Questa pagina è stata tradotta automaticamente e l'accuratezza della traduzione non è garantita. Si prega di fare riferimento al Versione inglese per un testo di partenza.

Post-acute Infectious Syndrome - Aripiprazole Symptom Evaluation (PAIS-AriSE) (PAISE-AriSE)

15 luglio 2026 aggiornato da: Christiana Franke

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)

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

Panoramica dello studio

Stato

Non ancora reclutamento

Condizioni

Intervento / Trattamento

Descrizione dettagliata

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.

Study Design: PAIS-AriSE is a prospective, randomized, double-blind, placebo-controlled, phase 2b crossover trial. Approximately 138 adults with neuropsychiatric symptoms associated with PAIS will be enrolled to ensure that at least 120 participants complete at least one follow-up assessment.

Following screening and baseline assessments, eligible participants will be randomly assigned in a 1:1 ratio to one of two treatment sequences. Randomization will be stratified by age and sex assigned at birth.

Participants assigned to Sequence A will receive oral low-dose aripiprazole for 8 weeks, followed by a 2-week washout period and then 8 weeks of placebo.

Participants assigned to Sequence B will receive placebo for 8 weeks, followed by the same washout period and then 8 weeks of low-dose aripiprazole.

Study medication and placebo capsules will be identical in appearance. Participants, investigators, and study personnel involved in study conduct and outcome assessment will remain unaware of treatment allocation throughout the study.

Study Assessments: Participants will undergo screening and baseline assessments before treatment begins. During the study, fatigue, physical functioning, quality of life, memory, cognitive performance, mood, post-exertional malaise, and illness-related anxiety and distress will be evaluated using validated patient-reported outcome measures and neuropsychological assessments. Follow-up visits will take place after each treatment period.

The primary efficacy endpoint is the change in fatigue after the first treatment period, measured using the Chalder Fatigue Questionnaire (CFQ). Additional validated questionnaires and neuropsychological assessments will be used to evaluate secondary outcomes.

Safety: Safety will be monitored throughout the study by recording adverse events, serious adverse events, and suspected unexpected serious adverse reactions. The safety profile of low-dose aripiprazole in this patient population will be evaluated alongside its potential clinical benefits.

Expected Significance: The PAIS-AriSE trial is designed to provide high-quality evidence on whether low-dose aripiprazole can safely improve fatigue and other neuropsychiatric symptoms in people with PAIS. If successful, the study could identify a readily available oral treatment for a condition with limited therapeutic options and contribute to improving the care of individuals living with persistent symptoms after infection.

Tipo di studio

Interventistico

Iscrizione (Stimato)

138

Fase

  • Fase 2

Contatti e Sedi

Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.

Contatto studio

Backup dei contatti dello studio

Luoghi di studio

  • Germania
    • State of Berlin
      • Berlin, State of Berlin, Germania, 10117

Criteri di partecipazione

I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.

Criteri di ammissibilità

Età idonea allo studio

  • Adulto
  • Adulto più anziano

Accetta volontari sani

No

Descrizione

Inclusion Criteria:

  • 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):

    1. Confirmed post-menopausal state, defined as amenorrhea for at least 12 months, or
    2. 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%)

Exclusion Criteria:

  • 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)

Piano di studio

Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.

Come è strutturato lo studio?

Dettagli di progettazione

  • Scopo principale: Trattamento
  • Assegnazione: Randomizzato
  • Modello interventistico: Assegnazione incrociata
  • Mascheramento: Quadruplicare

