Rheumatoid Arthritis Clinical Trial
Official title:
Reduction of Daily Sitting Time in Patients With Rheumatoid Arthritis. A Randomized Controlled Trial.
Background:
In recent years there has been a growing interest in sedentary behaviour defined as
activities performed in sitting or lying position during waking hours. Sedentary behaviour
has been recognised as an independent risk factor for cardiovascular diseases and mortality.
A few intervention studies in older sedentary people and in overweight or obese adults have
demonstrated, that daily sitting time can be reduced through behavioural intervention.
Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular diseases,
partly caused by the rheumatic disease itself but also because of physical inactivity.
Studies have documented a positive effect of increasing physical activity on pain and
physical functioning in patients with RA. However, the studies also show, that the patients
find it difficult to maintain the increased physical activity levels over time. Previous
studies suggest that in promoting health among patients with mobility disability should not
solely focus on increasing moderate to vigorous physical activity but also target reduction
of sedentary behaviour and increase of light physical activity. In the present study we will
focus on reduction of daily sitting time and increase of light physical activity as this
approach may prove more feasible for patients with RA.
Objectives and hypothesises:
We hypothesise, that sedentary behaviour can be reduced in patients with RA through a
behavioural lifestyle change. In addition, we hypothesize, that reduction of daily sitting
time can have a positive effect on symptoms and general health in patients with RA.
The primary objective of the present intervention study is to investigate the effect of a
motivational counselling intervention on daily sitting time in adult men and women with RA.
Furthermore we want to investigate whether a reduction in daily sitting time is related to
reduction in pain and fatigue, reduced weight and waist circumference and improved quality
of life, physical function and improved cardiovascular biomarker levels (cholesterol and
blood pressure).
Study setting and allocation:
In total, 150 participants will be recruited from the rheumatology outpatient clinic at
Glostrup University Hospital, Denmark. The participants will be allocated to either an
intervention group (75) or a control group (75).
Intervention:
The intervention aims to support and strengthen the participants' belief in their own
ability to reduce their daily sitting time. The intervention will include 1) three
individual motivational counselling sessions (60-90 minutes), conducted by one of four
project nurses in combination with 2)Individual Short Text Messages (SMS). The counselling
sessions will focus on information about the positive health effects of reducing daily
sitting time and the participants' own goals of reducing their sitting time. Based on the
goals the participants will receive weekly SMS reminders.
Data collection:
Measurements on all participants will be done four times during 22 months; 1) at baseline,
2) 16 weeks after start (by the end of the intervention), 3) six months after end of
intervention and 4) 18 months after end of intervention. At each of the four visits the
participants fill in questionnaires regarding demographics, lifestyle, daily sitting time,
physical activity, physical function, pain , fatigue and quality of life. Furthermore, two
occupational therapists will measure the participants' blood pressure, height, weight and
waist circumference. At the same time a little monitor will be placed on the participants'
thigh, which they will carry for seven days. The monitor measures the participants' physical
activity level. The four measurements also include a blood sample from the participants in
order to measure cholesterol levels.
Background and rationale:
Physical inactivity is an established risk factor for chronic disease and premature death.
In addition to physical inactivity sedentary behaviour has been recognised as a distinct and
independent risk factor for cardio metabolic morbidity and mortality in an increasing number
of population-based observational studies. Patients with rheumatoid arthritis (RA) have an
increased risk for cardio metabolic disease and pre-mature death. The increased risk is,
partly caused by the chronic autoimmune rheumatic disease itself and partly to traditional
risk factors e.g. hyperlipidemia and hypertension, but can also be attributed to physical
inactivity. In Denmark 67 % of patients with RA do not comply with public health
recommendations for daily moderate and vigorous physical activity (MVPA), and equivalent
proportions are found in Germany (68 %) and the United Kingdom (67 %). Everyday life of
patients suffering from RA is periodically influenced by high disease activity (flares) with
symptoms such as swelling and stiffness of the joints accompanied by intense pain, leading
to severe limitations in physical functioning and potential progressive joint destruction.
Intervention studies in patients with RA have documented a positive effect of exercise on
pain and physical functioning. However, studies have also demonstrated that exercise and
increased activity levels are difficult to maintain over time. Pain has been identified as a
main barrier against adaptation and maintenance of a physically activity lifestyle.
