None listed
Conditions
Brief summary
A post-exertional exacerbation of fatigue and other symptoms is a characteristic feature of chronic fatigue syndrome (CFS) following a relatively small amount of physical or cognitive activity. Although it is well established that graded exercise therapy (GET) is beneficial for the management of CFS, this intervention, which uses cautious, symptom-limited increases in gentle aerobic exercise, has only modest effectiveness. The key limiting factor is the delayed exacerbation of symptoms that follows exercise. This post-exertional exacerbation has been well characterized in exercise challenge studies. Modafinil, a psycho-stimulant drug, has been licensed in Australia and internationally and used clinically for some time. Additionally, it has demonstrated some benefit in reducing fatigue in multiple sclerosis, and daytime sleepiness in Parkinson’s disease. In healthy subjects, the effect of a single dose of modafinil on exercise time has been examined and showed a prolonged time to exhaustion of 22% for high intensity exercise (Jacobs and Bell, 2004). Interestingly, the rate of perceived exertion (RPE) reported by participants was statistically significantly lower in the modafinil exercise trial compared to the placebo exercise trial. Since the symptom of fatigue is the limiting factor in the progression of GET, it is appealing to test the possibility that modafinil may attenuate the exacerbation of fatigue following exercise for patients with CFS. This opens up the possibility of greater progression in GET and, therefore, potentially further increases in physical function. However, before a training study is undertaken a systematic evaluation of the acute response of the post-exertional exacerbation of fatigue and symptoms following modafinil is warranted. It is hypothesized that for modafinil compared to placebo, patients will report a lower RPE during exercise and less post-exertional exacerbation of fatigue. The protocol will involve two sessions of a six-day assessment period, each including a 48 hour pre-exercise baseline assessment and 96 hour post-exercise assessment. Each participant (n=20) will be asked to complete two exercise sessions (one with modafinil and one with placebo) separated by at least two weeks. The order of the treatment trial (placebo or modafinil) will be randomised and counter-balanced as well as double-blinded. The exercise bout will consist of moderate-intensity cycling for generally 20 minutes.
Interventions
A post-exertional exacerbation of fatigue (and other symptoms) is a characteristic feature of chronic fatigue syndrome (CFS) following a relatively small amount of physical or cognitive activity. We aim to explore how this post-exertional exacerbation of fatigue following a continuous exercise bout differs with modafinil treatment. The exercise bout will consist of moderate-intensity cycling for generally 20 minutes and each participants’ reaction to the exercise bout will be recorded by monitor
A post-exertional exacerbation of fatigue (and other symptoms) is a characteristic feature of chronic fatigue syndrome (CFS) following a relatively small amount of physical or cognitive activity. We aim to explore how this post-exertional exacerbation of fatigue following a continuous exercise bout differs with modafinil treatment. The exercise bout will consist of moderate-intensity cycling for generally 20 minutes and each participants’ reaction to the exercise bout will be recorded by monitoring worsened fatigue and accompanying symptoms when undertaken in conjunction with modafinil or placebo. After an overnight fast and abstaining from caffeine 12 hours before each test the participants will report to the laboratory and ingest opaque gelatin capsules containing either placebo or 400mg modafinil. Following the capsule ingestion participants will be given an identical meal (e.g. muffin and orange juice) and two hours following they will complete the exercise test. Assessment of symptoms and function will be conducted via self-report questionnaires conducted twice daily (morning and afternoon) 48 hours prior to exercise and for 96 hours following the exercise. Additionally symptoms and function will be assessed immediately prior to exercise (pre-0), and immediately following exercise (post-0). Actigraphy will be recorded for the 24 hours before and 24 hours following the exercise challenge. Algometry (pressure pain threshold) will be assessed immediately before and immediately after the exercise tests. Each participant will be asked to complete two exercise sessions (one with modafinil and one with placebo) separated by at least two weeks (or until the subject feels their exacerbated symptoms have returned to ‘baseline’). Participants will undertake 20 minutes of moderate intensity stationary-cycling exercise, preceded by a 5-minute warm-up (at low intensity approx. 40 Watts) and followed by a 2-minute cool down period (at low intensity approx. 40 Watts). In the event of recruiting people of lower capacity for whom the 20 minute exercise dose would result in too great an exacerbation in symptoms, a shorter duration of exercise, as low as 10mins, will be applied. This group will also complete an abbreviated warm up e.g. 2.5 - 4 minutes. Workload will be adjusted to require 70% of the individual’s age-predicted heart rate maximum (APHRM) for the high capacity group. Intensity will be determined using a standard equation for predicting maximal heart rate (= 208 – 0.7 x age) (Tanaka, Monahan et al. 2001). Resistance will be incrementally augmented during the first 5 minutes of exercise until the target heart rate is reached. The workload will then remain relatively constant throughout the duration of the bout, with minor adjustments to the applied resistance to continually keep the actual heart rate within 3 beats per minute of the target heart rate. The duration of each exercise bout will vary depending based on each participant being able to regularly undertake 10-20 minutes walking at a gentle pace without producing a post-exertional exacerbation of symptoms (as per inclusion criteria). The total and average work from the first exercise bout will be calculated. The second exercise bout will be conducted will be conducted with the same target heart rate along with information on the anticipated workload. With the goal being to match both total workload and mean heart rate between the exercise bouts. These data will provide preliminary information regarding the possible use of modafinil to augment the existing standard of care for patients with CFS (i.e. cognitive behavioural therapy and graded exercise therapy). Hence, this is a physiological investigation of the response to exercise in conjunction with medication to identify possible avenues for future
Sponsors
University of New South Wales
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
i) meeting international diagnostic criteria for chronic fatigue syndrome (Fukuda, 1994) ii) have their treating exercise physiologist and clinical psychologist resolve that they have a stable pattern of symptom severity, as well as having optimized and stable sleep patterns and well-managed mood disturbance iii) undertaking regular of 10-20 minutes walking at a gentle pace without producing a post-exertional exacerbation of symptoms (that is an hour or more of worsened fatigue and other symptoms).
Exclusion criteria
i) currently use beta-blockers or other agents known to affect heart rate response to exercise; or ii) have any medical (e.g. lower limb injury) condition which may preclude reliable participation in exercise testing iii) currently use central nervous system medications (e.g. Benzodiazepines and other sedative-hyponotics (e.g. stilnox), anti-epileptics, high-dose antidepressants (low-dose allowed), iv) are pregnant or breastfeeding v) have hepatic impairment vi) are hypersensitive to modafinil vii) have a history of left ventricular hypertrophy or ischaemic heart disease, or other clinically significant cardiac disease; viii) uncontrolled anxiety disorder, ix) have previously taken modafinil and experienced an adverse reaction. x) taking anti-hypertensives/beta blockers xi) taking corticosteroids xii) taking major analgesics (e.g. oxycodone)
Outcome results
None listed