Effectiveness of the adapted Unified Protocol (UP-MSo) in relapsing–remitting multiple sclerosis with overweight/obesity: A pre-registered randomized controlled trial on emotion regulation, eating behavior, and neurological outcomes.

Background: Relapsing–remitting multiple sclerosis (RRMS) is frequently associated with anxiety, depression, and emotion regulation difficulties, which may foster maladaptive coping strategies such as emotional eating and contribute to comorbid overweight/obesity. Transdiagnostic, emotion-focused interventions may be especially relevant for this population. Objective: To evaluate the effectiveness of an adapted group-based Unified Protocol (UP) on emotion regulation, eating behaviors, and medical outcomes in adults with RRMS and overweight/obesity. Methods: A pre-registered single-blind randomized controlled trial (OSF: https://osf.io/sr4bx) compared a 14-session group-based adapted UP (n = 47) against standard medical care (n = 33). Complete pre–post medical data (body mass index (BMI), weight, Expanded Disability Status Scale (EDSS), Symbol Digit Modalities Test (SDMT), magnetic resonance imaging (MRI) brain metrics, T2 lesions) were available for both arms; complete psychological self-report data were available only for the intervention arm. Medical outcomes were analyzed with two-way mixed ANOVAs (Group × Time); psychological outcomes were analyzed within-arm with linear mixed-effects models. Results: Within the intervention arm, significant pre–post improvements were observed in emotion regulation difficulties, emotional eating, and psychosocial impairment, with longitudinal reductions in anxiety and depressive symptoms. Between-group analyses revealed significant Group × Time interactions for BMI (p=.030, ηp²=.07), weight (p=.024, ηp²=.07), and EDSS (p<.001, ηp²=.31), favoring the intervention. No interactions emerged for SDMT, MRI brain volumes, or T2 lesions. Conclusions: Within the intervention arm, the group-based UP was associated with within-group improvements in emotion regulation and disordered eating, and with between-group anthropometric and EDSS outcomes relative to standard care. Because the psychological outcomes were assessed within the intervention arm only, these within-group changes should not be interpreted as treatment effects relative to standard care. EDSS findings should be interpreted as preliminary, as they were not corroborated by confirmed disability improvement criteria or concurrent MRI changes.