Department of Medicine, The University of British Columbia, Vancouver, British Columbia, Canada
Post-COVID-19 Interdisciplinary Clinical Care Network, Vancouver, British Columbia, Canada.
BMJ Open. 2024 May 13;14(5):e085272. doi: 10.1136/bmjopen-2024-085272.
A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required.
A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19-69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire.
The trial has been authorised by Health Canada and approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences.
NCT05430152.
相当一部分患有新冠后疾病（PCC，也称为长新冠）的患者会出现持续性、致残性疲劳，类似于慢性疲劳综合征/肌痛性脑脊髓炎（ME/CFS）和病毒性疲劳综合征。目前，对于这种亚型的 PCC 患者，还没有明确的药物治疗方法，这种疾病可以被称为新冠后疲劳综合征（PCFS）。小剂量阿片类拮抗剂纳曲酮（即低剂量纳曲酮（LDN））已成为治疗 PCC 疲劳和其他症状的一种非标签治疗方法。然而，只有小规模的、非对照研究评估了 LDN 在 PCC 中的作用，因此迫切需要进行随机试验。
一项前瞻性、随机、双盲、平行臂、安慰剂对照的 II 期试验将评估 LDN 改善 PCFS 疲劳的疗效。该试验将分散进行，并向整个加拿大不列颠哥伦比亚省（BC）的合格个人开放。参与者将通过全省性的新冠后多学科临床护理网络（PC-ICCN）和研究志愿者平台（REACH BC）招募。合格的参与者年龄在 19-69 岁之间，在至少 3 个月前被确诊或医生怀疑患有 SARS-CoV-2 感染，并符合改编自医学研究所 ME/CFS 标准的 PCFS 临床标准。正在服用阿片类药物、在新冠之前患有 ME/CFS 或有严重肝脏疾病史的患者将被排除在外。参与者将被随机分配到 LDN 干预组（n=80）或安慰剂组（n=80）。每组参与者将被开相同的胶囊，起始剂量为每天 1mg，并按照预先规定的方案逐步增加剂量至每天 4.5mg 或最大耐受剂量。试验将持续 16 周，在基线、6、12 和 16 周进行评估。主要终点是 16 周时疲劳严重程度，用疲劳严重程度量表评估。次要终点包括疼痛视觉模拟量表评分、总体症状严重程度，用患者表型问卷短表测量、7 天步数和健康相关生活质量，用 EuroQol 5 维度问卷测量。
该试验已获得加拿大卫生部的授权，并获得不列颠哥伦比亚大学/不列颠哥伦比亚省儿童医院和妇女健康中心伦理委员会的批准。试验完成后，将通过现有的 PCC 和 ME/CFS 网络中的参与活动向患者、护理人员和临床医生传播研究结果。结果将发表在学术期刊上，并在会议上展示。
NCT05430152。
