Modafinil for Debilitating Fatigue in Quiescent Inflammatory Bowel Disease MODIFI-IBD Trial)

Inclusion Criteria:

* Willing and able to provide signed informed consent at the screening visit as well as comply with all study visits and requirements through the end of the study
* Age between 18 to 75 years at screening.
* ≥1 year diagnosis of IBD, based on a combination of clinical, endoscopic, histologic and radiologic criteria
* Chronic fatigue for at least six months
* Severe fatigue as confirmed with a score of ≥11 on section I of the IBD-F
* Clinically quiescent IBD with a Harvey Bradshaw Index (HBI) <5 for CD patients or a Simple Colitis Clinical Activity Index (SCCAI) ≤2 for patients with UC or IBD-unclassified
* Faecal calprotectin <250 µg/g
* Stable IBD medication for ≥3 months before screening visit and no change in IBD medication planned for ≥3 months

Exclusion Criteria:

* Contraindications for the use of modafinil, such as:

  * Uncontrolled hypertension
  * Cardiac arrhythmia
  * A history of left ventricular hypertrophy or cor pulmonale, and in patients with mitral valve prolapse who have previously developed mitral valve prolapse syn-drome during treatment with central nervous system stimulants
  * Patients with hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption
* Patients using medication which interacts clinically significant with modafinil, see section 3.3 'Mechanism of action \& Drug class'
* Patients using pharmacological agents with similar effects to modafinil, like central nerv-ous system (CNS) stimulants or other wakefulness-promoting drugs such as methylphenidate and amphetamines
* Surgery before or during study period that impacts ability to participate in this study, per investigator judgement
* Participation in another intervention study (excl. registries and post marketing studies)
* Pregnancy or nursing at the moment of screening or planned pregnancy within two months after last dose
* People with a diagnosis of drug or alcohol dependence syndrome will be excluded
* Comorbidities or confirmed diagnoses known to cause fatigue, which may influence study outcomes, including but not limited to:

  * Anaemia (Hb <7.0 mmol/l for women and <8.0 mmol/l for men) and which is judged as clinically significant by the investigator
  * Folate deficiency (<6.0 nmol/l)
  * Iron deficiency (ferritin <20 g/l for women and <25 g/L for men)
  * Vitamin B12 deficiency (<148 pmol/l)
  * Liver insufficiency defined by an ALT or AST >2x ULN or total bilirubin > 2 mg/dL
  * Renal insufficiency defined by an estimated glomerular filtration rate < 45 mL/min, calculated using the Chronic Kidney Disease-Epidemiology Collaboration equation and/or a serum creatinine >178 μmol/L (2mg/dL)
  * Auto-immune disorders such as primary sclerosing cholangitis, rheumatoid ar-thritis, systemic lupus erythematosus or coeliac disease
  * Uncontrolled or recently diagnosed depression
  * Active suicidal ideation
  * Bipolar disorder
  * Schizophrenia or other psychotic disorders
  * Other psychiatric disorders that may interfere with the study as judged by the investigators
  * History or current anxiety or sleep disorders
  * Substance dependence disorders (e.g. alcohol, cannabis, drugs)
  * Evidence, history, or suspicion of infectious diseases that may interfere with the study as judged by the investigators
  * Active Epstein-Barr virus or cytomegalovirus infection
  * Endocrinological disorders such as uncontrolled diabetes mellitus, untreated hy-pothyroidism, hypoadrenalism or hypogonadism
  * Neurological disorders such as multiple sclerosis, dementia, Parkinson's disease or myasthenia gravis
  * Heart failure
  * Chronic obstructive pulmonary disease
  * Obstructive sleep apnoea
  * Active malignancy (exception of malignancies adequately treated with resection for non-metastatic basal cell carcinoma)
  * Long/post-COVID
* Patients who are not able to complete the Dutch questionnaires in an online form
* Has a clinically significant concurrent disease or relevant laboratory abnormality or a history of illness or medical condition that in the investigator's opinion could confound the study results or increase the participant's risk by taking part in the study