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

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)

Interventions

DRUG

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.

DRUG

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).

Sponsors & Collaborators

• Christiana Franke

  lead OTHER

Principal Investigators

• Christiana Franke, PD MD · Charite University, Berlin, Germany

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-01

Primary Completion

2028-05-15

Completion

2028-12-31

Countries

• Germany

Study Locations