Ignite Creation Date:
2025-12-25 @ 1:39 AM
Ignite Modification Date:
2026-03-10 @ 11:33 PM
Study NCT ID:
NCT02349594
Status:
COMPLETED
Last Update Posted:
2015-11-10
First Post:
2015-01-16
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Immune Modulation by Parenteral Fish Oil in Patients With Crohn's Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003424', 'term': 'Crohn Disease'}], 'ancestors': [{'id': 'D015212', 'term': 'Inflammatory Bowel Diseases'}, {'id': 'D005759', 'term': 'Gastroenteritis'}, {'id': 'D005767', 'term': 'Gastrointestinal Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D007410', 'term': 'Intestinal Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005395', 'term': 'Fish Oils'}, {'id': 'D013024', 'term': 'Soybean Oil'}], 'ancestors': [{'id': 'D009821', 'term': 'Oils'}, {'id': 'D008055', 'term': 'Lipids'}, {'id': 'D004042', 'term': 'Dietary Fats, Unsaturated'}, {'id': 'D004041', 'term': 'Dietary Fats'}, {'id': 'D005223', 'term': 'Fats'}, {'id': 'D005224', 'term': 'Fats, Unsaturated'}, {'id': 'D010938', 'term': 'Plant Oils'}, {'id': 'D028321', 'term': 'Plant Preparations'}, {'id': 'D001688', 'term': 'Biological Products'}, {'id': 'D045424', 'term': 'Complex Mixtures'}, {'id': 'D005502', 'term': 'Food'}, {'id': 'D000066888', 'term': 'Diet, Food, and Nutrition'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}, {'id': 'D019602', 'term': 'Food and Beverages'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE4'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'SINGLE', 'whoMasked': ['OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 6}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-01'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-11', 'completionDateStruct': {'date': '2015-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-11-09', 'studyFirstSubmitDate': '2015-01-16', 'studyFirstSubmitQcDate': '2015-01-23', 'lastUpdatePostDateStruct': {'date': '2015-11-10', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2015-01-29', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-05', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change of TNF-α production in pg/ml', 'timeFrame': 'day 0 and day 4', 'description': 'whole blood cultures are stimulated with 1 ng/ml lipopolysaccharide for 4 hours. TNF-alpha levels are measured in the supernatant with an enzyme-linked immunosorbent assay. Differences are compared by paired t-test or wilcoxon signed rank test.'}], 'secondaryOutcomes': [{'measure': 'short term change in leukocyte functions', 'timeFrame': 'day 0 and day 4', 'description': 'Change in expression of cell surface markers on neutrophils and monocytes (CD11, CD66, CD62 and CD63) by immune fluorescent staining and subsequent flowcytometric analysis. Between day 0 and day 4 patients receive on intralipid or omegaven 3 consecutive days. Differences are compared by paired t-test or wilcoxon signed rank test'}, {'measure': 'long term change in leukocyte functions', 'timeFrame': 'day 0 and day 11', 'description': 'Change in expression of cell surface markers on neutrophils and monocytes (CD11, CD66, CD62 and CD63) by immune fluorescent staining and subsequent flowcytometric analysis. Differences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': 'change in Oxygen radical production by neutrophils', 'timeFrame': 'day 0 and day 4', 'description': 'Differences are compared by paired t-test or wilcoxon signed rank test'}, {'measure': 'change in Oxygen radical production by neutrophils', 'timeFrame': 'day 0 and day 11', 'description': 'Differences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': 'short term effects on in cytokine production', 'timeFrame': 'day 0 and day 4', 'description': 'whole blood cultures are stimulated with 1 ng/ml lipopolysaccharide for 24 hours. Interleukin (IL)-1B, Il-6 and IL-10 levels are measured in the supernatant with an enzyme-linked immunosorbent assay. Differences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': 'Long term effects on in cytokine production', 'timeFrame': 'day 0 and day 11', 'description': 'whole blood cultures are stimulated with 1 ng/ml lipopolysaccharide for 24 hours. Il-1B, Il-6 and IL-10 levels (pg/ml ) are measured in the supernatant with an enzyme-linked immunosorbent assay . Differences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': 'Composition of phospholipids in the cell membrane', 'timeFrame': 'day 0, day4 and day 11', 'description': 'to evaluate fatty acid incorporationDifferences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': 'Change of TNF-α production in pg/ml', 'timeFrame': 'day 0 and day 11', 'description': 'whole blood cultures are stimulated with 1 ng/ml lipopolysaccharide for 4 hours. TNF-alpha levels are measured in the supernatant with an enzyme-linked immunosorbent assay. Differences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': '(anti-) Oxidant status and oxidative damage', 'timeFrame': 'day 0 and day 4', 'description': 'Oxidative stress will be measured by both lipid and protein peroxidation and antioxidant capacity. Differences are compared by paired t-test or wilcoxon signed rank test.'}, {'measure': '(anti-) Oxidant status and oxidative damage', 'timeFrame': 'day 0 and day 11', 'description': 'Oxidative stress will be measured by both lipid and protein peroxidation and antioxidant capacity. Differences are compared by paired t-test or wilcoxon signed rank test.'