Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01534871 |
Other study ID # |
CDHA_NB_SG-2012 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
October 2, 2013 |
Est. completion date |
October 22, 2022 |
Study information
Verified date |
November 2022 |
Source |
Nova Scotia Health Authority |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects approximately 1% of
all Canadians. RA is associated with a higher rate of disease and death as well as a
decreased life expectancy. Changes in death rates and life expectancy are mainly the result
of an increased frequency of cardiovascular disease (CVD). The increase in CVD frequency is
primarily attributable to accelerated atherosclerosis. It is believed that elevated levels of
inflammation, which are characteristic of RA, play a key role in accelerated rate of CVD in
RA patients. Thus, inflammation is considered a primary risk factor for CVD in RA patients.
Interestingly, despite a better understanding of the relationship between RA and CVD and
improved treatment for RA patients the death rate in RA population continues to increase.
Thus, there is an immediate need to develop treatment strategies to reduce the risk of CVD
associated with inflammation in the RA population.
Exercise is commonly used to reduce the risk of CVD. Preventative exercise programs are often
offered as part of cardiac rehabilitation (CR) programs. These programs help patients modify
CVD risk factors, improve physical capacity and decrease CVD risk. Studies also suggest that
CR programs decrease levels of inflammation. Since RA patients have an elevated risk for CVD,
which is primarily attributed to increased levels of inflammation, they are prime candidates
for CR programs. However, RA patients are very rarely referred to CR programs. Thus, there is
a lack of information regarding the effects of CR on RA patients. Thus studies are needed to
determine whether CR modifies levels of inflammation and decreases CVD risk in RA patients.
Therefore, the purpose of this study is to determine the effects of a 12-week standardized
cardiac rehabilitation exercise program on systemic inflammation and CVD risk in individuals
with RA. Specifically, this study will characterize the effects of a community based CR
exercise program on systemic markers of inflammation (proinflammatory cytokines) and global
CVD risk (Framingham risk profile) as well as the therapeutic effects of CR exercise on the
severity of RA.
This study will help to clarify the mechanism(s) by which exercise impacts CVD risk in
patients with inflammatory disease. In addition, the study will show how CR may benefit
patients with inflammatory disease with respect to their ability to exercise, global risk for
cardiovascular disease and quality of life.
Description:
Rheumatoid arthritis (RA) is a chronic inflammatory disease that impacts approximately 1% of
all Canadians. RA is associated with increased mortality, decreased life expectancy and
increased morbidity, which is primarily attributable to an increased risk of cardiovascular
disease (CVD). Traditional risk factors (e.g. dyslipidemia, hypertension, physical
inactivity, etc.) contribute, in part, to the elevated risk of CVD in individuals with RA.
However, the higher incidence of CVD events in RA appears to be independent of the influence
of traditional CVD risk factors. Non-traditional risk factors, such as inflammation, also
contribute to the increased risk of CVD in RA patients. In fact, when traditional CVD risk
factors and co-morbidities are controlled for in people with RA, markers of systemic
inflammation confer a significant additional risk for CV death. This suggests that systemic
inflammation significantly contributes to the increased risk of CVD in individuals with RA.
Thus, there is an immediate need to develop intervention strategies to reduce the
inflammatory mediated risk of CVD in the RA population.
One possible intervention that could be used to decrease CVD risk in RA patients is exercise.
Exercise can modify both traditional (e.g. dyslipidemia) and non-traditional (e.g.
inflammation) risk factors to decrease the risk of CVD. For patients with cardiac disease,
clinical guidelines recommend regular exercise. For this, patients are referred to cardiac
rehabilitation (CR) programs, where exercise represents the cornerstone of the program. The
goal of these programs is modify CVD risk factors, improve physical capacity and decrease CVD
risk. Thus, CR programs may offer a suitable therapeutic intervention to help decrease CVD
risk in RA patients. However, RA patients are rarely referred to CR despite their increased
risk of CVD. Thus, the effects of CR on inflammation and CVD risk in patients with RA remains
unclear.
