Ignite Creation Date:
2025-12-25 @ 2:32 AM
Ignite Modification Date:
2026-01-01 @ 12:34 AM
Study NCT ID:
NCT04378634
Status:
COMPLETED
Last Update Posted:
2023-11-07
First Post:
2020-04-27
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Epigenetics of Post-exertional Malaise in Patients With ME/CFS
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D015673', 'term': 'Fatigue Syndrome, Chronic'}, {'id': 'D009043', 'term': 'Motor Activity'}], 'ancestors': [{'id': 'D009135', 'term': 'Muscular Diseases'}, {'id': 'D009140', 'term': 'Musculoskeletal Diseases'}, {'id': 'D004679', 'term': 'Encephalomyelitis'}, {'id': 'D000090862', 'term': 'Neuroinflammatory Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D009468', 'term': 'Neuromuscular Diseases'}, {'id': 'D002908', 'term': 'Chronic Disease'}, {'id': 'D020969', 'term': 'Disease Attributes'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}, {'id': 'D001519', 'term': 'Behavior'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D015444', 'term': 'Exercise'}], 'ancestors': [{'id': 'D009043', 'term': 'Motor Activity'}, {'id': 'D009068', 'term': 'Movement'}, {'id': 'D009142', 'term': 'Musculoskeletal Physiological Phenomena'}, {'id': 'D055687', 'term': 'Musculoskeletal and Neural Physiological Phenomena'}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Randomised Controlled Trial'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 105}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2021-04-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2023-11', 'completionDateStruct': {'date': '2023-04-30', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2023-11-04', 'studyFirstSubmitDate': '2020-04-27', 'studyFirstSubmitQcDate': '2020-05-05', 'lastUpdatePostDateStruct': {'date': '2023-11-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2020-05-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2023-04-30', 'type': 'ACTUAL'}}, 'outcomesModule': {'otherOutcomes': [{'measure': 'General Health', 'timeFrame': 'Baseline', 'description': 'General health will be measured using the Short Form-36 Health Survey (SF-36) questionnaire. The questionnaire returns a score from 0 to 100 where higher scores mean less disability.'}, {'measure': "Gene's polymorphisms", 'timeFrame': 'Baseline', 'description': "Genes' polymorphisms might mediate epigenetic changes. They will be assessed using pyrosequencing technology."}], 'primaryOutcomes': [{'measure': 'DNA methylation', 'timeFrame': 'Baseline through 1 week post intervention', 'description': "DNA methylation measured at several CpGs of the genes' promoter regions using pyrosequencing technology"}], 'secondaryOutcomes': [{'measure': 'Clinical Symptoms', 'timeFrame': 'Baseline through 1 week post intervention', 'description': 'Symptoms reported by the patients using the DePaul Symptoms Questionniare'}, {'measure': 'Pain sensitivity', 'timeFrame': 'Baseline through 1 week post intervention', 'description': 'Sensitivity to mechanical stimuli using a digital algometer (FPXTM, Fisher, Wagner Instruments, Greenwich) as well as heat and cold stimuli using the TSA-II device (Medoc, CA, USA). The devices will be placed, in random order to prevent test order effects, at three different body sites: the skin web between thumb and index finger, trapezius muscle, and proximal third of tibialis anterior muscle, in order to test pain thresholds on non-specific locations both on the extremities and the trunk.'}, {'measure': 'Serum BDNF', 'timeFrame': 'Baseline through 1 week post intervention', 'description': 'BDNF protein expression in serum using Enzyme-Linked Immunosorbent Assay (ELISA) kit for human BDNF'}, {'measure': 'Cortisol response', 'timeFrame': 'Baseline through 1 week post intervention', 'description': 'Cortisol will be measured in saliva and used as a measure of stress responses using LC/MS-MS method.'