Crohn DiseasePhase 4NCT02349594
Immune Modulation by Parenteral Fish Oil in Patients With Crohn's Disease
A Phase 4 study testing Omegaven 10% and Intralipid 20% in people with Crohn Disease, run by Radboud University Medical Center at 1 site in Netherlands.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- Omegaven 10% and Intralipid 20%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2014to Sep 2015
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- Patients with other active inflammatory / immune mediated underlying diseases
- Smoking > 5 cigarettes a day
- Diet with >2 portions of fatty fish (tuna, salmon, mackerel, herring, and trout) a week
- History of metabolic disorder (especially diabetes or lipid disorders)
- Crohn's disease activity, including the presence of active fistulas
- On need for medical (other than 5-aminosalicylic acid preparations) or surgical treatment for Crohn's disease activity
Show all 14Show fewer
- Use of non-steroidal anti-inflammatory drugs or aspirin
- C-reactive protein levels of >10 mg/l
- History of venous or arterial thrombosis
- Active malignancy
- Presence of severe pulmonary, cardiovascular, renal, liver, coagulation or hematological disease
- Pregnancy or lactation
- Age <18 yrs
- Allergy for one of the following components: fish, chicken, eggs or soy beans
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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
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.
Read the detailed description
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.
Study design: Single center, randomized, single blinded, lipid-controlled, cross-over pilot trial.
Study 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.
Intervention: 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.
Main 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.
- Conditions
- Crohn Disease
- Being tested
- Omegaven 10%, Intralipid 20%
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Omegaven 10%Drug
Also called fish oil, N-3 polyunsaturated fatty acids atty acids
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.
Intralipid 20%Drug
Also called soybean oil, N-6 polyunsaturated fatty acids atty acids
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.
| Study group | Role | What they receive |
|---|---|---|
| treatment order A | Active comparator | Participants in this arm first receive 'Omegaven 10%' and after crossing over the 'Intralipid 20%' Receives: Drug: Omegaven 10%; Drug: Intralipid 20% |
| treament order B | Active comparator | Participants in this arm first receive 'Intralipid 20%' and after crossing over the 'Omegaven 10%' Receives: Drug: Omegaven 10%; Drug: Intralipid 20% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of TNF-α production in pg/ml
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.
Measured: day 0 and day 4
Secondary outcomes (10)
short term change in leukocyte functions
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
Measured: day 0 and day 4
long term change in leukocyte functions
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.
Measured: day 0 and day 11
change in Oxygen radical production by neutrophils
Differences are compared by paired t-test or wilcoxon signed rank test
Measured: day 0 and day 4
change in Oxygen radical production by neutrophils
Differences are compared by paired t-test or wilcoxon signed rank test.
Measured: day 0 and day 11
short term effects on in cytokine production
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.
Measured: day 0 and day 4
Long term effects on in cytokine production
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.
Measured: day 0 and day 11
Composition of phospholipids in the cell membrane
to evaluate fatty acid incorporationDifferences are compared by paired t-test or wilcoxon signed rank test.
Measured: day 0, day4 and day 11
Change of TNF-α production in pg/ml
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.
Measured: day 0 and day 11
(anti-) Oxidant status and oxidative damage
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.
Measured: day 0 and day 4
(anti-) Oxidant status and oxidative damage
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.
Measured: day 0 and day 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jan 2015 (estimated)
- Study startJan 2014
- Primary completionMay 2015
- Study completionSep 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 6 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- G. Wanten, MD, PhD, Study director, Radboud University Nijmegen Medical CenterF. Hoentjen, MD, PhD, Principal investigator, Radboud University Nijmegen Medical CenterD de Jong, MD, PhD, Principal investigator, Radboud University Nijmegen Medical CenterP. Calder, MD, PhD, Principal investigator, University Hospital Southampton NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02349594
- Sponsor's protocol ID
- GW/MB/42964
- Other IDs
- 2013-001212-30
- Status last verified
- Nov 2015
- First submitted
- 16 Jan 2015
- Last updated
- 10 Nov 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT02349594
- Acronym / sponsor ID
- GW/MB/42964
- Conditions
- Crohn Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- Jan 2014
- Primary completion
- May 2015 (actual)
- Study completion
- Sep 2015 (actual)
- First posted
- 29 Jan 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design: Single center, randomized, single blinded, lipid-controlled, cross-over pilot trial.
Study 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.
Intervention: 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.
Main 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| treatment order A | Active comparator | Drug: Omegaven 10%, Drug: Intralipid 20%Participants in this arm first receive 'Omegaven 10%' and after crossing over the 'Intralipid 20%' |
| treament order B | Active comparator | Drug: Omegaven 10%, Drug: Intralipid 20%Participants in this arm first receive 'Intralipid 20%' and after crossing over the 'Omegaven 10%' |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (14 listed)
- Patients with other active inflammatory / immune mediated underlying diseases
- Smoking > 5 cigarettes a day
- Diet with >2 portions of fatty fish (tuna, salmon, mackerel, herring, and trout) a week
- History of metabolic disorder (especially diabetes or lipid disorders)
- Crohn's disease activity, including the presence of active fistulas
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Omegaven 10%Also: fish oil, N-3 polyunsaturated fatty acids atty acidsintravenous 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. | Drug | treament order B, treatment order A |
| Intralipid 20%Also: soybean oil, N-6 polyunsaturated fatty acids atty acidsintravenous 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. | Drug | treament order B, treatment order A |
Primary outcome
Change of TNF-α production in pg/ml
Time frame: day 0 and day 4
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.
10 secondary outcomes
short term change in leukocyte functions
Time frame: day 0 and day 4
long term change in leukocyte functions
Time frame: day 0 and day 11
change in Oxygen radical production by neutrophils
Time frame: day 0 and day 4
change in Oxygen radical production by neutrophils
Time frame: day 0 and day 11
short term effects on in cytokine production
Time frame: day 0 and day 4
Long term effects on in cytokine production
Time frame: day 0 and day 11
Composition of phospholipids in the cell membrane
Time frame: day 0, day4 and day 11
Change of TNF-α production in pg/ml
Time frame: day 0 and day 11
(anti-) Oxidant status and oxidative damage
Time frame: day 0 and day 4
(anti-) Oxidant status and oxidative damage
Time frame: day 0 and day 11
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
G. Wanten, MD, PhD study director
Radboud University Nijmegen Medical Center
F. Hoentjen, MD, PhD principal investigator
Radboud University Nijmegen Medical Center
D de Jong, MD, PhD principal investigator
Radboud University Nijmegen Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Omegaven 10% and Intralipid 20% in people with Crohn Disease, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Nov 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change of TNF-α production in pg/ml (time frame: day 0 and day 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2015.