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Crohn Disease']}, 'descriptionModule': {'briefSummary': 'To evaluate the effects of infusion of a Fish oil-based lipid emulsion on TNF-α production and other relevant immune functions. A soybean oil emulsion, rich in the omega-6 polyunsaturated fatty acid linoleic acid, will serve as control.', 'detailedDescription': "Rationale: Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, exerts a range of anti-inflammatory actions that render it a potential therapeutic agent to treat Crohn's disease, a chronic inflammatory disease that primarily affects the bowel. Recent evidence suggests that a lack of effect in previous studies might be due to the fact that genetic background was not taken into account. For instance, a study in healthy subjects showed that production of the pro-inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α) following FO supplementation decreased in individuals within the highest tertile of pre-supplementational TNF-α production, remained unaltered in the middle tertile, and increased in the lowest tertile of pre-supplementational TNF-α production. TNF-α plays a pivotal role in the pathogenesis of Crohn's disease, hence the treatment with anti-TNF-α agents. Based on these notions, and because FO supplementation via the enteral route is strongly dose limited due to fat-induced side effects such as diarrhea, we hypothesize that parenteral FO supplementation might be beneficial in those patients with Crohn's disease with a high inherent TNF-α production.\n\nStudy design: Single center, randomized, single blinded, lipid-controlled, cross-over pilot trial.\n\nStudy population: Adult patients with Crohn's disease with previous bowel surgery, currently in remission (without the need for immunosuppressive drugs) and with a high inherent TNF-α production.\n\nIntervention: First, patients with a high inherent TNF-α will be identified by assessment of TNF-α production in a group 100 patients who meet in- and exclusion criteria. Patients within the highest tertile will be classified as high producers. Next, 5 patients within the highest tertile will be randomized to receive intravenous administration of 20% (w/v) lipid-control (Intralipid®), and, after crossing over, 10% (w/v) fish oil emulsion (Omegaven®), or vice-versa for 1 hour on three consecutive days at a dose of 0.2 g/kg bodyweight /hr. Study parameters will be assessed in blood drawn prior to the first infusion (T=0) and 1 (T=4) and 8 days (T=11) after the third infusion. Between the two treatment arms, there will be a wash-out interval of at least 2-3 weeks.\n\nMain study parameters/endpoints: Early (T=day 4) and late (T=day 11) effects of infusions on TNF-α production by whole blood cultures. Secondary outcomes: effect on leukocyte counts, leukocyte functions and on (anti-)oxidant status, the occurrence of oxidative damage and analysis of specific Single Nucleotide Polymorphisms (SNPs) related to TNF-α production."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Adult patients with Crohn's disease with previous bowel surgery, currently in remission (without the need for immunosuppressive drugs) and with a high inherent TNF-α production.\n\nExclusion Criteria:\n\n* Patients with other active inflammatory / immune mediated underlying diseases\n* Smoking \\> 5 cigarettes a day\n* Diet with \\>2 portions of fatty fish (tuna, salmon, mackerel, herring, and trout) a week\n* History of metabolic disorder (especially diabetes or lipid disorders)\n* Crohn's disease activity, including the presence of active fistulas\n* On need for medical (other than 5-aminosalicylic acid preparations) or surgical treatment for Crohn's disease activity\n* Use of non-steroidal anti-inflammatory drugs or aspirin\n* C-reactive protein levels of \\>10 mg/l\n* History of venous or arterial thrombosis\n* Active malignancy\n* Presence of severe pulmonary, cardiovascular, renal, liver, coagulation or hematological disease\n* Pregnancy or lactation\n* Age \\<18 yrs\n* Allergy for one of the following components: fish, chicken, eggs or soy beans"}, 'identificationModule': {'nctId': 'NCT02349594', 'briefTitle': "Immune Modulation by Parenteral Fish Oil in Patients With Crohn's Disease", 'organization': {'class': 'OTHER', 'fullName': 'Radboud University Medical Center'}, 'officialTitle': "Modulation of Immune Function by Parenteral Fish Oil in Patients With Crohn's Disease and High Inherent Tumor Necrosis Factor-alpha Production: a Randomized, Single Blinded, Cross-over Study", 'orgStudyIdInfo': {'id': 'GW/MB/42964'}, 'secondaryIdInfos': [{'id': '2013-001212-30', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'treatment order A', 'description': "Participants in this arm first receive 'Omegaven 10%' and after crossing over the 'Intralipid 20%'", 'interventionNames': ['Drug: Omegaven 10%', 'Drug: Intralipid 20%']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'treament order B', 'description': "Participants in this arm first receive 'Intralipid 20%' and after crossing over the 'Omegaven 10%'", 'interventionNames': ['Drug: Omegaven 10%', 'Drug: Intralipid 20%']}], 'interventions': [{'name': 'Omegaven 10%', 'type': 'DRUG', 'otherNames': ['fish oil', 'N-3 polyunsaturated fatty acids atty acids'], 'description': 'intravenous administration 10% (w/v) fish oil emulsion (Omegaven) for 1 hour on three consecutive days at a dose of 0.2 g/kg bodyweight/hr.', 'armGroupLabels': ['treament order B', 'treatment order A']}, {'name': 'Intralipid 20%', 'type': 'DRUG', 'otherNames': ['soybean oil', 'N-6 polyunsaturated fatty acids atty acids'], 'description': 'intravenous administration of 20% (w/v) lipid-control (Intralipid®), for 1 hour on three consecutive days at a dose of 0.2 g/kg bodyweight/hr.', 'armGroupLabels': ['treament order B', 'treatment order A']}]}, 'contactsLocationsModule': {'locations': [{'zip': '6525 GA', 'city': 'Nijmegen', 'country': 'Netherlands', 'facility': 'Radboud University Medical Center', 'geoPoint': {'lat': 51.8425, 'lon': 5.85278}}], 'overallOfficials': [{'name': 'G. Wanten, MD, PhD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Radboud University Nijmegen Medical Center'}, {'name': 'F. Hoentjen, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud University Nijmegen Medical Center'}, {'name': 'D de Jong, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Radboud University Nijmegen Medical Center'}, {'name': 'P. Calder, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University Hospital Southampton NHS Foundation Trust'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Radboud University Medical Center', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}