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

Prior treatment

• 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

Other illness

• People with a diagnosis of drug or alcohol dependence syndrome will be excluded

Lab values

• 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
• 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
• 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

Other

• 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
• Patients who are not able to complete the Dutch questionnaires in an online form

• 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