Sedentary behaviour can be defined as low metabolic cost activities performed in sitting or
reclining positions during waking hours. Sedentary behaviour has become increasingly
prevalent in modern society, and recent population studies using self-reported
questionnaires estimate daily sitting time of 8-9 hours per day, corresponding to 50-60 % of
waking hours in adult general population samples. Likewise, an American population-based
study among 4.757 adults, found an objectively measured daily sitting time of 8.44 hours. A
few studies have monitored objectively measured sitting time in patients with chronic
disease and mobility disability, and these studies generally find that higher proportions of
the day are spent sitting among people with various types of mobility disability, i.e.
stroke (86-88 % of waking hours), multiple sclerosis (75-85 % of waking hours) and
Parkinson's disease (76 % of waking hours). However, to our knowledge no studies have
reported objectively measured sitting time in patients with RA. A review from 2011 suggests
that aiming to increase PA levels among patients with mobility disability should not solely
focus on increasing MVPA, but should also target reduction of sedentary time and increase of
light intensity activity, as this approach may prove feasible for improving health and
well-being among sedentary patients with chronic disease and mobility limitation.
A few short term intervention studies in older people, and in overweight or obese adults
have demonstrated that sedentary behaviour can be reduced through behavioural intervention
and that physical activity energy expenditure may be increased by reduction of TV-viewing
time. All studies applied objective measures of sitting time.
Objectives:
We hypothesize that sedentary behaviour can be reduced in patients with RA through
behavioural lifestyle change. The primary objective of the present randomised trial is to
investigate the effect of an individually tailored, theory-based motivational counselling
intervention on daily sitting time in patients with rheumatoid arthritis and with sitting
time more than 5 hours a day. The secondary objectives are to explore whether a reduction in
daily sitting time is related to reduction in pain and fatigue, improved health-related
quality of life (HRQOL), self-reported physical function and self-efficacy and improved
cardiovascular biomarker levels, and to assess the cost-effectiveness of the intervention.
Design:
The 'Joint Resources' sedentary behaviour intervention study (JR-Sedentary Behaviour) is a
randomised, controlled, observer-blinded trial with two parallel groups and a primary
endpoint of changes in objectively measured daily sitting time.
Study setting:
Patients will be recruited from lists of patients with RA from the rheumatology outpatient
clinic at Copenhagen University Hospital, Glostrup, the Capital Region of Denmark
(approximately 2000 patients annually).
Recruitment, screening and participants:
The patients' medical records will be screened for diagnosis code and the latest HAQ-score.
Potentially eligible patients will receive a letter with an invitation together with written
information about the study and a folder with basic information about trials and personal
rights in accordance with the guidelines of the Danish Scientific Ethical Committees. A few
days later the daily project leader will call them and ask about their interest in
participating in the study. If they are interested they must answer two "screening
questions" on 1) self-reported daily sitting time during leisure and work, and 2)
self-reported participation in vigorous physical activity (both questions are from The
Physical Activity Scale (PAS 2.1)). If eligible the patients will be invited to an
information session with the project leader. It will be possible for the patients to sign
the consent form immediately following the session or alternatively during the following two
days.
Sample size:
Calculation of sample size was based on data from a completed feasibility study (publication
under preparation) in which the total daily time in patients with RA was objectively
measured with ActivePAL. The daily average sitting time was 10.13±1.7 hours (mean±SD). In
the present intervention study we expect a reduction in average daily sitting time of 50
minutes in the intervention group. This estimate is based on an American pilot study from
2012 on obese office workers who reduced their daily sitting time by 48 minutes as a result
of the intervention. Based on results from that study, a significance level α = 5%, and a
power of 80% we need to include 62 patients in each of the groups. To compensate for
attrition we aim to recruit 75 patients in each group.
Randomization and blinding:
Immediately following the baseline measurements randomization to either (A) intervention
group (N = 75) or (B) control group (N = 75 ) will be performed via computer-generated
"random numbers" for each of the two groups (blocks of 10 patients). Patients will be
informed by the project leader about their group allocation one week after baseline
measurements. All measurements are conducted by two occupational therapists who will be
blinded to group allocation.
Intervention:
The intervention will include 1) Individual motivational counselling including handouts of
four key messages regarding in reduction of daily sitting time in combination with 2)
Individual Short Text Message (SMS) reminders.
1. Individual motivational counselling The intervention consists of three individual
motivational counselling (60-90 minutes) sessions, conducted by one of four nurses or
occupational therapists, who are trained to conduct this specific intervention. The
first counselling will take place immediately after randomization and allocation to the
intervention group, the second counselling two weeks after, and the third counselling
ten weeks after the first counselling.
Contents of motivational counselling The intervention will focus on individual goal
setting and self-efficacy, where participants describe their everyday life in terms of
sitting time and decide how to reduce their daily sitting time, how to overcome
barriers and what goal, in terms of reducing sitting time, they aim for. Motivational
counselling techniques will be used.
First, project staff will introduce the patients to the possible benefits of reducing
their daily sitting time. Secondly, project staff will ask the patients to describe
their typical day in order to identify resources and barriers for reduction of daily
sitting time and discuss possible solutions to overcome barriers and use resources.
