Benefits of High-intensity Endurance Exercise Focus of New Northwestern Study

A Northwestern University-sponsored study will assess whether high-intensity treadmill endurance exercise is superior to its moderate-intensity version at slowing disease progression in adults with early Parkinson’s who have not yet started taking any medications for their disease.

While anti-parkinsonian medication helps alleviate Parkinson’s symptoms, “endurance exercise is the only treatment with evidence for slowing Parkinson’s disease progression,” Daniel Corcos, PhD, the study’s principal investigator, said in a university press release.

“If the trial shows high-intensity exercise delays the rate at which Parkinson’s disease progresses, physicians will have a clear guideline to prescribe exercise as a means to slow progression,” said Corcos, a professor of physical therapy and human movement sciences at the Northwestern University Feinberg School of Medicine.

Regular exercise and being physically active are known to have multiple health benefits, such as increasing muscle strength and flexibility, improving the heart’s ability to pump blood, and improving a person’s mental well-being.

Increasing evidence also points to a link between physical activity and brain health, with regular exercise helping to delay brain aging and neurodegenerative diseases such as Parkinson’s.

Notably, previous work has shown that exercise can lessen both motor and non-motor symptoms of Parkinson’s disease, with results suggesting that patients should exercise at least two-and-a-half hours per week to slow decline and maintain a better quality of life.

However, while both moderate and high-intensity aerobic exercise “provide health benefits, it is unclear which intensity is more effective for people with Parkinson’s disease,” Corcos said.

A previous Phase 2 clinical trial (NCT01506479), in which Corcos also was a principal investigator, provided early evidence that high-intensity treadmill endurance exercise three times a week is more effective at preventing motor function worsening in Parkinson’s patients than a moderate-intensity program. Such exercise was found to be safe for patients.

Involving 128 adults newly diagnosed with Parkinson’s, who had received no previous treatment for the disease, that study showed that participants assigned a six-month, high-intensity exercise program maintained their motor abilities — as assessed with the MDS‐UPDRS-Part III score. Meanwhile, those on the moderate-intensity program saw their scores drop by two points.

For reference, participants not undergoing any of the programs showed a three-point drop in the MDS‐UPDR-Part III motor scores.

The upcoming Phase 3 study, called SPARX3 (NCT04284436), now seeks to confirm the therapeutic benefits of high-intensity treadmill endurance exercise in a larger patient population.

The trial, which has not yet started enrollment, aims to recruit 370 people, ages 40 to 80, who were diagnosed with Parkinson’s in the previous three years but have not yet started anti-parkinsonian medication. It will take place at 27 clinical sites in the U.S. and two in Canada. More information on contacts and locations can be found here.

All sites are members of the Parkinson Study Group, a non-profit network of Parkinson’s centers.

Participants will be randomly assigned to undergo 30 minutes of either high-intensity (80–85% of maximum heart rate) or moderate-intensity (60–65% of maximum heart rate) treadmill endurance training, four times a week, for 1.5 years. Each exercise session will be preceded by five minutes of warm-up and followed by a five-minute cool-down.

The 18 month-exercise programs will be conducted under close supervision by the study teams, after which patients will be followed for another six months to evaluate the sustainability and durability of the programs’ benefits after their completion.

The main goal is to assess whether the high-intensity program works better than the moderate program at delaying motor function worsening, as assessed through changes in the MDS‐UPDRS-Part III score.

Secondary goals include changes in participants’ walking abilities, cardiorespiratory fitness, cognitive function, quality of life, and time to initiation of dopamine-targeted therapy.

Changes in dopaminergic neurons — the nerve cells progressively lost in Parkinson’s — and the blood levels of neuronal survival and inflammation biomarkers also will be evaluated.

In addition, the research team will collect genetic information on the participants and assess whether genetic factors may explain why some of them may respond better than others to the exercise program.

The study will be conducted in collaboration with the University of Pittsburgh, the University of Colorado, the Oregon Health Sciences Center, New York University Langone Health, the University of Florida, and the Parkinson’s Foundation.

It is being supported by grants from the National Institute of Neurological Disorders and Stroke and the National Center for Advancing Translational Sciences — both part of the National Institutes of Health — as well as by Northwestern’s Feinberg School of Medicine.