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Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy

Primary Purpose

Rheumatoid Arthritis

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Remicade

About this trial

This is an interventional basic science trial for Rheumatoid Arthritis focused on measuring Rheumatoid Arthritis

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
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.
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:

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.
Opioids - Individuals using multiple daily dosage schedule of opioid agents such as oxycodone (Percocet), hydrocodone (Vicodin), morphine, Dilaudid will be excluded.
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.
Chronic infections - individuals with chronic infections will also be excluded because of effects on immune markers measured in study.
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.
Psychiatric disorders - current conditions such as major depressive disorder, bipolar disorder and risk for suicide will also be considered exclusionary criteria.
Gender-based criteria - pregnant or breast-feeding women will also be excluded because of their effects on neuroendocrine systems and sleep

Sites / Locations

University of California, Los Angeles, General Clinical Research Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

Remicade

Arm Description

Placebo-participant will receive placebo saline solution via IV route.

Remicade-Participant will be given 10 mg/kg of drug via IV route.

Outcomes

Primary Outcome Measures

Slow Wave Sleep

Slow wave sleep in minutes at post-infusion day 2 in placebo vs. remicade

Secondary Outcome Measures

Cellular Inflammation

Percentage of monocytes producing interleukin-6 at post-infusion day 2 in placebo vs. remicade

Full Information

NCT ID

NCT00948610

First Posted

July 28, 2009

Last Updated

October 26, 2017

Sponsor

University of California, Los Angeles

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT00948610

Brief Title

Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy

Official Title

Sleep & Immune Mechanisms in Rheumatoid Arthritis: Remicade Substudy

Study Type

Interventional

2. Study Status

Record Verification Date

October 2017

Overall Recruitment Status

Completed

Study Start Date

November 2008 (undefined)

Primary Completion Date

April 2011 (Actual)

Study Completion Date

April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of California, Los Angeles

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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 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.

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Rheumatoid Arthritis

Keywords

Rheumatoid Arthritis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantOutcomes Assessor

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Placebo-participant will receive placebo saline solution via IV route.

Arm Title

Remicade

Arm Type

Active Comparator

Arm Description

Remicade-Participant will be given 10 mg/kg of drug via IV route.

Intervention Type

Drug

Intervention Name(s)

Remicade

Other Intervention Name(s)

Infliximab

Intervention Description

Remicade/ Infliximab Study Material 10mg/kg Total Volume=250cc in saline I.V. route.

Primary Outcome Measure Information:

Title

Slow Wave Sleep

Description

Slow wave sleep in minutes at post-infusion day 2 in placebo vs. remicade

Time Frame

Post-infusion day 2

Secondary Outcome Measure Information:

Title

Cellular Inflammation

Description

Percentage of monocytes producing interleukin-6 at post-infusion day 2 in placebo vs. remicade

Time Frame

Post-infusion day 2

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. 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. 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: 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. Opioids - Individuals using multiple daily dosage schedule of opioid agents such as oxycodone (Percocet), hydrocodone (Vicodin), morphine, Dilaudid will be excluded. 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. Chronic infections - individuals with chronic infections will also be excluded because of effects on immune markers measured in study. 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. Psychiatric disorders - current conditions such as major depressive disorder, bipolar disorder and risk for suicide will also be considered exclusionary criteria. Gender-based criteria - pregnant or breast-feeding women will also be excluded because of their effects on neuroendocrine systems and sleep

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Michael Irwin, MD

Organizational Affiliation

University of California, Los Angeles

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of California, Los Angeles, General Clinical Research Center

City

Los Angeles

State/Province

California

ZIP/Postal Code

900095

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

18561896

Citation

Irwin MR, Wang M, Ribeiro D, Cho HJ, Olmstead R, Breen EC, Martinez-Maza O, Cole S. Sleep loss activates cellular inflammatory signaling. Biol Psychiatry. 2008 Sep 15;64(6):538-40. doi: 10.1016/j.biopsych.2008.05.004. Epub 2008 Jun 17.

Results Reference

background

PubMed Identifier

19520155

Citation

Irwin MR, Carrillo C, Olmstead R. Sleep loss activates cellular markers of inflammation: sex differences. Brain Behav Immun. 2010 Jan;24(1):54-7. doi: 10.1016/j.bbi.2009.06.001. Epub 2009 Jun 9.

Results Reference

background

PubMed Identifier

19590742

Citation

Irwin MR, Davis M, Zautra A. Behavioral Comorbidities in Rheumatoid Arthritis: A Psychoneuroimmunological Perspective. Psychiatr Times. 2008 Aug 1;25(9):1. No abstract available.

Results Reference

background

PubMed Identifier

17706915

Citation

Davis MC, Zautra AJ, Younger J, Motivala SJ, Attrep J, Irwin MR. Chronic stress and regulation of cellular markers of inflammation in rheumatoid arthritis: implications for fatigue. Brain Behav Immun. 2008 Jan;22(1):24-32. doi: 10.1016/j.bbi.2007.06.013. Epub 2007 Aug 15.

Results Reference

background

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Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy

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