Post-acute Infectious Syndrome - Aripiprazole Symptom Evaluation (PAIS-AriSE) | NCT07714213

NCT07714213

Overview

NCT ID: NCT07714213
Lead Sponsor: Christiana FrankeOTHER
Official Title: 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)
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

Status and Timeline

Status: Not yet recruiting
Last Update Posted: Jul 20, 2026Actual
Start Date: Oct 1, 2026Estimated
Primary Completion Date: May 15, 2028Estimated
Completion Date

Participation Criteria

Ages Eligible for Study: Adult (18-64)Older Adult (65+)
Sexes Eligible for Study: All
Accepts Healthy Volunteers?: No
Eligibility Criteria: 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):

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%)

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)

Study Plan

Study Type: Interventional
Phase: Phase 2
Enrollment: 138Estimated
Primary Purpose: Treatment
Allocation: Randomized
Interventional Model: Crossover Assignment
Masking: Quadruple

Contacts and Locations

Central Contacts: Christiana Franke, PD MDContact
christiana.franke@charite.de+49 30 450 560883

Similar Studies

Participant Group/Arms

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)

PlaceboPlacebo 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).