Systemic Lupus Erythematosus
Conditions
Keywords
SLE, atherosclerosis, omega-3
Brief summary
The investigators hypothesize that low-dose dietary supplementation with omega-3 fish oil will improve disease activity and endothelial function in Systemic Lupus Erythematosus (SLE) patients.
Detailed description
Patients with SLE have a fifty-fold increased risk of myocardial infarction. This risk is not totally explained by traditional cardiovascular risk factors. In a previous double-blind study of atorvastatin in SLE, there was no reduction in surrogate measures of coronary artery disease (coronary calcium, coronary IMT, carotid plaque) and no effect on inflammatory markers such as ICAM, VCAM, IL-6 and CRP. We need to find novel approaches to reduce coronary artery disease in SLE. In a preliminary study, omega-3 was shown to improve flow mediated dilation of the brachial artery, oxidative stress and disease activity in lupus patients. In this study we will determine if omega-3 improves brachial artery flow dilation, disease activity and other vascular inflammatory markers (IL-6, s-VCAM-1, s-ICAM-1) in SLE, in a double-blind placebo-controlled trial.
Interventions
DRUGOmega-3
Omega-3-acid ethyl esters (Lovaza) 3 gram once a day for 12 weeks
DEVICEflow-mediated dilation of the brachial artery
flow-mediated dilation of the brachial artery measurement at baseline and after 12 weeks
OTHERcorn starch
3 capsules qd for 12weeks
Sponsors
Michelle Petri M.D.,MPH
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients with a clinical diagnosis of SLE are eligible. * Patients must be 18 years of age or older and able to give informed consent.
Exclusion criteria
* SLE patients who are allergic to fish oil or any omega 3 product. * Patients who are pregnant or are planning to become pregnant or are nursing. * Omega-3 use within the previous 6 weeks of enrollment. * Use of warfarin or heparin. * Patients who have coronary artery disease.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Effect on Brachial Artery Flow Dilation by Omega-3 Versus Placebo. | 12 weeks | The assessment measured mean brachial artery diameter at pre-treatment(baseline) and post-treatment (after 12 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Omega-3 Versus Placebo on Disease Activity in SLE. | pre-treatment(baseline) and post-treatment (after 12 weeks) | The assessment measured change in disease activities using SELENA-SLEDAI (Systemic Lupus Erythematosus Disease Activity Index Selena Modification - range 0-105) and PGA (Physician Global Assessment - range 0-3) comparing pre-treatment(baseline) vs post-treatment (after 12 weeks). SELENA-SLEDAI - range 0-105, high score indicates high disease activity - weighted sum of sub-scale is used as total score. PGA - range 0-3, high score indicates high disease activity. |
| Effect on Markers of Inflammation: ICAM and VCAM by Omega-3 Versus Placebo. | pre-treatment(baseline) and post-treatment (after 12 weeks) | The inflammatory markers (sICAM-1 and sVCAM-1) were assessed and compared before and after treatment. change from baseline were reported. |
Countries
United States
Participant flow
Recruitment details
106 patients were consented and 87 were randomized. Patients were part of the Hopkins Lupus Cohort seen quarterly.
Pre-assignment details
Some of patients were excluded before being randomized for several reasons including change of mind by patient, became pregnant, diagnosed with breast ca. Therefore a total of 87 patients started the trial.
Participants by arm
| Arm | Count |
|---|---|
| Fish Oil 3 g of Omega-3 (1.8 g eicosapentaenoic acid, 1.2 g docosahexaenoic acid ethyl esters) | 42 |
| Placebo corn starch | 45 |
| Total | 87 |
Baseline characteristics
| Characteristic | Placebo | Fish Oil | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 45 Participants | 42 Participants | 87 Participants |
| Age, Continuous | 45.5 years STANDARD_DEVIATION 10.8 | 48.9 years STANDARD_DEVIATION 10.6 | 47.2 years STANDARD_DEVIATION 10.4 |
| Region of Enrollment United States | 45 participants | 42 participants | 87 participants |
| Sex: Female, Male Female | 39 Participants | 41 Participants | 80 Participants |
| Sex: Female, Male Male | 6 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 42 | 0 / 43 |
| serious Total, serious adverse events | 0 / 42 | 0 / 43 |
Outcome results
Primary
Effect on Brachial Artery Flow Dilation by Omega-3 Versus Placebo.
