High-intensity exercise may be safe and effective in slowing the progression of motor symptoms in patients with newly diagnosed Parkinson’s disease (PD) and who haven’t yet started medication, new research suggests.
The phase 2 randomized, multisite Study in Parkinson Disease of Exercise (SPARX) included 128 patients with de novo PD. Results showed that those who participated in high-intensity treadmill exercise (defined as exercise at 80% to 85% of maximum heart rate) up to 4 days a week had significantly less change from baseline to 6 months on the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score compared with those receiving usual care — the primary clinical outcome.
Although the patients who were assigned to moderate-intensity treadmill exercise (defined as 60% to 65% maximum heart rate) did not have 6-month scores that differed significantly from those in the usual-care group, principal investigator, Margaret Schenkman, PhD, professor in the School of Medicine and associate dean for physical therapy education at the University of Colorado, Aurora, told Medscape Medical News that doesn’t mean only high-intensity exercise is beneficial.
“What we know from a whole huge body of work is that doing anything is better than doing nothing. If I were recommending to a person with Parkinson’s what to do, I’d recommend they try high-intensity exercise three times a week; but I wouldn’t say, ‘Don’t exercise at moderate intensity.’ Something is always better than nothing,” she said.
“The higher intensity is probably better, but it’s important to keep moving and to keep exercising at whatever intensity.”
Dr Schenkman noted that SPARX was designed as a futility trial to see whether the effect of endurance exercise on PD severity was worth continued assessment in a larger phase 3 study. The researchers are now in the beginning stages of planning for the funding of such a trial.
The study was published online December 11 in JAMA Neurology.
First Study of Its Kind
Although many studies over the years have suggested that exercise is beneficial for patients with PD, showing improved gait and muscle strength, improved balance, and improved quality-of-life scores, as well as a reduction in falls, Dr Schenkman said this is the first PD study to look at doses of exercise vs “not doing anything or just doing what one usually does” in modifying disease severity. And it’s the first to assess this in patients with a new PD diagnosis.
“One of the pressing questions has been: What dose of exercise do people with Parkinson’s really need? We have very little information about how intense, how long, how much. It’s been hard to answer what the right prescription is,” she said.
SPARX trial participants aged 40 to 80 years were enrolled between May 2012 and November 2015 at sites in Denver, Colorado; Pittsburgh, Pennsylvania; or Chicago, Illinois. Although 384 patients were initially screened by phone, 154 were found to be eligible. As a result, 128 were included in the three-group randomization (mean age, 64 years; 57% men).
All patients had received a diagnosis of PD at Hoehn and Yahr stage 1 or 2 less than 5 years previously and were “not expected to need dopaminergic medication within 6 months.” This criterion was used in order to remove it as a potential confounder, write the investigators.
The patients were assigned to one of the following regimens for 6 months: high-intensity treadmill exercise 4 days per week (n = 43); moderate-intensity treadmill exercise 4 days per week (n = 45); or usual care (n = 40), which meant that participants were told to engage in their usual exercise habits.
Each exercise group started 5 to 10 minutes of warm-up and cool-down wrapped around 30 minutes of treadmill exercise at the targeted heart rate. Exercise intensity was measured using a heart rate monitor, which had downloadable data.
In addition to the clinical outcome measure of UPDRS motor score at 6 months, trial feasibility outcomes included safety and adherence to targeted exercise intensity at least 3 days per week. Exercise frequency determined adherence rates.
“Nonfutility Threshold” Reached
The mean change in UPDRS motor score was 0.3 (95% confidence interval [CI], –1.7 to 2.3) for the high-intensity group vs 3.2 (95% CI, 1.4 – 5.1) for the usual-care group (P = .03).
The 6-month score for the moderate-intensity group was 2.0 (95% CI, 0.38 – 3.7), which did not differ significantly from the score in the usual-care group.
“The high-intensity group, but not the moderate-intensity group, reached the predefined nonfutility threshold compared with the control group,” write the researchers.
Both exercise intensity standards were safe and feasible. The high-intensity group had a mean maximum heart rate of 80.2% (95% CI, 78.8% – 81.7%) compared with 65.9% (95% CI, 64.2% – 67.7%) in the moderate-intensity group.
