Rheumatoid ArthritisNCT00948610
Sleep and Immunity in Rheumatoid Arthritis : Remicade Substudy
A study testing Remicade in people with Rheumatoid Arthritis, run by University of California, Los Angeles at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Rheumatoid Arthritis
- What is being tested?
- Remicade
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2008to Apr 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California, Los Angeles, General Clinical Research Center
Los Angeles, California, 900095
About this study
Official title: 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.
Read the 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).
- Conditions
- Rheumatoid Arthritis
- Being tested
- Remicade
- Keywords
- Rheumatoid Arthritis
- Medical subject headings
- Arthritis, Rheumatoid
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RemicadeDrug
Also called Infliximab
Remicade/ Infliximab Study Material 10mg/kg Total Volume=250cc in saline I.V. route.
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo-participant will receive placebo saline solution via IV route. Receives: Drug: Remicade |
| Remicade | Active comparator | Remicade-Participant will be given 10 mg/kg of drug via IV route. Receives: Drug: Remicade |
What is being measured
The primary outcome is the main question the study is designed to answer.
Slow Wave Sleep
Slow wave sleep in minutes at post-infusion day 2 in placebo vs. remicade
Measured: Post-infusion day 2
Secondary outcomes (1)
Cellular Inflammation
Percentage of monocytes producing interleukin-6 at post-infusion day 2 in placebo vs. remicade
Measured: Post-infusion day 2
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2009 (estimated)
- Study startNov 2008
- Primary completionApr 2011
- Study completionApr 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Rheumatoid ArthritisStudies of the same condition, open and under way.
- More trials run by University of California, Los AngelesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, Los Angeles
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Michael Irwin, MD, University of California, Los Angeles
- Investigators
- Michael Irwin, MD, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00948610
- Sponsor's protocol ID
- NHLBI RO1 HL079955
- Other IDs
- NHLBI RO1 HL079955
- Status last verified
- Oct 2017
- First submitted
- 28 Jul 2009
- Last updated
- 2 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 18561896Irwin 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.
PubMed 19520155Irwin MR, Davis M, Zautra A. Behavioral Comorbidities in Rheumatoid Arthritis: A Psychoneuroimmunological Perspective. Psychiatr Times. 2008 Aug 1;25(9):1. No abstract available.
PubMed 19590742Davis 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.
PubMed 17706915
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sleep & Immune Mechanisms in Rheumatoid Arthritis: Remicade Substudy
- ClinicalTrials.gov ID
- NCT00948610
- Acronym / sponsor ID
- NHLBI RO1 HL079955
- Conditions
- Rheumatoid Arthritis
- Keywords
- Rheumatoid Arthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of California, Los AngelesUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Nov 2008
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 29 Jul 2009 (estimated)
- Results
- Posted 12 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: RemicadePlacebo-participant will receive placebo saline solution via IV route. |
| Remicade | Active comparator | Drug: RemicadeRemicade-Participant will be given 10 mg/kg of drug via IV route. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RemicadeAlso: InfliximabRemicade/ Infliximab Study Material 10mg/kg Total Volume=250cc in saline I.V. route. | Drug | Placebo, Remicade |
Primary outcome
Slow Wave Sleep
Time frame: Post-infusion day 2
Slow wave sleep in minutes at post-infusion day 2 in placebo vs. remicade
1 secondary outcome
Cellular Inflammation
Time frame: Post-infusion day 2
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 18561896Irwin 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.
- Background: PubMed 19520155Irwin 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.
- Background: PubMed 19590742Irwin MR, Davis M, Zautra A. Behavioral Comorbidities in Rheumatoid Arthritis: A Psychoneuroimmunological Perspective. Psychiatr Times. 2008 Aug 1;25(9):1. No abstract available.
- Background: PubMed 17706915Davis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Michael Irwin, MD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Remicade in people with Rheumatoid Arthritis, run by University of California, Los Angeles at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Sep 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Slow Wave Sleep (time frame: Post-infusion day 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00948610, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2017.