Phase 2a, Double-blind, Randomized, Placebo-controlled Trial of Methylprednisolone Versus Placebo in Patients with Cognitive Deficits in Post-COVID-19 Syndrome (PCS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 418
- 试验地点
- 2
- 主要终点
- Improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)
研究概览
简要总结
This clinical trial aims to learn about the therapeutic value of Methylprednisolone, a well-known immunosuppressant, on cognitive deficits in patients with post-COVID-19 syndrome (PCS). The main questions it aims to answer are: 1) Does Methylprednisolone improve memory function in PCS patients compared to placebo? 2) Does Methylprednisolone improve other patient centered outcomes in PCS patients such as fatigue, mood and quality of life compared to placebo? 3)What are the side effects of Methylprednisolone in this patient population, and how common are they? Participants in this study will be patients with PCS and cognitive deficits, who will be asked to participate for 52 weeks. They will be randomly assigned to one of two groups: One group will receive Methylprednisolone once daily for six weeks, with a dosage reduction after week 4. The other group will receive a matching placebo once daily for six weeks, following the same titration regimen to ensure blinding. Participants will attend outpatient follow-up visits in weeks 8 and 20, with a final telephone follow-up after 52 weeks. Clinical examinations and safety monitoring will be conducted during the treatment phase. This study's results may help develop more effective therapies for this condition.
详细描述
Around 10-40% of mild COVID-19 patients experience persisting or new symptoms known as post-COVID-19 syndrome (PCS). Neurological symptoms, particularly cognitive deficits and fatigue, are common in PCS, with a higher prevalence in female patients (Boesl et al., 2021; Ceban et al., 2022). The underlying causes of PCS remain unclear, but some evidence suggests autoimmune mechanisms may play a role. Currently, there are no proven treatments for PCS, leading to a need for effective therapies. This randomized controlled trial (RCT) aims to investigate the impact of methylprednisolone, a generally well-tolerated and affordable drug, on cognitive deficits in PCS patients with suspected autoimmune involvement.
The objective is to demonstrate improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ) in patients with post-COVID-19 syndrome treated with Methylprednisolone compared with placebo. Methylprednisolone is a well-known immunosuppressant used for multiple diseases of (suspected) autoimmune etiology.
This is a two-arm, double-blind, randomized, placebo-controlled trial evaluating the effects of Methylprednisolone versus placebo in patients with post-COVID-19 syndrome (PCS) and cognitive deficits. The study spans 52 weeks, and participants will be stratified based on age, sex, and cognitive screening using the Montreal Cognitive Assessment Scale (MoCA). They will be randomly assigned in a 1:1 ratio to receive either Methylprednisolone (including a tapering phase) or placebo for 6 weeks, followed by an additional 6 weeks of open treatment phase with Methylprednisolone after a 6-weeks treatment pause. During the study, follow-up visits will be conducted as outpatient visits in weeks 8 and 20, with a final telephone follow-up after 52 weeks. The screening and baseline examinations will involve recording of medical history, checking inclusion and exclusion criteria, and conducting clinical examinations. The intervention group will receive approximately 1mg/kg body weight oral Methylprednisolone once daily for 6 weeks, with dosage reduction after week 4. The other group will receive a matching placebo once daily for 6 weeks, following the same titration regimen to maintain blinding. The starting dose for both interventions will be Methylprednisolone at approximately 1 mg/kg body weight or matching placebo once per day. Throughout the treatment phase, all participants will undergo safety and monitoring examinations.