The purpose of this study is to examine the effects of a 12-week cardiac rehabilitation
exercise program on systemic inflammation and CVD risk in individuals with RA. The specific
objectives of the study are: 1) to determine whether it is feasible for RA patients to
complete a 12-week high intensity CR exercise program, 2) examine the effects of a 12-week
standardized CR exercise program on systemic markers of inflammation in individuals with RA,
3) to examine the effects of a 12-week standardized CR exercise program on CVD risk in
individuals with RA and 4) to characterize the effects a 12-week standardized CR exercise
program on the severity of the patient's RA and their functional ability.
This study is meant to be a pilot study that will help provide insight into the therapeutic
effects of CR on inflammation and CVD risk in RA patients. Based on the results from this
preliminary work, a larger scale study will be developed to evaluate the effects of exercise
intensity on cardiovascular risk in patients with inflammatory disease as well as the effects
of exercise on decision making for pharmacological intervention (e.g. statin therapy) in this
population.
Methods:
Study Design: This pilot study is a randomized controlled study. Subjects will be randomly
assigned to one of two groups: 1) control (CON) or 2) CR program with high intensity exercise
(CRH). Outcome measures will be assessed at baseline (week-0) and post-intervention
(week-13). The primary measures include CVD risk, levels of systemic inflammation and
severity of RA. Secondary measures include weight, waist girth, resting heart rate, resting
blood pressure (BP), lipid profile, fasting glucose, aerobic fitness, physical activity (PA)
levels, functional ability, tobacco use and alcohol consumption.
Patient Screening: If the individual agrees to participate in the study, they will be asked
if they use tobacco regularly and if they are a diabetic, have their BP measured and sent for
routine blood work. Blood tests will be performed to determine the patient's lipid profile
(total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol
and triglycerides). The patient's BP, answers to the aforementioned questions (e.g. tobacco,
diabetes) and their lipid profile results will be used to calculate the patient's Framingham
risk score, which estimates the 10-year CV risk of the patient.
Inclusion Criteria: Only those patients that 1) are 20 years of age or older 2) have RA
fulfilling the American College of Rheumatology criteria, 3) have zero or more swollen
joints, 4) are receiving stable pharmacotherapy (defined as greater than 3 months of
unchanged antirheumatic drugs and greater than 1 month of unchanged nonsteroidal
anti-inflammatory drugs), 5) have moderate risk of CVD as identified by the Framingham risk
score, 6) are able to walk on treadmill or cycle on a stationary bike for 15 minutes and 7)
are able to attend the Community Cardiovascular Hearts in Motion program (held in the Halifax
Regional Municipality) will be asked to participate in the study. Any patients that meet the
inclusion criteria, but are 1) known to have coronary, cerebral or peripheral artery disease,
2) taking statins, or 3) have one or more arthroplasties of weight bearing joints, will not
be eligible to participate in the study.
Sample Size: The study will recruit 60 participants, 30 CON and 30 CRH..
Outcome measures: Variables pertaining to RA, CVD and PA will be measured in all subjects
(CON, CRH) at two different time points during the study. Specifically, the subjects will be
assessed at baseline (week-0) and then be reassessed post 12-week intervention (week-13). The
post CR intervention assessment will be conducted 72 hours after the completion of the final
exercise session. The variables that will be measured at week-0 and week-13 are listed in
section B1e and the tools used to assess these outcomes are described below. Of note, the
physicians/nurse conducting the assessments will be blinded in regards to which group the
subject is assigned to.
RA Severity: Severity of RA will be determined using the American College of Rheumatology
(ACR) response score. The ACR is a composite score based on 7 measures: 3 by an assessor
(swollen joint, tender joint count and physician global status), 3 by the patient (function,
pain and global status) and one acute phase measure (CRP). The ACR examination will be
conducted by a rheumatologist (VB, Coinvestigator).
