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

NCT07714213 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: PAISE-AriSE
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Post-acute Infectious Syndrome (PAIS); Post-COVID-19 Condition (PCC or Long COVID)

Keywords

PAIS; Long COVID; Fatigue; Cognitive deficits

Outcome Measures

Primary Outcomes (1)

• Intra-patient change in the Chalder Fatigue Scale (CFQ) by ≥ 3 points from baseline to week 9 in patients with PAIS.

  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

Secondary Outcomes (11)

• 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

Study Arms (2)

Aripiprazole (low-dose, 1mg)

ACTIVE COMPARATOR

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).

Drug: Aripiprazole (low-dose, 1mg)

Placebo

PLACEBO COMPARATOR

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).

Drug: Placebo

Interventions

Aripiprazole (low-dose, 1mg) DRUG

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.

Aripiprazole (low-dose, 1mg)

Placebo DRUG

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).

Also known as: P-Tabletten Lichtenstein

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%)

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Christiana Franke: lead

Study Sites (1)

Charité - Universitätsmedizin Berlin

Berlin, State of Berlin, 10117, Germany

Location

MeSH Terms

Conditions

Hemophilia B; Post-Acute COVID-19 Syndrome; Fatigue; Cognition Disorders

Interventions

Aripiprazole

Condition Hierarchy (Ancestors)

Blood Coagulation Disorders, Inherited; Blood Coagulation Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Coagulation Protein Disorders; Hemorrhagic Disorders; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, X-Linked; COVID-19; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases; Post-Infectious Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Christiana Franke, PD MD

  Charite University, Berlin, Germany

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christiana Franke, PD MD

CONTACT

+49 30 450 560883; christiana.franke@charite.de

Fabian R Bösl, MD

CONTACT

+49 30 450 560822; fabian.boesl@charite.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior physician

Model Details: Prospective double-blind, placebo-controlled randomized phase 2a trial with cross-over design.

Study Record Dates

• First Submitted: July 15, 2026
• First Posted: July 20, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): May 15, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 20, 2026

Record last verified: 2026-07

Locations

DE (1)