The mean exercise frequency was 2.8 and 3.2 days per week, respectively, “with a slight negative trend over time,” the investigators report.
“Anticipated adverse musculoskeletal events were not severe,” they add. There were 15 musculoskeletal and connective-tissue events in the high-intensity group, 6 in the moderate-intensity group, and 2 in the usual care group. The numbers of these events that were classified as greater than mild were 10, 4, and 2, respectively.
Thirteen adverse events of any type related to exercise occurred in the high-intensity group and 8 in the low-intensity group. Only 9 and 4 of these events, respectively, were greater than mild in severity.
In addition, one each of the serious advent events gastrointestinal tract disorders and renal and urinary tract disorders developed in the moderate-intensity group, but neither was deemed to be exercise related.
More Research Needed
Finally, secondary outcomes included UPDRS total and other subscores, the Movement Disorders Society UPDRS (MDS-UPDRS) subscores, maximal aerobic power (mL of oxygen consumed per kg of body weight per minute; VO2max), and total daily step count by accelerometry.
The only significant between-group differences were 6-month change on the MDS-UPDRS motor subscore, which was 4.0 less for patients undergoing high-intensity exercise vs usual care (P = .03), and improved VO2max (P < .001).
Study limitations noted by the investigators include that only treadmill training was measured and that other types of endurance exercise should be assessed in future research.
In addition, “outcomes such as gait speed, gait endurance, and movement economy were not measured,” write the researchers, adding that factors such as cognition and sleep were also not compared between the groups.
“Investigations are needed to determine the combination of interventions that have the greatest effect on motor and other symptoms in patients with de novo Parkinson disease,” they write. While a larger efficacy trial is now warranted, in the meantime, “clinicians may safely prescribe exercise at this [high] intensity level for this population.”
Dr Schenkman added, though, that a clinician should discuss what’s appropriate for an individual patient. “We want people to be safe. So if you have a lot of health conditions that make high-intensity exercise not good for you, by all means do something a little less intense.”
Overall, “the take-away message is that this type of exercise is important; it’s safe; people can do it; and, to the extent it’s possible, it should be at high enough intensity to reach 80% to 85% max heart rate and done on a regular basis,” she said.
“Adds to Growing Evidence”
Asked for comment, Ray Dorsey, MD, professor of neurology and director of the Center for Health + Technology at the University of Rochester Medical Center, New York, told Medscape Medical News that this was a large and rigorous study “that adds to the growing body of evidence” showing that exercise is beneficial for patients with PD.
However, “I’m not convinced that there’s no benefit for moderate-intensity exercise. I think there was just stronger evidence that the higher-intensity was more beneficial in this study,” said Dr Dorsey, who previously directed the Movement Disorders Division at Johns Hopkins University School of Medicine, Baltimore, Maryland.
He noted that the main outcome measure was a physician-administered rating scale, which has a high degree of inter-rater variability. Also, he pointed out that participants were observed for 6 months, which is a short period for seeing significant disease progression, “especially because all of these patients had relatively mild Parkinson’s disease.”
“So their ability to see a difference in a group of people with mild disease using a subjective, rater-dependent outcome measure…is limited,” said Dr Dorsey. “It’s not a great assay for measuring the effects of an intervention, generally speaking. It’s just not a very sensitive assay.”
In the investigators’ upcoming phase 3 study, he noted he would like to see patients’ overall activity measured, not just that done in the clinic. “And I’d like to see if people’s mobility increases the more they exercise and are more active in the rest of their lives than a group who is more sedentary.”
Still, “I advise almost all my patients to exercise. That’s usually my number 1 recommendation,” said Dr Dorsey. “There’s an increasing amount of evidence that exercise is beneficial for Parkinson’s disease and even other neurodegenerative conditions.”
The study was supported by grants from the National Institute of Neurologic Disorders and Stroke, the University of Pittsburgh Clinical and Translational Science Institute, the University of Colorado Clinical and Translational Science Award program, the Nutrition and Obesity Research Center, and the National Institutes of Health. It also received support from the Parkinson’s Disease Foundation. Dr Schenkman and the other study authors have disclosed no relevant financial relationships.
JAMA Neurol. Published online December 11, 2017. Abstract