}]}, 'oversightModule': {'oversightHasDmc': False, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['Chronic Fatigue Syndrome', 'Exercise', 'Epigenetics', 'DNA methylation'], 'conditions': ['Fatigue Syndrome, Chronic']}, 'referencesModule': {'references': [{'pmid': '25111603', 'type': 'BACKGROUND', 'citation': 'de Vega WC, Vernon SD, McGowan PO. DNA methylation modifications associated with chronic fatigue syndrome. PLoS One. 2014 Aug 11;9(8):e104757. doi: 10.1371/journal.pone.0104757. eCollection 2014.'}, {'pmid': '29275786', 'type': 'BACKGROUND', 'citation': 'Vangeel EB, Kempke S, Bakusic J, Godderis L, Luyten P, Van Heddegem L, Compernolle V, Persoons P, Lambrechts D, Izzi B, Freson K, Claes S. Glucocorticoid receptor DNA methylation and childhood trauma in chronic fatigue syndrome patients. J Psychosom Res. 2018 Jan;104:55-60. doi: 10.1016/j.jpsychores.2017.11.011. Epub 2017 Nov 20.'}, {'pmid': '30036399', 'type': 'BACKGROUND', 'citation': 'Trivedi MS, Oltra E, Sarria L, Rose N, Beljanski V, Fletcher MA, Klimas NG, Nathanson L. Identification of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome-associated DNA methylation patterns. PLoS One. 2018 Jul 23;13(7):e0201066. doi: 10.1371/journal.pone.0201066. eCollection 2018.'}]}, 'descriptionModule': {'briefSummary': 'Exploring epigenetic mechanisms of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is crucial to understand the mechanisms underlying its pathophysiology. Three potential candidates have been selected (BDNF, COMT, and HDAC genes). DNA methylation in the promoter regions of those genes will be explored.\n\nThe investigators designed a randomised controlled trial and will enrol 70 patients with ME/CFS and 35 age-, sex-, and BMI-matched healthy controls. Both groups will be randomised in 2 groups and receive either one session of aerobic exercise or a validated test designed to trigger mental stress and mental fatigue. The primary aim is to assess genetic and epigenetic mechanisms of BDNF, COMT and HDAC genes in response to exercise and the stress task.', 'detailedDescription': "The only way to improve the diagnosis and treatment of Myalgic Encephalomyelitis / Chronic Fatigue Syndrome (ME/CFS) is to better understand the mechanisms underlying its pathophysiology. Central nervous system dysfunctions play a major role in ME/CFS and help explaining patients' symptoms, such as general malaise occurring after physical activity (i.e. post-exertional malaise). Therefore, post-exertional malaise in relation to three major candidates involved in central nervous system functioning - brain-derived neurotrophic factor (BDNF), catechol-O-methyltransferase (COMT) and histone de-acetylases (HDAC) - will be explored.\n\nBDNF is a protein involved in crucial functions such as nerve growth, memory and learning, and plays a role in neuronal sensitisation and pain. However, no study has explored the role of BDNF in ME/CFS. Our research group performed a preliminary study which focussed on BDNF in ME/CFS. In a previous study, the investigators assessed DNA methylation (an epigenetic mechanism that contribute to gene expression silencing), and protein expression in serum of the BDNF in patients with ME/CFS and healthy controls. Patients showed significantly less DNA methylation and significantly more BDNF protein. Given these exciting findings, further study is warranted.\n\nCOMT is an enzyme encoded by its homonymous gene. The enzyme degrades catecholamines like dopamine, epinephrine and norepinephrine. Catecholamines have been repeatedly associated with pain, stress, and depression. Lower COMT activity increases catecholamines level, causes hyperalgesia, and has been associated with depressive symptoms.\n\nSimilarly, research on histone acetylation shows that another group of enzymes (Histone de-acetylases, HDACs) are increased during neural sensitisation and pain. However, no research has been done on HDACs in patients with ME/CFS. Interestingly, aerobic exercise has been shown to increase BDNF release and decrease COMT and HDACs activity. Given the detrimental acute effects that exercise can have on patients with ME/CFS, investigators hypothesised that understanding the role of BDNF, COMT, and HDACs following exercise would help elucidating both mechanisms of post-exertional malaise and ME/CFS pathophysiology.