Multiple sclerosis (MS) is a highly prevalent disease of the central nervous system and is a leading cause of non-traumatic disability among young adults in the United States (Olek, 2021; Ligouri et al., 2000). Early initiation of disease-modifying therapies (DMTs) is the first-line of treatment (Hartung et al., 2021), yet people with MS still experience symptom worsening and reduced health-related quality of life (HRQOL) (Ontaneda et al., 2024). This highlights the need for complementary rehabilitation strategies and lifestyle interventions, particularly in the early stages of MS (Kalb et al., 2020).

Physical activity (PA) is a potent lifestyle behavior for managing MS symptoms and comorbid conditions, slowing relapse rate and disability progression, and improving HRQOL in MS (Suh et al., 2015; Motl et al., 2011; Pilutti et al., 2014). Nevertheless, PA levels remain low among those with MS, including people newly diagnosed with MS (PNDwMS) and it is seldom promoted early after MS diagnosis (Jeng et al., 2024; Gervasoni et al., 2022; Huynh et al., 2022). Of note, approximately 40 % reported stopping PA after an MS diagnosis (Frau et al., 2015). The early stages of MS may represent an ideal window for promoting PA as it could offer life-long benefits, yet MS research has not systematically focused on developing interventions and supporting PA adoption in PNDwMS (Huynh et al., 2022; Riemenschneider et al., 2018).

We recently developed a theory-based PA behavioral intervention grounded in the Capability-Opportunity-Motivation-Behavior (COM-B) model and the Behavior Change Wheel (BCW) for PNDwMS (Pekmezi and Motl, 2022; Glanz and Bishop, 2010; Michie et al., 2011). Our phase-1 clinical trial indicated that the PA intervention was feasible and yielded improvements in device-measured and self-reported PA and HRQOL in PNDwMS (Huynh et al., 2024). However, our Phase-1 trial involved a pre-post design without a control condition.

To that end, we proposed and conducted a Phase-2 randomized controlled trial (RCT) that examined the efficacy of a 16-week remotely delivered behavioral intervention for promoting lifestyle PA in PNDwMS (i.e, disease duration ≤ 2 years) (Huynh and Motl, 2025). The RCT examined changes in primary (i.e., device-measured and self-reported PA) and secondary (i.e., fatigue, depression, anxiety, and HRQOL) outcomes compared with waitlist control (WLC) condition. We hypothesize that the 16-week PA intervention would yield significantly greater improvements in the primary and secondary outcomes than the WLC condition.