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Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Michael Irwin, M.D., University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00948610
First received: July 28, 2009
Last updated: June 26, 2012
Last verified: June 2012
  Purpose

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.


Condition Intervention
Rheumatoid Arthritis
Drug: Remicade

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Sleep & Immune Mechanisms in Rheumatoid Arthritis: Remicade Substudy

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Changes in sleep patterns as measured by objective polysomnography and subjective report due to Remicade Infusion; Changes in daytime impairment, fatigue, mood, health function and joint count [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in measure of proinflammatory cytokine activity due to remicade infusion; Change sympathovagal function and energy balance; changes interpersonal resilience and social function [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 36
Study Start Date: November 2008
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Infliximab

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. 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.

  Eligibility

Ages Eligible for Study:   18 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 (Drewes 1999) 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948610

Locations
United States, California
University of California, Los Angeles, General Clinical Research Center
Los Angeles, California, United States, 900095
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Michael Irwin, MD University of California, Los Angeles
  More Information

Publications:
Responsible Party: Michael Irwin, M.D., Professor in Residence, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT00948610     History of Changes
Other Study ID Numbers: NHLBI RO1 HL079955, NHLBI RO1 HL079955
Study First Received: July 28, 2009
Last Updated: June 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by University of California, Los Angeles:
Rheumatoid Arthritis

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Infliximab
Analgesics
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Central Nervous System Agents
Dermatologic Agents
Gastrointestinal Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sensory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 25, 2014