\n\nA randomised controlled trial has been designed including 70 patients with ME/CFS and 35 age-, sex-, and BMI-matched healthy controls. Both groups will be randomised in 2 groups. One group will undergo one session of aerobic exercise, and the other group undergoes a validated test designed to trigger mental stress and mental fatigue. All participants will undergo clinical assessments, measurements of pain thresholds, and blood withdrawal before and after the exercise/mental stress exposure. The aims are to assess genetic and epigenetic mechanisms of BDNF, COMT and HDAC genes, as well as the expression of these factors in blood and serum in patients with ME/CFS."}, 'eligibilityModule': {'sex': 'FEMALE', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': True, 'eligibilityCriteria': "Inclusion Criteria:\n\n* diagnosis of ME/CFS established by a MD experienced in the field of internal medicine and ME/CFS - according to the published international criteria developed by the Canadian Consensus Criteria (CCC);\n* age between 18 and 70 years old;\n* body mass index (BMI) below 30 (no obesity).\n\nExclusion Criteria:\n\n* presence of other neurological disorders (Parkinson's disease, Multiple Sclerosis, etc);\n* presence of systemic disorders (lupus erythematosus, rheumatoid arthritis, etc.);\n* presence or history of cardiac disorders (coronary heart disease, history of heart failure, etc);\n* presence or history of cancer;\n* presence or history of neuropathic pain (e.g. pain related to herpes zoster virus);\n* pregnancy;"}, 'identificationModule': {'nctId': 'NCT04378634', 'acronym': 'EPIME', 'briefTitle': 'Epigenetics of Post-exertional Malaise in Patients With ME/CFS', 'organization': {'class': 'OTHER', 'fullName': 'Vrije Universiteit Brussel'}, 'officialTitle': 'The Influence of Epigenetic Modifications and Post-Exertional Malaise in People With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome', 'orgStudyIdInfo': {'id': 'EPIME'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'ME/CFS Exercise', 'description': 'Patients undergoing the physical stress test (aerobic power index)', 'interventionNames': ['Behavioral: Exercise', 'Other: Mental Stress Test']}, {'type': 'EXPERIMENTAL', 'label': 'Patients Stress', 'description': 'Patients undergoing the mental stress task (MIST)', 'interventionNames': ['Behavioral: Exercise', 'Other: Mental Stress Test']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Healthy Exercise', 'description': 'Healthy controls undergoing the physical stress test (aerobic power index)', 'interventionNames': ['Behavioral: Exercise', 'Other: Mental Stress Test']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Healthy Stress', 'description': 'Healthy controls undergoing the mental stress task (MIST)', 'interventionNames': ['Behavioral: Exercise', 'Other: Mental Stress Test']}], 'interventions': [{'name': 'Exercise', 'type': 'BEHAVIORAL', 'otherNames': ['Aerobic Power Index'], 'description': 'Sub-maximal exercise test', 'armGroupLabels': ['Healthy Exercise', 'Healthy Stress', 'ME/CFS Exercise', 'Patients Stress']}, {'name': 'Mental Stress Test', 'type': 'OTHER', 'otherNames': ['Montreal Imaging Stress Task'], 'description': 'Computerised mental arithmetic challenges and social evaluative threat tasks', 'armGroupLabels': ['Healthy Exercise', 'Healthy Stress', 'ME/CFS Exercise', 'Patients Stress']}]}, 'contactsLocationsModule': {'locations': [{'zip': '1090', 'city': 'Brussels', 'country': 'Belgium', 'facility': 'UZ Brussel', 'geoPoint': {'lat': 50.85045, 'lon': 4.34878}}], 'overallOfficials': [{'name': 'Jo Nijs, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Vrije Universiteit Brussel'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Vrije Universiteit Brussel', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'PhD, principal investigator', 'investigatorFullName': 'Andrea Polli', 'investigatorAffiliation': 'Vrije Universiteit Brussel'}}}}