Long-term trials of interventions to promote physical activity in people with Huntington’s disease are feasible, with a “nested trial” approach that assigns some patients already participating in an observational study to one group of activities, while others serve as controls, one study reported.
The one-year effort was designed as a nested trial, also called a trial-within-a-cohort study, and its investigators consider this approach the “critical next step in advancing the evidence supporting nonprescription lifestyle interventions.” pharmacological in [Huntington’s] disease management.”
The study, “Physical Activity and Exercise Outcomes in Huntington’s Disease (PACE-HD): Results of a 12-Month Cohort Trial Feasibility Study of a Physical Activity Intervention in People with Huntington’s Disease”, was published in Parkinsonism and related disorders. The work was funded by the Jacques and Gloria Gossweiler Foundation.
Huntington’s often short-run exercise tests
Physical activity plays an important role in health, and some research has suggested that being more physically active may benefit people with Huntington’s. However, existing research in this area has notable limitations, with most studies being small and short-term.
Still, these “short-term (6 to 8 weeks) intervention studies provide preliminary support for the benefits of [physical activity] …in terms of motor function, as well as patient-reported physical and social benefits,” the researchers wrote.
Huntington’s disease is a rare and progressive neurological disorder that poses a number of logistical hurdles when it comes to conducting large, long-term studies with rigorous scientific design. Pragmatic designs such as nested trials, or a trial within a cohort (TWiC), can help overcome these obstacles. TWiC, as noted, basically involves recruiting a large group of patients who are already participating in an observational study, with some randomized to be part of an active intervention while others are not.
“This was particularly relevant given the knowledge that participants may alter their behavior simply by participating in a clinical trial,” the researchers wrote.
An international group of scientists tested whether it would be feasible to conduct a TWiC-based long-term physical activity study for people with Huntington’s disease.
“The primary objective of this study was to assess the feasibility of a TWiC of a physical therapy-led intervention in terms of recruitment, retention, data completeness, adherence, fidelity, and acceptability,” the team wrote.
Nested trial design within the cohort
Patients at six sites participating in the record ENROLL-HD — the world’s largest observational study of Huntington’s disease — and half of the sites entered a randomized, controlled clinical trial of physical activity, while the other half served as an observational control group. All trial participants were instructed to complete monthly exercise/fall diaries and underwent evaluation every half year.
Half of the trial participants were also assigned to a physical therapy intervention with the aim of boosting physical activity, with a total of 18 sessions over the course of a year. The intervention, led by a trained physical therapist, was tailored to the needs of each individual and aimed to develop a routine of moderate to vigorous exercise for 30 minutes three to five times per week.
“This intervention was successfully delivered in three countries with different languages and healthcare settings,” the researchers wrote, noting that the therapist generally reported high fidelity in identifying patient expectations, exercise adaptation, and interactions. positive relationships between the coach and the participant. Slightly less fidelity was noted in communication and in the participation of family members.
From 2018 to 2019, 274 people were evaluated, 204 met the eligibility criteria and 116 were enrolled in the study, although four withdrew or were lost to follow-up before the study began. Ultimately, 59 people were assigned to the control group and 53 to the trial. After one year, 51 (86.4%) control and 45 (84.9%) trial patients remained in the study.
“This met the pre-specified viability progression criteria of less than 30% dropout for the RCT [randomized controlled trial] cluster. … The retention rate at 12 months was excellent, particularly given that the COVID-19 pandemic negatively affected data completion during the last three months,” the researchers wrote.
Among the 26 trial patients randomized to the intervention, all but three attended more than half of the 18 physiotherapy sessions: two patients withdrew and the third “was reported to be experiencing psychosocial problems that affected his ability to participate in the intervention. the researchers said.
Data from standardized assessments performed at study visits were available for most patients, although there were some issues related to COVID-19 at the end of the study. The researchers also noted some incomplete data among the data collected; for example, only about 67% of the expected exercise/crash diaries were completed. Physical activity records with wearable sensors showed the lowest level of integrity.
“Therefore, we can conclude that nesting a trial within a cohort like Enroll-HD is feasible when planning long-term physical activity. [physical activity] evaluation in [Huntington’s]. However, the incompleteness of the data affected the interpretation of some important results. This was particularly evident for research-grade portable monitors,” the scientists wrote.
Trial data generally suggested that people who underwent the intervention had higher rates of self-reported physical activity and performed better on standard measures of exercise capacity such as the six-minute walk test and oxygen utilization during exercise (measures of predicted VO2 max).
“As a feasibility study, this study was not designed to assess efficacy and the results should be interpreted with caution,” the researchers note.
“We have shown that it is possible to perform and evaluate a long-term physical therapist-led intervention” in people with Huntington’s disease, the researchers concluded. “We have further demonstrated the feasibility of a nested trial within the cohort design, which brings with it potential advantages in efficiency and generalizability, providing study teams to carefully consider the complexity and associated challenges.”