This clinical trial is of significant importance as it has the potential to benefit individuals with post-COVID-19 syndrome (PCS) by exploring the effects of Methylprednisolone on cognitive impairment and fatigue. Additionally, it may provide crucial insights into PCS's pathophysiological processes, leading to the development of more effective therapies and improved patient outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Double-Blind.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of confirmed (PCR or serology) SARS-CoV-2 infection according to WHO criteria
- •Ongoing symptoms of PCS for ≥ 3 months
- •Self-reported cognitive deficits at screening
- •Male or female adult who is 18 years or older at the time of informed consent
- •Subject is willing, understanding and able to provide informed consent
- •Signed informed consent prior to initiation of any trial related measure
- •For female subject or divers subjects:
- •Confirmed post-menopausal state, defined as amenorrhea for at least 12 months, or
- •If being of childbearing potential:
- •Negative highly sensitive urine or serum pregnancy test before inclusion, and
- •Practicing a highly effective birth control method (failure rate of less than 1%)
排除标准
- •Any ongoing central nervous system disease
- •Any major psychiatric disease within the last 10 years
- •Previous medical history of gastric ulcer, osteoporosis and/or previous vertebral fractures, rheumatological disease or metabolic disease including diabetes mellitus
- •Ongoing immunosuppressive therapy
- •Patient is pregnant or breastfeeding at screening
- •MMQ memory satisfaction subdomain >50 points at Screening
- •Current malignant disease (including space-occupying brain tumors)
- •Body weight <45kg
- •Severe lactose intolerance
- •Participation in another clinical interventional trial within the last 3 months or five half- lives of the other trial's IMP, if longer than 6 months previous to informed consent
- •Patient is institutionalized by order of court or public authority
- •Patient who might be dependent on the sponsor, the investigator or the trial site
- •Place of living does not allow the subject to attend the planned study visits
- •Other conditions that are likely to affect to safety of the study treatment (e.g., severely impaired immune status)
研究组 & 干预措施
Methylprednisolone
Tested IMP: Methylprednisolone (film-coated tablet). Authorization status: Not authorized in this targeted therapeutic indication; methylprednisolone is authorized for treatment of multiple autoimmune diseases. The tablets being administered in this trial are an official trade product provided by the marketing authorization holder JenaPharm.
Administration: Tablet containing 16 mg/tablet will be administered orally and according to bodyweight groups. Treatment period comprises 6 weeks of blinded daily IMP (investigational medicinal product) intake (verum or placebo) and 6 weeks of unblinded daily intake of Methylprednisolone. The general IMP titration regimen was investigated and proven to be safe in patients with cerebral vasculitis (Schirmer et al., 2020).
干预措施: Methylprednisolone (Drug)
Placebo
Comparator IMP: Placebo (film-coated tablet). Authorization status: Not authorized. To ensure identical conditions with the verum (Methylprednisolone), we will use placebo tablets of the same color and size in identical tablet packages for both the verum and placebo.
Administration: Tablets (7 mm) will be administered orally and according to bodyweight groups. To achieve consistent conditions with the verum, titration will be conducted in a manner similar to the tested IMP (Methylprednisolone). Treatment period comprises 6 weeks of blinded daily IMP intake (placebo or verum) and 6 weeks of unblinded daily intake of Methylprednisolone.
干预措施: Methylprednisolone (Drug)
结局指标
主要结局
Improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)
时间窗: 8 weeks after first IMP intake
The MMQ is a participant-reported measure of memory satisfaction. It consists of three scales measuring separate aspects of metamemory including memory satisfaction, memory ability, and memory strategy. For memory satisfaction, eighteen items are rated on a 5-point Likert scale based on the test taker's experience over the previous two weeks.The score range is 0 to 72, with higher scores indicating a higher degree of satisfaction. A change of 13 points is commonly rated as clinically significant change. In this study, intra-patient change in MMQ subdomain memory satisfaction by ≥15 points from baseline to week 8 will be interpreted as meaningful improvement.
次要结局
- Difference of occurring AE and SAE comparing Methyprednisolone with placebo (IMP safety).(8 and 20 weeks after first IMP intake)
- Long-term improvement in memory satisfaction as measured by the Multifactorial Memory Questionnaire (MMQ)(20 and 52 weeks after first IMP intake)
- Improvement in quality of life (QoL) as measured by the PROMIS questionnaire(8, 20, and 52 weeks after first IMP intake)
- Improvement in physical and mental fatigue as measured by the Chalder Fatigue Scale(8, 20, and 52 weeks after first IMP intake)
- Improvement in fatigue as measured by the Fatigue Severity Score (FSS)(8, 20, and 52 weeks after first IMP intake)
- Improvement in memory ability and memory strategy as measured by the Multifactorial Memory Questionnaire(8 and 20 weeks after first IMP intake)
- Improvement in neurocognitive functions as measured by the Montreal Cognitive Assessment (MoCA)(8 and 20 weeks after first IMP intake)
- Improvement in neurocognitive functions as measured by the symbol digit modalities test (SDMT)(8 and 20 weeks after first IMP intake)
- Improvement in mood as measured by the Becks Depression Inventory (BDI-II)(8, 20, and 52 weeks after first IMP intake)
研究者
Heinrich J Audebert
Deputy Director of the Department of Neurology with Experimental Neurology at Charite Campus Benjamin Franklin
Charite University, Berlin, Germany