Doxycycline Outcomes in Lupus Erythematosus

Study Overview
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Brief Summary
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Cardiovascular disease, specifically from atherosclerosis, is the major cause of mortality in SLE in developed countries. In a recent study the investigators have shown that high sensitivity C reactive protein (hs-CRP) is higher in SLE patients with (versus without) coronary calcium, a measure of subclinical atherosclerosis. In an ongoing two year intervention trial of atorvastatin, the investigators will determine if statins retard coronary calcium and reduce hs-CRP. However, 10% of the patients in the trial were intolerant of statins. The investigators want to now investigate whether there are additional, and potentially safer ways, to reduce hs-CRP in SLE. In this study, the investigators will determine if doxycycline reduces hs-CRP and other vascular inflammatory markers including interleukin 6 (IL-6), soluble vascular cell adhesion molecule (sVCAM-1), soluble inter cell adhesion molecule (s-ICAM-1) and matrix metalloproteinase 9 (MMP-9) in SLE.

Official Title
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Doxycycline Outcomes in Lupus Erythematosus: (DOLE)

Conditions
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Cardiovascular Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Doxycycline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a clinical diagnosis of SLE, with a hs-CRP above > 3mg/L, (high risk level) for the last 3 months, are eligible. Patients must be 18 years of age or older and able to give informed consent. Contraception other than OCPs is necessary if a woman is at risk for pregnancy. Exclusion Criteria: SLE patients who are allergic to doxycycline or other tetracyclines. Patients who are pregnant or are planning to become pregnant. Patients who are on oral contraceptives (any method of contraception other than OCPs can be used. Tetracycline use within the previous 2 weeks of enrollment. Patients who are currently on statins will be excluded, because statins might reduce hs- CRP. Patients who are on warfarin. Patients whose most recent EKG shows significant cardiac dysrhythmias or heart block.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo | Drug: Placebo<br>* This is a randomized double-blind clinical trial of doxycycline 20 mg bid versus 100mg bid versus placebo, given for 3 months, to be conducted at a single center (JHH).<br>|
| Active Comparator: Doxycycline<br>Doxycycline | Drug: Doxycycline<br>* Doxycycline 20 mg bid versus Doxycycline 100 mg bid versus placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine whether doxycycline 20 mg bid (periostat) versus 100mg bid versus placebo is more effective in reducing hs-CRP. |  | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Inflammatory markers of cardiovascular disease