The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients

Study Overview
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Brief Summary
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Systemic lupus erythematosus (SLE) is a chronic multi-system autoimmune disease impacting the physical, social, psychological health and quality of life of patients. Fatigue and pain are aspects of SLE patients which affect their health related quality of life (HRQOL). The purpose of this study is to determine the effect of milnacipran on fatigue in SLE patients with widespread pain (WSP) or fibromyalgia syndrome (FMS). A secondary objective will be to determine the effect of milnacipran on pain and quality of life measurements. Fifty SLE male and female patients, 18 years and older, will be recruited for a 15-week study, in which patients will be receive 14 weeks of milnacipran 50-100 mg twice a day or placebo. Measurements of fatigue, pain, and HRQOL will be compared between the milnacipran and placebo groups at the screening visit, baseline visit, week number 6, and week number 14. Milnacipran has been shown to be an effective treatment for pain, fatigue and physical function in FMS patients. To date, no clinical trials have demonstrated efficacy for the treatment of fatigue in SLE patients with concomitant WSP or FMS. The investigators hypothesize, based on FMS studies, that the milnacipran treated patients will have less fatigue than those in the placebo group. In addition, compared to control arm, those treated with the study drug will have less pain and improved quality of life.

Official Title
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The Effect of Milnacipran on Fatigue and Quality of Life in a Lupus Cohort

Conditions
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Systemic Lupus Erythematosus, Widespread Pain, Fibromyalgia

Intervention / Treatment
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* Drug: Milnacipran


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female or male age 18 or older. Has fulfilled the 1997 classification criteria for SLE. Has chronic WSP or FMS. Score a 40 or more on the visual analog score (VAS) for fatigue. Exclusion Criteria: Has a chronic inflammatory autoimmune condition other than SLE. Has an acute or uncontrolled co-morbid medical condition. Uncontrolled narrow angle glaucoma. Has been hospitalized in the last four months for a lupus flare. Pregnant or breast feeding. Has a current or prior major depressive disorder or other DSM IV diagnosis within 2 years of the screening visit. The use of antidepressants, MAO inhibitors, antipsychotics or lithium The use of pregabalin or milnacipran within 2-4 weeks. Has received cyclophosphamide and or rituximab within 4 and 6 months. Unable to speak, read, and understand English.

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Milnacipran<br>Patients administered milnacipran will receive a dose escalation to 50 mg twice a day over 12 days and continued at this dose until week 6. If tolerated and a 15% improvement in fatigue from baseline is achieved by assessment on the FSS, then patients will continue taking 50 mg twice a day until the end of the study on day 98 (week 14). Otherwise, the dose of milnacipran will be titrated upward to 100 mg twice a day over 12 days and continued at this dose until day 98 (week 14). | Drug: Milnacipran<br>* After dose escalations, patients will receive Milnacipran administered at 50 mg twice a day after for 12 weeks or milnacipran 50 mg twice day for 4 weeks and then 100 mg twice a day for an additional 6 weeks depending on tolerability and fatigue response.<br>* Other names: Savella;|
| Placebo Comparator: Placebo<br>Placebo tablets administered orally twice a day for 14 weeks. | Drug: Milnacipran<br>* After dose escalations, patients will receive Milnacipran administered at 50 mg twice a day after for 12 weeks or milnacipran 50 mg twice day for 4 weeks and then 100 mg twice a day for an additional 6 weeks depending on tolerability and fatigue response.<br>* Other names: Savella;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | A change in fatigue from baseline will be assessed with values obtained at week 14 using the Fatigue Severity Scale (FSS) in both the treatment and control groups. | Baseline and Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fatigue | A change in fatigue will be assessed with values obtained at baseline and week 6 using the FSS and Visual Analogue Score (VAS) Fatigue. | Baseline and Week 6 | 
| Pain | A change in pain will be assessed with values obtained at baseline, week 6, and 14 using the VAS Pain, and the Short Form - McGill Pain Questionnaire (SF-MPQ). | Baseline, week 6 and week 14 | 
| Health related quality of life | Health related quality of life will be assessed with values obtained at baseline, week 6, and 14 using the Short form-36 (SF-36). | Baseline, week 6 and week 14 | 
| Overall health status | A change in overall health status will be assessed using the Patient Global Impression of Change (PGIC) at baseline, week 6, and 14. | Baseline, week 6 and week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Widespread Pain, Fibromyalgia, Fatigue, Pain, Quality of Life