Short-term Exercise Interventions Do Not Produce Significant Motor Benefits in Huntington’s Patients, Meta-analysis Reports

A combined data analysis of five studies examining the effects of short-term exercise interventions in Huntington’s disease (HD) did not find any evidence of statistically significant motor improvements.

The investigators suggest more supervised trials of longer duration and with common outcomes are necessary in order to evaluate the effects of exercise in this patient population.

Their study, “Exercise Interventions in Huntington’s disease: An Individual Patient Data Meta-Analysis,” was published in the journal Movement Disorders Clinical Practice.

People with Huntington’s disease can lose some independence in daily activities, even during the early stages of the disease. While current therapeutic interventions focus on symptom management, so far none can effectively produce a disease-modifying effect.

“The evaluation of non-pharmacological interventions, such as exercise and physical activity, as both stand-alone and adjunctive therapies, has therefore never been more relevant,” the researchers wrote.

Some evidence supports the benefits of exercise and physical activity in Huntington’s disease, namely in terms of motor function and in a range of physical and social parameters. However, these have been identified through patient-reported outcomes, and large-sample randomized controlled trials have not been available.

The study authors had previously conducted five randomized controlled trials focused on aerobic conditioning, strength training, flexibility and balance exercises, task-specific training, and promotion of physical activity. These trials — Move to Exercise (ISRCTN 59910670), COMMET-HD (ISRCTN11392629), ENGAGE HD (ISRCTN 65378754), TRAIN HD (a home-based exercise program), and ExeRT-HD (ISCTRN94284668) — showed that exercise interventions were feasible and acceptable in people with early- to mid-stage Huntington’s disease.

“Although these studies have evaluated relatively short-term (8–16 weeks) interventions, individually they have provided some indication that changes in motor function, mobility, endurance, fitness, and quality of life can be achieved through regular exercise and physical activity,” the researchers wrote.

However, none of these individual studies had the statistical power to demonstrate that these short-term interventions were significantly beneficial.

To attain statistical significance and demonstrate that an intervention is beneficial, large-scale long-term clinical trials are needed. However, this goal is difficult to achieve in Huntington’s disease, given that it’s a rare condition and the fact that many specialized clinics are geographically distant.

“This latter issue is further compounded in exercise trials, where in-person visits are essential to ensure intervention fidelity,” the researchers wrote.

An alternative is to increase the overall statistical power by combining individual patient data from several small, previously published clinical trials. This is called a meta-analysis.

Therefore, the researchers conducted an individual patient data meta-analysis across the five previously conducted feasibility trials of exercise intervention in patients with Huntington’s disease.

The meta-analysis involved 121 participants from the five studies who had Huntington’s disease confirmed by genetic testing and neurological examination. Patients were older than 18 years (average age of 53.2 years) and about half (50.4%) were male.

Patients were on a stable medication regimen for four weeks before starting the trials and were able to maintain that regimen during the trials.

Exercise involved a combination of supervised and self-directed physical activity in sessions over eight to 16 weeks, with varied emphasis on aerobic, strength, endurance, flexibility, and task training.

The primary outcome was improvement in the Unified Huntington’s Disease Rating Scale’s modified Motor Score, a rating system to quantify disease severity. A higher score indicates a worse outcome.

Secondary outcome tests measured cognitive impairment, balance, leg strength and endurance, mobility, gait speed, physical performance, anxiety and depression, health status, and quality of life.

The meta-analysis showed that these short-duration exercise interventions produced no significant effects on the modified motor score. Regarding secondary outcomes, only those measured in at least three studies were included in the meta-analysis. However, none of the outcomes demonstrated “evidence of effect.”

Heterogeneity between studies, including the components, duration, intensity, and frequency of exercise, made it difficult to reach definitive conclusions, the researchers noted.

“Future interventions must be delivered for longer durations and should consider frequency and intensity of exercise. Furthermore, supervision and support to exercise appear to be critical factors in facilitating adherence and optimizing outcome,” they said.