There were no differences between the val/val and val/met genotypes for all outcome measures except the 6MWT in the on phase (P = 0.06) (see Supplement D, Supplemental Digital 5, available at: http://links.lww.com/JNPT/A248). There were no differences in blood concentrations (BDNF, SOD, and cytokines) and performance-based assessments based on BDNF genotype (see Supplement D, Supplemental Digital Content 5, available at: http://links.lww.com/JNPT/A248).
Results of this pilot study suggest that a high-intensity multimodal exercise program in persons with PD is feasible and safe, which is consistent with a meta-analysis of studies related to intensive exercise in persons with PD.96 Despite similar levels of participation, HIBC participants were more likely to attain CDC aerobic and strength guidelines than UC participants. Participants in both arms had a positive experience and felt their programs were safe and enjoyable. Interestingly, both groups perceived that their exercise program was intense with no difference between them. This suggests that relying solely on self-report of intensity may not give an accurate representation of exercise capacity since the intensities were clearly different.
Our data suggest that intensity may matter as the participants in the HIBC group experienced improvements across more domains than the UC participants. Of the 31 outcome measures, HIBC participants improved in 7 whereas UC participants improved in 3 (see Table 4 and Supplement B, Supplemental Digital Content 3, available at: http://links.lww.com/JNPT/A246). The effect size of many of the nonsignificant outcomes indicates that they were underpowered especially in the HIBC group where effect sizes were quite large. HIBC effect sizes were in the positive direction (improvement) in 26 of the 31 outcomes (4 negative direction [worsened], 1 unchanged) whereas in UC there were 20 positives and 11 negatives. There were no statistically significant deteriorations in any outcome for either group. While results from the outcome measures do not give unequivocal evidence that the HIBC was better, they do provide a signal of efficacy that they may be. These findings are consistent with meta-analyses on high-intensity exercise for PD,96 physical therapy for PD,27 and balance training in persons with PD.33 However, it should be noted that few participants in both arms improved beyond the minimal detectable change for outcome measures with PD-derived minimal detectable change values (see Supplement E, Supplemental Digital Content 6, available at: http://links.lww.com/JNPT/A249). In light of this, these results should be interpreted with some caution.
Despite the positive experience from participants in both arms, there was little exercise engagement in the 6-month posttrial period. Imparting a behavioral change regarding participation in regular exercise was a secondary focus, and the lack of participation after the trial is concerning. One inclusion criterion was that participants were “nonexercisers”: this may have created a selection bias in our trial. Because participants were nonexercisers, they may have had a low expectation from exercise, which has been reported as the strongest barrier to engaging in exercise among those with PD.97
Strength improvements were observed only for UC. The resistance training was more intensive in the HIBC, so this lack of improvement is perplexing. However, the only strength measure was the STS test and, in retrospect, it may not have been appropriate for PD because it is a timed-task. Since PD is impacted by bradykinesia, this may have introduced unwanted variance into the assessment. We recommend that future studies use a nontimed strength test. Also, from a design perspective and to avoid task-specific improvements, using a strength test that was utilized as an exercise in only one treatment arm (UC) is also confounding.
Due to the sample size, the feasibility and safety comparisons should be interpreted with caution. However, one should bear in mind that the exposure between the 2 groups was different (HIBC: 90 minutes per session; UC: 60 minutes per session). Excluding regular exercisers was designed to prevent a ceiling effect but made enrollment difficult because many PD volunteers tend to be active. Another weakness was that 8 weeks may not have been long enough to drive meaningful changes in the outcomes and promote behavioral change. It should also be noted that the CDC goal for 150 minutes was not met for most participants with just the HIBC or UC programs at the gym; it required the addition of the home exercises. In addition, it should be noted that the in-gym exercises were monitored using heart rate monitors whereas the home exercise was self-reported.
The high-intensity multimodal exercise boot camp protocol used in this trial is feasible for people with PD with good compliance and better attainment of CDC aerobic and strength guidelines than UC. Compared with UC, there were no differences in the rate of adverse events. Our results suggest that the intensity may matter as those in the high-intensity arm had more improvements across more domains than UC. Lastly, our results provide preliminary evidence of a possible link between improvement in outcomes and potentially neuroprotective anti-inflammatory conditions.
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