.; Smith, W.; LeMons, C.; Nagamani, S. C. S.; Coakley, D. F.; Mokhtarani, M.; et al. Glycerol phenylbutyrate treatment in children with urea cycle disorders: Pooled analysis of short and long-term ammonia control and outcomes. Molecular Genetics and Metabolism 2014, 112 (1), 17-24. DOI: 10.1016/j.ymgme.2014.02.007.\n\n\\[ 5 \\] Häberle, J.; Burlina, A.; Chakrapani, A.; Dixon, M.; Karall, D.; Lindner, M.; Mandel, H.; Martinelli, D.; Pintos-Morell, G.; Santer, R.; et al. Suggested guidelines for the diagnosis and management of urea cycle disorders: First revision. Journal of Inherited Metabolic Disease 2019, 42 (6), 1192-1230. DOI: 10.1002/jimd.12100.\n\n\\[ 6 \\] Lee, B.; Diaz, G. A.; Rhead, W.; Lichter-Konecki, U.; Feigenbaum, A.; Berry, S. A.; Le Mons, C.; Bartley, J. A.; Longo, N.; Nagamani, S. C.; et al. Blood ammonia and glutamine as predictors of hyperammonemic crises in patients with urea cycle disorder. Genet Med 2015, 17 (7), 561-568. DOI: 10.1038/gim.2014.148 From NLM.\n\n\\[ 7 \\] Weiner, I. D.; Hamm, L. L. Molecular mechanisms of renal ammonia transport. Annu Rev Physiol 2007, 69, 317-340. DOI: 10.1146/annurev.physiol.69.040705.142215.\n\n\\[ 8 \\] Levitt, D. G.; Levitt, M. D. A model of blood-ammonia homeostasis based on a quantitative analysis of nitrogen metabolism in the multiple organs involved in the production, catabolism, and excretion of ammonia in humans. Clin Exp Gastroenterol 2018, 11, 193-215. DOI: 10.2147/CEG.S160921.\n\n\\[ 9 \\] Mohiuddin, S. S.; Khattar, D. Biochemistry, Ammonia. In StatPearls, 2025. \\[ 10 \\] Balistreri, W.; Rej, R. Liver Function. In Tietz Fundamentals of Clinical Chemistry. 4th ed.Philadelphia, Burtis, C., Ashwood, E. Eds.; WB Saunders, 1996; pp 539-568."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'minimumAge': '12 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Confirmed ammonia disorder such as\n\n * Ornithine transcarbamylase deficiency\n * Systemic primary carnitine deficiency\n * Type I citrullinemia\n * Argininosuccinic aciduria\n * Isolated methylmalonic acidemia\n * Type II citrullinemia\n * Propionic acidemia\n * Isovaleric acidemia\n * Multiple acyl-CoA dehydrogenase deficiency\n * Pyruvate carboxylase deficiency\n * Argininemia (arginase deficiency)\n * Carbamoyl phosphate synthase I deficiency\n * Dihydrolipoamide dehydrogenase deficiency\n * Lysinuric protein intolerance\n * Hyperornithinemia-hyperammonemia-homocitrullinuria\n * Carnitine-acylcarnitine translocase deficiency\n * Carbonic anhydrase VA deficiency\n * N-acetyl glutamate synthetase deficiency\n* English Literacy\n\nExclusion Criteria:\n\n* Incarcerated\n* Presence of a non-inborn error of metabolism medical condition associated with abnormal ammonia metabolism (e.g., end stage liver disease).\n* Unable to read in English'}, 'identificationModule': {'nctId': 'NCT06953505', 'briefTitle': 'At Home Ammonia Monitoring of Inborn Errors of Ammonia Metabolism', 'organization': {'class': 'INDUSTRY', 'fullName': 'Sequitur Health Corp.'}, 'officialTitle': 'Pilot Study of At Home Ammonia Monitoring in Patients With an Inborn Error of Ammonia Metabolism', 'orgStudyIdInfo': {'id': 'HD112243'}, 'secondaryIdInfos': [{'id': '1R44HD112243', 'link': 'https://reporter.nih.gov/quickSearch/1R44HD112243', 'type': 'NIH'}, {'id': 'STUDY00025898', 'type': 'OTHER', 'domain': 'Oregon Health & Science University'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ammonia Device', 'interventionNames': ['Diagnostic Test: Ammonia Study Device']}], 'interventions': [{'name': 'Ammonia Study Device', 'type': 'DIAGNOSTIC_TEST', 'description': 'Ammonia study device for capillary ammonia measurement', 'armGroupLabels': ['Ammonia Device']}]}, 'contactsLocationsModule': {'locations': [{'zip': '97239-3098', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health & Science University', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}], 'overallOfficials': [{'name': 'Marylaura L Thomas, Ph.D.', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Sequitur Health Corp.'}, {'name': 'Leslie F. Thomas, M.D.', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Sequitur Health Corp.'}]}, 'ipdSharingStatementModule': {'infoTypes': ['STUDY_PROTOCOL', 'ICF'], 'timeFrame': 'Upon publication in a peer-reviewed publication and in perpetuity once the publication is available.', 'ipdSharing': 'YES', 'description': 'Deidentified primary outcome participant data sets for results used in publications will be made available for sharing at the time the results are published in a peer-review publication.\n\nDeidentified secondary outcome participant data sets will be made available upon request to Sequitur Health Corp. after a data sharing agreement is signed.', 'accessCriteria': 'All peer reviewed publications will be published open-access so anyone with an internet connection will be able to access the publication, the data contained within the publication, and any supplementary information to the publication.\n\nSecondary outcome individual participant data that may not be included in a publication will be made available after a data sharing agreement is executed between the receiving party and Sequitur Health Corp.. To request secondary outcome data, after the completion of the study, please contact Sequitur Health Corp. at info@sequiturhealth.com or 1-855-445-3889.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Sequitur Health Corp.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)', 'class': 'NIH'}, {'name': 'Oregon Health and Science University', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}