Aerobic Fitness: The subject's aerobic fitness will be determined based on the results from a
stress test. All stress tests will be conducted by a cardiac research nurse. In brief,
subjects will perform a graded exercise test (Bruce treadmill protocol) where speed and
inclination of the treadmill increase every 3 minutes. The subject will be asked to exercise
to volitional fatigue. Cardiac function will be monitored with a 12 lead ECG. The ECG data
also will be used to determine if there is any evidence of cardiac disease (e.g. arrhythmia).
Predictive equations developed for men and women will be used to calculate the subject's peak
oxygen uptake. This value will represent the subject's aerobic fitness.
Physical Activity: The subject's current level of PA will be measured using the long form of
the International Physical Activity Questionnaire. This questionnaire is suitable for use
with clinical populations and has been used previously to quantify physical activity levels
in RA patients.
Functional Ability: Functional status will be assessed using the short form of the Health
Assessment questionnaire (HAQ). This is a self report questionnaire that is comprised of the
HAQ disability index, HAQ patient global health status and the pain visual analog scale.
Blood Analysis: Blood samples will be drawn by either the research nurse or a physician.
Samples will be processed at the local hospital to determine the subject's lipid profile,
fasting glucose and CRP levels. Serum also will be extracted from the blood samples. Markers
of systemic inflammation (cytokines) will be quantified in the serum samples. Specifically,
tests will quantify levels of the proinflammatory cytokines IL-1α, IL-1β, IL-6, IL-17 and
TNFα as well as the anti-inflammatory cytokines IL-4 and IL-10. Analysis will be performed at
Dalhousie University (SG, PI) using a BioRad Bioplex Suspension Array System. All serum
samples will be stored at -20°C until they are required for analysis.
Exercise Intervention:
Subjects will be randomly assigned to either the CON or CRH group. Subjects assigned to the
CON will receive treatment for their RA that is considered standard care (e.g.
pharmacotherapy), but will not be enrolled in the CR program. Subjects in the CON group will
be asked to maintain their current level of PA during the course of the 12-week study. CON
subjects will be given a log book to record their daily activity as well as report any
significant changes in their PA level that occur during the study. Subjects assigned to the
exercise group (CRH) will receive standard care for RA plus be enrolled in a CR program
(Community Cardiovascular Hearts Motion Program, Halifax Regional Municipality, NS). The CR
program is 12-weeks in duration and will be supervised by a nurse, a physiotherapist and a
research assistant. The CR program is composed of one 60 minute education session per week
and two 60 minute exercise sessions. The education sessions will be conducted by a
multidisciplinary team of health professionals (nurse, physiotherapist and dietician). Topics
covered include heart healthy eating, setting health-related goal, exercise, nutrition,
healthy weight, smoking cessation and stress/coping. Some education sessions will be modified
to better suit RA subjects (e.g. CVD medication session). The exercise sessions are based on
standard of care for CVD patients. Exercise sessions will begin with a group a warm-up
activity, followed by 45 minutes of aerobic activity and ending with a cool down. Aerobic
activity will consist of walking/running on a treadmill, stepping exercise and/or cycling on
a cycle ergometer. The subject will be encouraged to rotate through the various exercise
machines (e.g. 15 minutes treadmill, 15 minutes cycle, 15 minutes stepper). All aerobic
exercise will be performed at high intensity, which for the present study is defined as
exercise that elicits a HR between 60-80% of heart rate reserve (HRR). Subjects will keep a
log book for the duration of the program that details their exercise sessions. Subjects will
record resting heart rate, type of exercise performed, duration of the exercise and HR during
the exercise sessions. The subject also may add any relevant notes. All exercise sessions
will be closely monitored by a nurse, physiotherapist and a research assistant. Prior to the
initial CR exercise session target heart rates will be calculated for each subject based on
the maximum HR achieved during their stress test. Subjects will be taught how to palpate
radial and/or carotid pulse during the first week of the CR program. This will enable the
subject to monitor and maintain their HR within the target HR zone while performing their
aerobic exercise.