Circadian RA Study in Rheumatoid Arthritis Subjects

Study Overview
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Brief Summary
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Primary objective: To determine the changes in circadian activity rhythms and disease activity in rheumatoid arthritis (RA) patients from pre-treatment to one month after Enbrel initiation. Secondary objectives: To determine if there is an association between changes in circadian rhythm and changes in disease activity in active RA after initiation of Enbrel To determine if the changes in circadian activity rhythms are associated with systemic inflammation in RA patients To determine changes in traditional sleep quality variables from pre-treatment to one month after Enbrel initiation in RA patients

Detailed Description
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Rheumatoid arthritis (RA) is a chronic and debilitating disease. However, the symptoms of RA show variation over the course of the day, with worsening symptoms in the morning. This worsening of symptoms in the morning is correlated with an increase in inflammation in the body. Biologic therapies, such as Enbrel (etanercept), appear to improve energy, pain and quality of life in patients with RA, and these changes may occur before a doctor is able to detect changes during the patient's physical examination. It is possible that a patient's response to biological agents can be rapidly determined by assessing circadian activity (also called rest-activity circadian rhythms or RAR). Currently, wrist actigraphy bands, which are worn for a period of time, can reliably provide information about RAR. Wrist actigraphy bands are small electronic devices worn on the wrist (similar to a watch) that records the subject's level of activity throughout the day. Studies in osteoarthritis and in rheumatoid arthritis have found subjects with joint pain to have significant differences in RAR, and disrupted RAR has been associated with disease activity. This study will provide information about 24-hour circadian activity rhythms before and after 3-4 weeks of Enbrel treatment in study subjects with active rheumatoid arthritis. The study will assess patients who are starting on Enbrel that has been prescribed by their doctor.

Official Title
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The Effects of Biologic Therapy With Disease Activity and Circadian Rhythm

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 6/28 tender and 6/28 swollen joints (e.g. active rheumatoid arthritis) CRP ≥ 1.5mg/L Insufficient response or intolerance to ≥1 disease modifying anti-rheumatic drug (DMARD) which must include methotrexate or hydroxychloroquine, or sulfasalazine or leflunomide and at stable dose for 4 weeks If taking Glucocorticoids, stable dose from 0-10mg a day for 2 weeks, and remain stable for the 4 week study Appropriate to start on a biologic agent for RA, as determined by patient's physician. Exclusion Criteria: Prior use of a biologic agent for 4 weeks prior to the study Evidence of positive tuberculosis (TB) test, purified protein derivative (PPD) or Quantiferon or prophylactic treatment instituted 4 weeks before study, or hepatitis B core antibody No medical condition that would prevent completion of the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Etanercept|Circadian activity rhythm parameters will be evaluated for 7 days prior to Enbrel treatment through 7 days after initiation of Enbrel treatment and again 28-35 days after the second Enbrel treatment.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in pseudo F-statistic | indicator of overall robustness of circadian rhythm | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in acrophase | time of daily peak circadian activity | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in mesor | mean circadian rhythm | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in amplitude | indicator of strength of circadian rhythm | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in Disease Activity Score (DAS) | RA disease severity | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in sleep efficiency as assessed by wrist actigraphy | an index of sleep fragmentation, percentage (%) of time spend sleeping after lights off | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in general health visual analogue scale (VAS) | subject's general health | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in C-reactive protein (CRP) | systemic inflammation | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in rheumatoid factor (RF) | measures amount of rheumatoid factor present in the blood | 7 days before, 7 days after and 28-35 days after Enbrel treatment | 
| change in sleep duration as assessed by wrist actigraphy | how long (minutes) the subject sleeps 24 hour period | 7 days before, 7 days after and 28-35 days after Enbrel treatment |