Circadian RA Study in Rheumatoid Arthritis Subjects

The Effects of Biologic Therapy With Disease Activity and Circadian Rhythm

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

Study Overview

• Status: Withdrawn
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Etanercept

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Center for Musculoskeletal Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, Davis
• Investigators: Principal Investigator: Nancy E Lane, M.D., UC Davis Center for Musculoskeletal Health; Principal Investigator: Katie Stone, Ph.D., California Pacific Medical Center Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): April 16, 2019
• Study Completion (Anticipated): August 16, 2019

Study Registration Dates

• First Submitted: June 2, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (Actual): June 7, 2017

Study Record Updates

• Last Update Posted (Actual): June 14, 2019
• Last Update Submitted That Met QC Criteria: June 12, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 1023265

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes