Prospective, Randomized, Double-blind, Placebo-controlled Phase 2a Trial of Low-dose Aripiprazole in Patients With Neuropsychiatric Impairment in Post-acute Infectious Syndrome (PAIS) Including Post-COVID-19 Condition (PCC)
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 138
- 试验地点
- 1
- 主要终点
- Intra-patient change in the Chalder Fatigue Scale (CFQ) by ≥ 3 points from baseline to week 9 in patients with PAIS.
研究概览
简要总结
Post-acute infectious syndrome (PAIS), including post-COVID-19 condition (PCC or Long COVID), can develop after an infection and may cause persistent symptoms such as fatigue, problems with memory and concentration ("brain fog"), mood changes, and reduced quality of life. In some people, these symptoms continue for months or longer and can substantially affect daily activities. Currently, there are no approved treatments that specifically target these symptoms.
Aripiprazole is a medicine that is approved to treat certain psychiatric disorders. At low doses, it may affect brain signaling and immune processes that are thought to contribute to symptoms experienced by people with PAIS. Small observational studies have suggested that low-dose aripiprazole may improve symptoms such as fatigue and cognitive impairment in people with related conditions, but its effectiveness and safety have not yet been confirmed in a randomized controlled trial.
The purpose of this study is to evaluate whether low-dose aripiprazole is safe and more effective than placebo in improving fatigue and other neuropsychiatric symptoms in adults with PAIS.
This is a phase 2b, randomized, double-blind, placebo-controlled crossover trial. Approximately 138 participants with PAIS will be enrolled. Participants will be randomly assigned to one of two treatment sequences. One group will receive low-dose aripiprazole for 8 weeks followed by placebo for 8 weeks. The other group will receive placebo first, followed by low-dose aripiprazole. The two treatment periods will be separated by a 2-week washout period. Neither the participants nor the study team will know which treatment is being given during each treatment period.
The primary objective is to determine whether low-dose aripiprazole improves fatigue after the first 8-week treatment period compared with placebo. Fatigue will be assessed using the Chalder Fatigue Questionnaire. Secondary objectives include evaluating the effects of treatment on physical functioning, quality of life, memory and cognitive performance, mood, post-exertional malaise, illness-related anxiety and distress, and fatigue in participants who meet diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Safety will be assessed throughout the study by monitoring adverse events.
The results of this study may help determine whether low-dose aripiprazole is a safe and effective treatment option for people with PAIS
详细描述
Background: Post-acute infectious syndrome (PAIS) describes persistent health problems that develop after an acute infection and continue for at least three months. The condition includes post-COVID-19 condition (PCC or Long COVID) but may also occur after other viral or bacterial infections. Common symptoms include severe fatigue, problems with memory and concentration ("brain fog"), post-exertional malaise (worsening of symptoms after physical or mental activity), sleep disturbances, mood changes, and reduced physical functioning. These symptoms can substantially impair daily activities, work, education, and quality of life. Although the number of affected individuals has increased considerably in recent years, there are currently no approved pharmacological treatments specifically targeting the neuropsychiatric symptoms of PAIS. Management is largely limited to supportive care and symptom-based treatment. There is therefore a substantial need for safe and effective therapies.
Study Rationale: Aripiprazole is an atypical antipsychotic that has been approved for many years to treat psychiatric disorders such as schizophrenia and bipolar disorder. At considerably lower doses than those used in psychiatry, aripiprazole has pharmacological effects that may influence dopamine signaling, neuroinflammation, and immune regulation, mechanisms that have been proposed to contribute to the development and persistence of symptoms in PAIS. Preliminary observational studies have suggested that low-dose aripiprazole may improve fatigue, cognitive symptoms, and overall functioning in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a condition that shares many clinical features with PAIS. However, these findings have not yet been confirmed in randomized controlled clinical trials. The PAIS-AriSE study has been designed to evaluate the efficacy and safety of low-dose aripiprazole using a rigorous randomized, double-blind, placebo-controlled study design.
Study Objectives: The primary objective is to determine whether treatment with low-dose aripiprazole results in greater improvement in fatigue than placebo after the first 8-week treatment period.