Armi e interventi

Gruppo di partecipanti / Arm
Intervento / Trattamento
Comparatore attivo: Aripiprazole (low-dose, 1mg)
Tested IMP: Aripiprazole (low-dose, over-encapsulated). Authorization status: Not authorized in this targeted therapeutic indication; aripiprazole is authorized for treatment of multiple psychiatric diseases. The tablets administered in this trial are a commercially available medicinal product manufactured by Sawai Pharmaceutical Co., Ltd., with marketing authorisation number 1179045F8036. Administration: Participants will take one overencapsulated tablet containing 1 mg of aripiprazole orally every other day for the first two weeks (titration phase), followed by once-daily administration for six weeks. The treatment period consists of two consecutive 8-week periods of blinded investigational medicinal product (IMP) administration: 8 weeks of active comparator followed by 8 weeks of placebo (Sequence A), or 8 weeks of placebo followed by 8 weeks of active comparator (Sequence B).
Droga: Aripiprazole (low-dose, 1mg)
The treatment period consists of two consecutive 8-week periods of blinded IMP administration: 8 weeks of aripiprazole followed by 8 weeks of placebo (Sequence A), or 8 weeks of placebo followed by 8 weeks of aripiprazole (Sequence B). Follow-up assessments will be conducted after each treatment period, at Weeks 9 and 19 of the study.
Comparatore placebo: Placebo
Comparator IMP: Placebo (over-encapsulated tablet). Authorization status: Authorized medicinal product without a specific therapeutic indication. The placebo tablets administered in this trial are commercially available P-Tabletten Lichtenstein marketed by Zentiva Pharma GmbH. To ensure identical conditions and maintain blinding, both the active comparator (aripiprazole) and placebo tablets will be overencapsulated and provided in identical packaging. Administration: Participants will take one overencapsulated placebo tablet orally every other day for the first two weeks (titration phase, to ensure the same dosing schedule as for the active comparator), followed by once-daily administration for six weeks. The treatment period consists of two consecutive 8-week periods of blinded IMP administration: 8 weeks of active comparator followed by 8 weeks of placebo (Sequence A), or 8 weeks of placebo followed by 8 weeks of active comparator (Sequence B).
Droga: Placebo
The treatment period consists of two consecutive 8-week periods of blinded IMP administration: 8 weeks of active comparator followed by 8 weeks of placebo (Sequence A), or 8 weeks of placebo followed by 8 weeks of active comparator (Sequence B).
Altri nomi:
  • P-Tabletten Lichtenstein

Cosa sta misurando lo studio?

Misure di risultato primarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Intra-patient change in the Chalder Fatigue Scale (CFQ) by ≥ 3 points from baseline to week 9 in patients with PAIS.
Lasso di tempo: 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.
9 weeks after first IMP intake