The assessment measured mean brachial artery diameter at pre-treatment(baseline) and post-treatment (after 12 weeks).
Time frame: 12 weeks
Population: Patients who successfully completed the trial.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega-3 | Effect on Brachial Artery Flow Dilation by Omega-3 Versus Placebo. | Post-treatment baseline diameter | 0.32 cm | Standard Deviation 0.04 |
| Omega-3 | Effect on Brachial Artery Flow Dilation by Omega-3 Versus Placebo. | Pre-treatment baseline diameter | 0.32 cm | Standard Deviation 0.06 |
| Placebo | Effect on Brachial Artery Flow Dilation by Omega-3 Versus Placebo. | Post-treatment baseline diameter | 0.33 cm | Standard Deviation 0.06 |
| Placebo | Effect on Brachial Artery Flow Dilation by Omega-3 Versus Placebo. | Pre-treatment baseline diameter | 0.33 cm | Standard Deviation 0.06 |
Comparison: Statistical analysis system (SAS) software was used (SAS Institute Inc. Cary, North Carolina, SAS 9.2). Baseline demographic and clinical characteristics were summarized using appropriate descriptive statistics and compared across treatment groups using Chi-square. Two-sample t tests were used in the statistical analysis of the FMD outcomes. ANCOVA was used to compare the groups with respect to changes in clinical variables adjusting for baseline values.p-value: 0.87t-test, 2 sided
Secondary
Effect of Omega-3 Versus Placebo on Disease Activity in SLE.
The assessment measured change in disease activities using SELENA-SLEDAI (Systemic Lupus Erythematosus Disease Activity Index Selena Modification - range 0-105) and PGA (Physician Global Assessment - range 0-3) comparing pre-treatment(baseline) vs post-treatment (after 12 weeks). SELENA-SLEDAI - range 0-105, high score indicates high disease activity - weighted sum of sub-scale is used as total score. PGA - range 0-3, high score indicates high disease activity.
Time frame: pre-treatment(baseline) and post-treatment (after 12 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega-3 | Effect of Omega-3 Versus Placebo on Disease Activity in SLE. | SELENA-SLEDAI | 1.5 Units on a scale | Standard Deviation 2 |
| Omega-3 | Effect of Omega-3 Versus Placebo on Disease Activity in SLE. | PGA | 0.49 Units on a scale | Standard Deviation 0.52 |
| Placebo | Effect of Omega-3 Versus Placebo on Disease Activity in SLE. | SELENA-SLEDAI | 1.5 Units on a scale | Standard Deviation 2.5 |
| Placebo | Effect of Omega-3 Versus Placebo on Disease Activity in SLE. | PGA | 0.41 Units on a scale | Standard Deviation 0.49 |
p-value: 0.1801t-test, 2 sided
Secondary
Effect on Markers of Inflammation: ICAM and VCAM by Omega-3 Versus Placebo.
The inflammatory markers (sICAM-1 and sVCAM-1) were assessed and compared before and after treatment. change from baseline were reported.
Time frame: pre-treatment(baseline) and post-treatment (after 12 weeks)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Omega-3 | Effect on Markers of Inflammation: ICAM and VCAM by Omega-3 Versus Placebo. | sICAM-1 | -1.61 ng/ml | Standard Deviation 40.27 |
| Omega-3 | Effect on Markers of Inflammation: ICAM and VCAM by Omega-3 Versus Placebo. | sVCAM-1 | -17.52 ng/ml | Standard Deviation 101.65 |
| Placebo | Effect on Markers of Inflammation: ICAM and VCAM by Omega-3 Versus Placebo. | sVCAM-1 | 26.57 ng/ml | Standard Deviation 135.98 |
| Placebo | Effect on Markers of Inflammation: ICAM and VCAM by Omega-3 Versus Placebo. | sICAM-1 | -5.56 ng/ml | Standard Deviation 48.74 |