Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy

October 26, 2017 updated by: Michael Irwin, MD, University of California, Los Angeles

Sleep & Immune Mechanisms in Rheumatoid Arthritis: Remicade Substudy

More than half of rheumatoid arthritis (RA) patients complain of sleep disturbance and this cardinal complaint is associated with fatigue, pain, and depressed mood in patient with chronic inflammatory disorder. Despite the frequency of this complaint, there is limited efforts to evaluate sleep or the abnormal increases in the expression of pro-inflammatory cytokines play a key role in the progression of RA, we hypothesize that the cytokine network is one physiological system that is associated with sleep disturbances in RA patients. Pro-inflammatory cytokines signal the central nervous system and are associated with increased symptoms of pain, fatigue, and depressed mood in rheumatic patients. The specific aims of the study are to examine the contribution of cytokines on sleep by administering a TNF antagonist vs. placebo to probe the action of pro-inflammatory cytokines on sleep in RA Patients. Examination of sleep and its consequences for pro-inflammatory cytokine activity within the framework of an observational and experimental research design will have implications for understanding the psycho-biological mechanisms that link sleep and the clinical manifestations of RA. Results from this study will guide the developments of interventions that target disordered sleep with potential effects on disability in RA.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Abnormal sleep is reported by more than half of rheumatoid arthritis patients, in addition to the traditional symptoms associated with the disease, such as morning stiffness, pain, and functional debility. When recording brain activity during sleep using electroencephalography or EEG. Sleep abnormalities have been found independent of pain and thus the mechanisms to account for disordered sleep in this population are unknown. The immune system, via pro-inflammatory cytokines, plays a major role in the development of rheumatoid arthritis. Pro-inflammatory cytokines are molecules that act as signals to stimulate activity of different arms of the immune system. New medications such as remicade (infliximab) have been developed which slow disease activity by blocking the activity of these pro-inflammatory cytokines. This is done by binding to the cytokine TNF and rendering it biologically inactive. Pro-inflammatory cytokines also appear to play a role in sleep. A number of basic and human studies have found that cytokines and sleep exhibit a bi-directional relationship. However, no study to date has explored this relationship in a rheumatoid arthritis population. Thus, this research study has the potential to test whether cytokines influence sleep in rheumatoid arthritis. We will determine if a single dose of a pro-inflammatory cytokine blocking medication (remicade) affects sleep in rheumatoid arthritis patients. Interested participants will undergo an eligibility interview to review in-depth subject participation, RA diagnosis, written Consent. Following eligibility, patients will undergo a single overnight sleep assessment lasting four nights at the General Clinical Research Center. After the adaption and baseline nights, on day 3, patients will be randomized to receive either 10 mg/kg of remicade or placebo and their sleep will be subsequently monitored for two additional nights ( post-infusion 1 and post-infusion 2).

Study Type

Interventional

Enrollment (Actual)

20

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 900095
        • University of California, Los Angeles, General Clinical Research Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Rheumatoid arthritis patients will meet American College of Rheumatology revised criteria (Arnett, Edworthy et al. 1988). This requires at least four of the following seven criteria: 1) morning joint stiffness; 2) arthritis in 3 or more joint areas; 3) arthritis of hand joints; 4) symmetric arthritis; 5) rheumatoid nodules; 6) presence of serum rheumatoid factor and 7) changes on posteroanterior hand and wrist radiographs. In addition, criteria 1-4 must be present for at least four weeks. Subjects must be between 18 and 85 years of age.
  2. If rheumatoid arthritis patients are receiving treatment with traditional disease modifying antirheumatic drugs (DMARD), such as methotrexate, sulfasalazine or hydroxychloroquine, they must be on a stable regime for one month before study and stable throughout study.
  3. If rheumatoid arthritis patients have received treatment with a TNF antagonist or other biologic medication, they must be drug free for greater than 3 months.

Exclusion Criteria:

  1. Steroids - Individuals currently taking greater than an equivalent of 10 mg of prednisone will be excluded given the potent anti-inflammatory effects of such medications.
  2. Opioids - Individuals using multiple daily dosage schedule of opioid agents such as oxycodone (Percocet), hydrocodone (Vicodin), morphine, Dilaudid will be excluded.
  3. Co-morbid medical disorders - the presence of active unstable and uncontrolled co-morbid medical conditions such as diabetes, cardiovascular diseases, and cancer will be exclusionary criteria. In particular, individuals with co-morbid inflammatory disorders such as Crohn's disease and ulcerative colitis and other autoimmune disorders will be excluded. Any uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or put the study participant at undue risk will also be considered exclusionary criteria.
  4. Chronic infections - individuals with chronic infections will also be excluded because of effects on immune markers measured in study.
  5. Co-morbid pain disorders - individuals with co-morbid pain disorders such as fibromyalgia will also be excluded. Individuals with fibromyalgia have been found to have sleep abnormalities as well as daytime fatigue and pain and thus could confound findings.
  6. Psychiatric disorders - current conditions such as major depressive disorder, bipolar disorder and risk for suicide will also be considered exclusionary criteria.
  7. Gender-based criteria - pregnant or breast-feeding women will also be excluded because of their effects on neuroendocrine systems and sleep

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: Placebo
Placebo-participant will receive placebo saline solution via IV route.
Drug: Remicade
Remicade/ Infliximab Study Material 10mg/kg Total Volume=250cc in saline I.V. route.
Other Names:
  • Infliximab
ACTIVE_COMPARATOR: Remicade
Remicade-Participant will be given 10 mg/kg of drug via IV route.
Drug: Remicade
Remicade/ Infliximab Study Material 10mg/kg Total Volume=250cc in saline I.V. route.
Other Names:
  • Infliximab

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Slow Wave Sleep
Time Frame: Post-infusion day 2
Slow wave sleep in minutes at post-infusion day 2 in placebo vs. remicade
Post-infusion day 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cellular Inflammation
Time Frame: Post-infusion day 2
Percentage of monocytes producing interleukin-6 at post-infusion day 2 in placebo vs. remicade
Post-infusion day 2

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, Los Angeles

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2008

Primary Completion (ACTUAL)

April 1, 2011

Study Completion (ACTUAL)

April 1, 2011

Study Registration Dates

First Submitted

July 28, 2009

First Submitted That Met QC Criteria

July 28, 2009

First Posted (ESTIMATE)

July 29, 2009

Study Record Updates

Last Update Posted (ACTUAL)

December 2, 2017

Last Update Submitted That Met QC Criteria

October 26, 2017

Last Verified

October 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NHLBI RO1 HL079955

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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