Misure di risultato secondarie

Misura del risultato
Misura Descrizione
Lasso di tempo
Intra-patient change in CFQ by ≥3 points from baseline to week 9 in the subgroup fulfilling ME/CFS criteria.
Lasso di tempo: 9 weeks after first IMP intake
@Studyteam: Please add a description of how the ME/CFS subgroup is defined in this trial.
9 weeks after first IMP intake
Intra-patient change in CFQ from baseline to week 19 and from week 9 to week 19.
Lasso di tempo: 9 and 19 weeks after first IMP intake
The within-patient change in physical and mental fatigue, as measured by the CFQ, will be assessed 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.
Lasso di tempo: 9 and 19 weeks after first IMP intake
The FSS is a 9-item scale that assesses fatigue severity and its impact on a person's activities and lifestyle. Each item is rated on a 7-point scale (1 = strongly disagree; 7 = strongly agree), resulting in a total score ranging from 9 (no fatigue) to 63 (severe fatigue). The within-patient change in fatigue severity will be assessed from baseline to week 9, 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 Bell Disability Scale from baseline to week 9 and to week 19 and from week 9 to week 19
Lasso di tempo: 9 and 19 weeks after first IMP intake
The Bell Disability Scale is a standard assessment tool used to evaluate functional ability in adults with ME/CFS. It comprises 11 statements describing the patient's functional status, including symptom severity at rest and during activity, overall activity level, and the ability to work, travel, and perform self-care activities. Scores range from 0 (bedridden) to 100 (no symptoms and fully functional). The within-patient change in functional ability will be assessed from baseline to week 9, 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 PROMIS-29 questionnaire from baseline to week 9 and to week 19 and from week 9 to week 19.
Lasso di tempo: 9 and 19 weeks after first IMP intake
The PROMIS-29 is a patient-reported outcome measure that assesses physical, mental, and social health. It can be used in both the general population and individuals with chronic health conditions. The within-patient changes in the health domains assessed by the PROMIS-29 will be assessed from baseline to week 9, 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 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
Lasso di tempo: 9 and 19 weeks after first IMP intake
The Short Form 36 Health Survey (SF-36) is an established and widely used measure of health-related quality of life. The Physical Functioning (PF) domain assesses limitations in ten activities related to mobility and self-care, such as walking specified distances, carrying groceries, bathing, and dressing. Scores are weighted and transformed to a scale ranging from 0 (severe functional limitations) to 100 (no functional limitations). The within-patient change in SF-36 PF will be assessed from baseline to week 9, 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 Multifactorial Memory Questionnaire (MMQ) subscale memory satisfaction from baseline to week 9 and to week 19 and from week 9 to week 19
Lasso di tempo: 9 and 19 weeks after first IMP intake
The MMQ is a participant-reported outcome measure that assesses different aspects of subjective memory functioning. It comprises three subscales assessing memory satisfaction, perceived memory ability, and the use of memory strategies. The MMQ memory satisfaction subscale consists of 18 items rated on a 5-point Likert scale based on the participant's experiences during the previous two weeks. Scores range from 0 to 72, with higher scores indicating greater satisfaction with memory. A change of 13 points is considered clinically meaningful. The within-patient change in memory satisfaction will be assessed from baseline to week 9, 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 Becks Depression Inventory (BDI-II) from baseline to week 9 and to week 19 and from week 9 to week 19
Lasso di tempo: 9 and 19 weeks after first IMP intake
The BDI-II is a widely used self-report questionnaire that assesses the severity of depressive symptoms in individuals aged 13 years and older. It consists of 21 items, each assessing a specific symptom of depression. Each item is rated on a scale from 0 to 3, with higher total scores indicating greater severity of depressive symptoms. The within-patient change in the severity of depressive symptoms will be assessed from baseline to week 9, 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 Post Exertional Malaise (PEM) questionnaire from baseline to week 9 and to week 19 and from week 9 to week 19
Lasso di tempo: 9 and 19 weeks after first IMP intake
The PEM questionnaire assesses the frequency, severity, and duration of PEM. Frequency and severity scores each range from 0 to 20, with higher scores indicating more frequent and more severe PEM, respectively. Duration scores range from 0 to 6, with higher scores indicating longer-lasting PEM. The within-patient change in PEM frequency, severity, and duration will be assessed from baseline to week 9, 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 Somatic Symptom Disorder-B Criteria Scale (SSD-12) from baseline to week 9 and to week 19 and from week 9 to week 19
Lasso di tempo: 9 and 19 weeks after first IMP intake
The SSD-12 is a 12-item self-report questionnaire that assesses the psychological features associated with somatic symptom disorder according to the DSM-5 B criteria. It assesses cognitive, affective, and behavioral responses to somatic symptoms, with four items covering each domain. Each item is rated on a 5-point scale from 0 to 4, resulting in a total score ranging from 0 to 48. Higher scores indicate greater psychological distress and symptom-related thoughts, feelings, and behaviors associated with somatic symptoms. The within-patient change in psychological responses to somatic symptoms will be assessed from baseline to week 9, from baseline 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).
Lasso di tempo: 9 and 19 weeks after first IMP intake
The occurrence of adverse reactions and other safety events, including but not limited to infections, endocrine disorders, and psychiatric complications, will be assessed based on AE, SAE, and SUSAR reporting.
9 and 19 weeks after first IMP intake

Collaboratori e investigatori

Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.

Sponsor

Christiana Franke

Investigatori

  • Investigatore principale: Christiana Franke, PD MD, Charite University, Berlin, Germany

Studiare le date dei record

Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.

Studia le date principali

Inizio studio (Stimato)

1 ottobre 2026

Completamento primario (Stimato)

15 maggio 2028

Completamento dello studio (Stimato)

31 dicembre 2028

Date di iscrizione allo studio

Primo inviato

15 luglio 2026

Primo inviato che soddisfa i criteri di controllo qualità

15 luglio 2026

Primo Inserito (Effettivo)

20 luglio 2026

Aggiornamenti dei record di studio

Ultimo aggiornamento pubblicato (Effettivo)

20 luglio 2026

Ultimo aggiornamento inviato che soddisfa i criteri QC

15 luglio 2026

Ultimo verificato

1 luglio 2026

Maggiori informazioni

Termini relativi a questo studio

Parole chiave

Termini MeSH pertinenti aggiuntivi

Altri numeri di identificazione dello studio

  • PAISE-AriSE

Informazioni su farmaci e dispositivi, documenti di studio

Studia un prodotto farmaceutico regolamentato dalla FDA degli Stati Uniti

No

Studia un dispositivo regolamentato dalla FDA degli Stati Uniti

No

Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .

Prove cliniche su Post-acute Infectious Syndrome (PAIS)

Prove cliniche su Aripiprazole (low-dose, 1mg)

Cerca prove simili

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

CROs by country

CROs in Albania

Condizioni

Malattie rare

Interventi farmacologici

Supplementi dietetici

Sponsor / Collaboratori

Sedi

3
Sottoscrivi