Thirdly, the patients set their own goals for reduction of daily sitting time using a
"catalogue of ideas", which contains proposals to reduce and create breaks in sitting
time. Specific proposals to reduce daily sitting time are for example to stand up
during phone conversations or TV-watching, get up frequently to go to the printer, get
up at least once every half hour and walk around, get up to change the TV channel, make
one cup of coffee each time. During the motivational counselling session number two and
three patients own goals will be evaluated, new goals will be set and possible solution
strategies will be addressed. The patients' motivation and confidence in their own
ability to change will be in focus in the last two sessions.
The intervention program focuses on 4 key messages or themes, including ideas and
suggestions for reduction of sitting time, which are written in booklets that will be
handed to the patients at each session. The four key messages are: 1) Reduce daily
TV-viewing, 2) Substitute sitting with standing when possible - at work and/or at home,
3) Break up prolonged sitting - by standing up frequently and 4) Maximum 30 minutes of
sitting per episode.
2. Individual SMS reminders
Based on the patients' own individually goals the patients decide how many weekly SMS
reminders they want to receive during the 16-week intervention period and at what time of
the day. Examples of SMS text messages are shown below:
- Hello X. Raise from your table stand-up and allow gravity to assist your lunch to
digest. Bonus: You burn more energy when you stand.
- Hi X. Regard vacuum cleaning as a free fitness hour. Put music in your ears and do not
stop until both the list and the cleaning is done.
- Hi X. You have some truly privileged colleagues who in this afternoon will be able to
see you stand by your table. Show them how to do it, and they might follow your good
example.
- Hey X. Put the remote control next to the TV if you turn on the television today. Every
time you change the channel your entire body gets some exercise.
Control group:
The control group will be encouraged to maintain their usual lifestyle during the 16-week
intervention period.
Participant timeline:
The trial will last 22 months including a 16-week intervention and an 18 months follow-up.
Data collection:
Measurements will be done four times during the 22 months 1) at baseline; 2) by end of the
intervention (16 weeks after intervention start); 3) six months after the intervention ends
and finally (4) 18 months after the intervention ends. At each time patients fill in
self-complete questionnaires regarding demographics, lifestyle, sitting time at work and in
leisure time, physical activity, physical function, pain, fatigue, health-related quality of
life (HRQoL) and self-efficacy. Subsequently, blood pressure, height, weight, waist
circumference are measured by two occupational therapists. Blood sampling tests will be
taken at Department of Diagnostics, Division of Clinical Biochemistry, Copenhagen University
Hospital, Glostrup and store the tests. Baseline demographic characteristics of patients are
collected via self-reported questionnaire (using iPad). The two occupational therapists also
put on an ActivPAL monitor, which objectively measures the participants' physical activity
level for a period of seven days. One week (7 days) after baseline measurements the
participant will return to the hospital for removal of the ActivPAL. At the same time they
will be informed by TT about the group allocation. One week after each of the follow up
measurement the patients will return the ActivPAL in a closed envelope. During each 7
day-period with ActivPal the patients fill in a diary about their non-wear-and sleep time in
order to isolate their sitting time from non-wear and sleeping. The patients will be
recruited from the DANBIO database, a nationwide registry that has included > 25,000
patients with inflammatory arthritis in a longitudinal observational cohort. At each medical
visit in the outpatient clinic, the treating rheumatologist registers information in DANBIO
including data regarding disease characteristics (e.g. patient-reported outcomes, disease
activity, functional status, disease course) and medical treatment.
Data management:
Since all data will be supplied directly by the patients and the assessors through an online
interface via an iPad, there is no risk of data loss or data distortion along the way. Data
will be stored encrypted and in unidentifiable form (using participant-numbers) in the
server at Glostrup Hospital. Standard missing data analysis will determine if unexpected
missing data due to participant drop-out are random or not.
Analysis:
Descriptive statistics and regression analyzes will be conducted. Data analyses will be
based on intention-to-treat principle . The scoring of the standardized questionnaires will
be made according to the guidelines from instrument developers.
A cost analysis will report the resource use and cost of the intervention. For both the
intervention and control group survey and registry based data on resource use including
services provided in the health care sector (primary and secondary care) and pharmaceuticals
will be aggregated for each individual in intervals determined by the time of data
collection. Cost data will be interpolated to total cost for the whole observation period
(18 months). The aggregated cost data will be analyzed as costs attributable to the
intervention (i.e. difference in difference) and reported as mean values with 95%
(bootstrap) confidence intervals. Due to the non-normal distribution of cost data
generalized linear models will be employed with appropriate choice of link function.
The analysis of cost-effectiveness will compare the observed gain in QALY (HRQOL over 18
months) with the observed incremental cost (over 18 months) by estimating incremental
cost-effectiveness ratios (ICER). To express statistical uncertainty in the ICER estimates
acceptability curves will be developed to express the likelihood of the intervention being
cost-effective at various QALY threshold values.
