Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy
Summary
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 complain, there is limited efforts to evaluate sleep or the abnormal increases in the expression of proinflamatory 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. Proinflamatory cytokines signal the central nervous system and are associated with increased symptoms of pain, fatigue, and depressed mood in rheumatic patients. Moreover, sleep loss is coincident with alterations in sympathetic tone, which is thought to contribute to increases of proinflammatory cytokine activity. 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 proinflammatory cytokines on sleep in RA Patients. Examination of sleep and its consequences for autonomic functioning and proinflamatory 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.
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. Proinflammatory 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). Participants will then be follow-up for three months after either remicade or placebo infusions. In this way, the effects of blocking pro-inflammatory cytokines can be examined for sleep, morning stiffness, pain and fatigue.
Study Design
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Basic Science
Conditions
Rheumatoid Arthritis
Intervention
Remicade
Location
University of California, Los Angeles, General Clinical Research Center
Los Angeles
California
United States
900095
Status
Recruiting
Source
University of California, Los Angeles
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00948610
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Arthritis, Juvenile Rheumatoid
Rheumatoid arthritis of children occurring in three major subtypes defined by the symptoms present during the first six months following onset: systemic-onset (Still's Disease, Juvenile-Onset), polyarticular-onset, and pauciarticular-onset. Adult-onset cases of Still's disease (STILL'S DISEASE, ADULT-ONSET) are also known. Only one subtype of juvenile rheumatoid arthritis (polyarticular-onset, rheumatoid factor-positive) clinically resembles adult rheumatoid arthritis and is considered its childhood equivalent.
Gold Sodium Thiomalate
A variable mixture of the mono- and disodium salts of gold thiomalic acid used mainly for its anti-inflammatory action in the treatment of rheumatoid arthritis. It is most effective in active progressive rheumatoid arthritis and of little or no value in the presence of extensive deformities or in the treatment of other forms of arthritis.
Still's Disease, Adult-onset
Systemic-onset rheumatoid arthritis in adults. It differs from classical rheumatoid arthritis in that it is more often marked by acute febrile onset, and generalized lymphadenopathy and hepatosplenomegaly are more prominent.
Rheumatoid Factor
Antibodies found in adult RHEUMATOID ARTHRITIS patients that are directed against GAMMA-CHAIN IMMUNOGLOBULINS.
Phenylbutazone
A butyl-diphenyl-pyrazolidinedione that has anti-inflammatory, antipyretic, and analgesic activities. It has been used in ANKYLOSING SPONDYLITIS; RHEUMATOID ARTHRITIS; and REACTIVE ARTHRITIS.
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