To assess the association between variant repeat (VR) interruptions in patients with myotonic dystrophy type 1 (DM1) and clinical symptoms and outcome measures after cognitive behavioral therapy (CBT) intervention.

Adult patients with DM1 were recruited within the OPTIMISTIC trial (NCT02118779). Disease-related history, current clinical symptoms and comorbidities, functional assessments, and disease- and health-related questionnaires were obtained at baseline and after 5 and 10 months. After genetic analysis, we assessed the association between the presence of VR interruptions and clinical symptoms' long-term outcomes and compared the effects of CBT in patients with and without VR interruptions. Core trial outcome measures analyzed were: 6-minute walking test, DM1-Activ-C, Checklist Individual Strength Fatigue Score, Myotonic Dystrophy Health Index, McGill-Pain questionnaire, and Beck Depression inventory—fast screen. Blood samples for DNA testing were obtained at the baseline visit for determining CTG length and detection of VR interruptions.

VR interruptions were detectable in 21/250 patients (8.4%)—12 were assigned to the standard-of-care group (control group) and 9 to the CBT group. Patients with VR interruptions were significantly older when the first medical problem occurred and had a significantly shorter disease duration at baseline. We found a tendency toward a milder disease severity in patients with VR interruptions, especially in ventilation status, mobility, and cardiac symptoms. Changes in clinical outcome measures after CBT were not associated with the presence of VR interruptions.

The presence of VR interruptions is associated with a later onset of the disease and a milder phenotype. However, based on the OPTIMISTIC trial data, the presence of VR interruptions was not associated with significant changes on outcome measures after CBT intervention.

ClinicalTrials.gov NCT02118779.

评估 1 型强直性肌营养不良 (DM1) 患者的变异重复 (VR) 中断与认知行为疗法 (CBT) 干预后的临床症状和结果测量之间的关联。

患有 DM1 的成年患者在 OPTIMISTIC 试验 (NCT02118779) 中被招募。在基线和 5 个月和 10 个月后获得疾病相关病史、当前临床症状和合并症、功能评估以及疾病和健康相关问卷。经过基因分析，我们评估了 VR 中断的存在与临床症状的长期结果之间的关联，并比较了 CBT 对有和没有 VR 中断的患者的影响。分析的核心试验结果测量是：6 分钟步行测试、DM1-Activ-C、清单个人力量疲劳评分、强直性营养不良健康指数、McGill-Pain 问卷和贝克抑郁量表 - 快速筛选。在基线访问时获得用于 DNA 测试的血样，以确定 CTG 长度和检测 VR 中断。

在 21/250 名患者 (8.4%) 中可检测到 VR 中断——12 名被分配到标准护理组（对照组），9 名被分配到 CBT 组。当第一个医疗问题发生时，VR 中断的患者年龄显着增加，并且基线时的疾病持续时间显着缩短。我们发现 VR 中断患者的疾病严重程度倾向于较轻，尤其是在通气状态、活动能力和心脏症状方面。CBT 后临床结果测量的变化与 VR 中断的存在无关。

VR 中断的存在与疾病的较晚发作和较温和的表型有关。然而，基于 OPTIMISISTIC 试验数据，VR 中断的存在与 CBT 干预后结果测量的显着变化无关。

ClinicalTrials.gov NCT02118779。