Secondary objectives include evaluating the effects of treatment on:
- fatigue in participants fulfilling diagnostic criteria for ME/CFS;
- fatigue severity and physical functioning;
- health-related quality of life;
- memory performance and other cognitive functions;
- mood;
- post-exertional malaise;
- illness-related anxiety and distress; and
- the safety and tolerability of low-dose aripiprazole.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, 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
- •Male, female or diverse adult who is 18 years or older at the time of informed consent
- •Potential participant is willing, understanding and able to provide informed consent
- •Signed informed consent prior to initiation of any trial-related measure
- •History of confirmed or suspected (PCR or serology or rapid antigen detection, certificate of attending physician, sick note) infectious disease
- •Ongoing symptoms of PAIS/PCC for ≥ 3 months
- •Self-reported neuropsychiatric symptoms at screening
- •For women of childbearing potential (WOCBP):
- •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 randomization, and practicing a highly effective birth control method (failure rate of less than 1%)
排除标准
- •Prior chronic neuroimmunological or neurodegenerative disease
- •Severe psychiatric disease (psychosis, bipolar disorder, severe major depression with inpatient treatment) within the last 10 years
- •Current malignant disease (including space-occupying brain tumors)
- •Concomitant antipsychotic medication
- •Patient is allergic or has contraindication to Aripiprazole or lactulose and cellulose
- •Patient is pregnant or breastfeeding
- •WOCBP who are unwilling to use an effective method of contraception as defined in inclusion criterion above
- •Bell disability scale < 30
- •Participation in another interventional clinical trial within the last 3 months or within five half-lives of the investigational product (whichever is longer)
- •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 potential participant to attend the planned study visits
- •Other conditions that are likely to affect the safety of the study treatment (e.g. severely impaired immune status)
结局指标
主要结局
Intra-patient change in the Chalder Fatigue Scale (CFQ) by ≥ 3 points from baseline to week 9 in patients with PAIS.
时间窗: 9 weeks after first IMP intake
The CFQ assesses the extent and severity of fatigue and has been used in multiple randomized controlled trials of behavioral interventions in patients with ME/CFS. Each of the 11 items is rated on a 4-point scale, resulting in a total score ranging from 0 (no symptoms) to 33 (maximum symptom severity). In this trial, intra-patient change in CFQ by ≥3 points from baseline to week 9 will be interpreted as meaningful improvement.
次要结局
- Intra-patient change in CFQ by ≥3 points from baseline to week 9 in the subgroup fulfilling ME/CFS criteria.(9 weeks after first IMP intake)
- Intra-patient change in CFQ from baseline to week 19 and from week 9 to week 19.(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Fatigue Severity Score (FSS) from baseline to week 9 and to week 19 and from week 9 to week 19.(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Bell Disability Scale from baseline to week 9 and to week 19 and from week 9 to week 19(9 and 19 weeks after first IMP intake)
- Intra-patient change in the PROMIS-29 questionnaire from baseline to week 9 and to week 19 and from week 9 to week 19.(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Short Form 36 Health Survey - Physical Functioning (SF-36 PF) from baseline to week 9 and to week 19 and from week 9 to week 19(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Multifactorial Memory Questionnaire (MMQ) subscale memory satisfaction from baseline to week 9 and to week 19 and from week 9 to week 19(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Becks Depression Inventory (BDI-II) from baseline to week 9 and to week 19 and from week 9 to week 19(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Post Exertional Malaise (PEM) questionnaire from baseline to week 9 and to week 19 and from week 9 to week 19(9 and 19 weeks after first IMP intake)
- Intra-patient change in the Somatic Symptom Disorder-B Criteria Scale (SSD-12) from baseline to week 9 and to week 19 and from week 9 to week 19(9 and 19 weeks after first IMP intake)
- Difference in the occurrence of Adverse Events (AE) and Serious Adverse Events (SAE) between Aripiprazole and Placebo (IMP safety).(9 and 19 weeks after first IMP intake)
研究者
Christiana Franke
Senior physician
Charite University, Berlin, Germany