The regression model will allow controlling for the baseline value of the study endpoints
and other confounding variables that may impact changes in sedentary behavior (e.g. age,
gender). In addition, a drop-out analysis will be conducted. Treatment outcomes will be
examined using mixed effect models, Bonferroni-correcting for multiple comparisons. All
analysis will be carried out with SAS statistical software 9.3.
Ethics, confidentiality and dissemination:
The trial will be performed in accordance with the Helsinki Declaration. The project has
been reviewed by the Regional Committee on Biomedical Research Ethics September 2012 as
registry based research. The study was approved by the Danish Data Protection Agency. All
formal rules and safety rules in the process from data collected for publication are
observed (Danish Data Protection Agency, Research Ethics Committee, Clinicaltrial.gov, IT
issues, etc.). Anyone who has access to the full relevant data sets (Chief Executive, all
supervisors, project staff) are familiar with the formal and safety rules. All information
collected during the course of the study will be kept strictly confidential in accordance
with Danish Data Protection Agency rules; operationally, this will include consent from the
patients.
It is planned to publish at least four scientific papers in peer reviewed journals based on
the trial .
In addition, following sources are included in the communication plan:
- Papers (scientific and popular science)
- Presentations at conferences or similar (International and National)
- Collaboration with The Danish Rheumatism Association both members and groups of
employees
Access to data:
The project group will have access to data as well as DanBio . Data generated in the trial
belong to Copenhagen University Hospital, Glostrup. The steering group to "Joint Resources"
will be involved in the case of query about access to data.
Trial status:
Recruitment for the trial is planned to start in April 2013, and will end in December 2014.
Funding:
The study is supported by grants from the Danish Rheumatism Association, the Novo Nordic
Foundation, the Lundbeck Foundation, the Research Foundation of the Capital Region of
Denmark, the Bevica Foundation, Maersk McKinney Møller Foundation, the Tryg Foundation
(external scientific review process), Glostrup Hospital, and Capital Region of Denmark. The
funders had no role in the design or management of the study.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT04226131 -
MusculRA: The Effects of Rheumatoid Arthritis on Skeletal Muscle Biomechanics
|
N/A | |
Completed |
NCT04171414 -
A Study to Evaluate Usability of Subcutaneous Auto-injector of CT-P17 in Patients With Active Rheumatoid Arthritis
|
Phase 3 | |
Completed |
NCT02833350 -
Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
|
Phase 2 | |
Completed |
NCT04255134 -
Biologics for Rheumatoid Arthritis Pain (BIORA-PAIN)
|
Phase 4 | |
Recruiting |
NCT05615246 -
Exactech Humeral Reconstruction Prosthesis of Shoulder Arthroplasty PMCF (HRP)
|
||
Completed |
NCT03248518 -
Lessening the Impact of Fatigue in Inflammatory Rheumatic Diseases
|
N/A | |
Completed |
NCT03514355 -
MBSR in Rheumatoid Arthritis Patients With Controlled Disease But Persistent Depressive Symptoms
|
N/A | |
Recruiting |
NCT06005220 -
SBD121, a Synbiotic Medical Food for RA Management
|
N/A | |
Recruiting |
NCT05451615 -
Efficacy and Safety of Abatacept Combined With JAK Inhibitor for Refractory Rheumatoid Arthritis
|
Phase 3 | |
Completed |
NCT05054920 -
Eccentric Versus Concentric Exercises for Rotator Cuff Tendinopathy in Patients With Rheumatoid Arthritis
|
N/A | |
Completed |
NCT02037737 -
Impact and Use of Abatacept IV for Rheumatoid Arthritis in Real Life Setting
|
N/A | |
Recruiting |
NCT04079374 -
Comparative Efficacy, Safety and Immunogenicity Study of Etanercept and Enbrel
|
Phase 3 | |
Completed |
NCT02504268 -
Effects of Abatacept in Patients With Early Rheumatoid Arthritis
|
Phase 3 | |
Recruiting |
NCT05496855 -
Remote Care in People With Rheumatoid Arthritis
|
N/A | |
Completed |
NCT05051943 -
A Study of the Real-world Use of an Adalimumab Biosimilar and Evaluation of Nutritional Status on the Therapeutic Response
|
||
Recruiting |
NCT06103773 -
A Study of Single and Multiple Oral Doses of TollB-001
|
Phase 1 | |
Recruiting |
NCT06031415 -
Study of GS-0272 in Participants With Rheumatoid Arthritis
|
Phase 1 | |
Completed |
NCT05999266 -
The Cartilage and Muscle Thickness on Knee Pain in Patients With Rheumatoid Arthritis
|
||
Recruiting |
NCT05302934 -
Evaluation of the PHENO4U Data Platform in Patients Undergoing Total Knee Arthroplasty
|
||
Recruiting |
NCT04169100 -
Novel Form of Acquired Long QT Syndrome
|
Phase 4 |