Clinical trial NCT03178955: Circadian RA Study in Rheumatoid Arthritis Subjects
Official title: The Effects of Biologic Therapy With Disease Activity and Circadian Rhythm
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Rheumatoid Arthritis
Lead sponsor: University of California, Davis
Sponsor class: OTHER
First posted: 2017-06-07
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Investigators will utilized the UC Davis Cohort Discovery Tool to identify patients within the UC Davis healthcare system who meet the inclusion/exclusion criteria. Investigators will then contact the patients' primary care provider and request permission to contact the patient about the study. Investigators will contact potential subjects to determine their interest and complete screenings by phone. Additionally, investigators plan to advertise the study on flyers posted in the hospital and community, as well as online notices on the Center for Musculoskeletal Health website.

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: change in pseudo F-statistic
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in acrophase
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in mesor
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in amplitude
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in Disease Activity Score (DAS)
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
Secondary outcomes:
measure: change in sleep efficiency as assessed by wrist actigraphy
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in general health visual analogue scale (VAS)
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in C-reactive protein (CRP)
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in rheumatoid factor (RF)
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
measure: change in sleep duration as assessed by wrist actigraphy
timeFrame: 7 days before, 7 days after and 28-35 days after Enbrel treatment
Other outcomes:
Locations:
city: Sacramento
country: United States
facility: UC Davis Center for Musculoskeletal Health
state: California
Study officials:
affiliation: UC Davis Center for Musculoskeletal Health
name: Nancy E Lane, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: California Pacific Medical Center Research Institute
name: Katie Stone, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: