NCT03574948.

Trial name or title	Multicentric, double‐blind, placebo controlled clinical trial with 5‐hydroxytryptophan (5‐HTP) in patients with inflammatory bowel disease in clinical and biologic remission: effect on fatigue scores
Methods	A phase 2, multicentred, double‐blind, randomised placebo‐controlled trial, cross‐over assignment
Participants	Adults (aged 18 ‐ 60 years) with a documented diagnosis of Crohn's disease or ulcerative colitis in clinical remission over 3 months (physical global assessment; SCCAI ≤ 2 for ulcerative colitis or Harvey Bradshaw index ≤ 4 for Crohn's disease) reporting fatigue (score 5 or more on a 1 ‐ 10 visual analogue scale). Treated with biologicals and/or immunosuppressives since at least 6 months with stable dose over last 3 months and in biologic remission at day 0 (CRP < 10 mg/L and faecal calprotectin value < 250 mg/kg)
Interventions	Experimental: 5‐HTP ‐ 8 weeks active substance 5‐HTP (2 x 100 mg per day) Placebo comparator: 8 weeks placebo oral capsule (2 x 1 capsule per day)
Outcomes	Primary outcome: Fatigue (visual analog scale) Secondary outcome: Fatigue (FACIT‐F); Depression (short Depression Anxiety and Stress Scale); Physical activity (Adapted International Physical Activity Questionnaire); serum 5‐HydroxyTryptophane (5‐HTP); serum 5‐hydroxyindoleacetic acid; serum serotonin levels; serum melatonin levels; faecal microbiome/metabolome
Starting date	December 2018
Contact information	Dr Martine De Vos 0032 9 332 23 71 martine.devos@uzgent.be Dr Triana Lobaton Ortega 0032 9 332 23 89 Triana.LobatonOrtega@UZGENT.be
Notes	Estimated study completion date:December 2020 Estimated enrollment: 180 participants

^{5‐HTP: 5‐hydroxytryptophan
 AF:
 ALT: alanine transaminase
 AP: Abdominal pain
 AST: Aspartate transaminase
 BDI‐II: Beck Depression Inventory
 BIA: Bioelectrical impedance analysis
 BMI: Body Mass Index
 CCI: Comprehensive complication index
 CD: Crohn's disease
 CDAI: Crohn's Disease Activity Index
 CD‐PRO: Crohn's disease ‐ Patient Reported Outcomes
 CIS‐20: Checklist Individual Strength ‐ 20
 CRP: C‐reactive protein
 CSS:Crohn's Symptoms Severity
 CT: Computerised tomography
 DXA: Dual‐energy X‐ray absorptiometry
 ED: Emergency department
 ER: Emergency room
 ESR: Erythrocyte sedimentation rate
 EVOO: extra virgin olive oil
 FACIT‐F: Functional Assessment of Chronic Illness Therapy ‐ Fatigue
 FBC: Full blood count
 FC: Faecal calprotectin
 fl: femtolitre
 FR‐QoL‐29: Food‐related quality of life
 GAD: Generalised Anxiety Disorder
 GI: Gastrointestinal
 GOS: Galacto‐oligosaccharides
 HAD: Hospital Anxiety and Depression
 Hbg: Hemoglobin
 HBI: Harvey Bradshaw Index
 Ht: hematocrit
 IBD: Inflammatory bowel disease
 IBD‐F: Inflammatory Bowel Disease ‐ Fatigue
 IBDQ: Inflammatory Bowel Disease Questionnaire
 IBDU: Inflammatory bowel disease unclassified
 IFN‐y: interferon gamma
 IgA: Immunoglobulin A
 IL: Interleukin
 IU: International units
 IV: Intravenous
 LPS: Lipopolysaccharidde
 LTE: Long‐term extension
 mg: milligram
 mg/kg: milligram per kilogram
 MFI: Multidimensional Fatigue Inventory
 PCD: Paediatric Crohn's disease
 PCDAI: Paediatric Crohn's Disease Activity Index
 PCT: Procalcitonin
 PedsQL: Pediatric Quality of Life Inventory
 PGR‐C: Patient Global rsting ‐ Change}

^{PGR‐S: Patient Global Rating ‐ Severity
 PHQ15: Patient Health Questionnaire 15
 POD: Postoperative day
 PROMIS: Patient‐Reported Outcomes Measurement Information System
 PUCAI: Pediatric Ulcerative Colitis Activity Index
 Q4: 4 weekly}

^{Q8: 8 weekly}

^{Q12: 12 weekly
 QOLITI: Quality of Life Tool for IBD
 RCT: Randomised controlled trial
 retHb: reticulocyte hemoglobin
 rRNA: Ribosomal ribonucleic acid
 SC: Subcutaneous
 SCCAI: Simple Clinical Colitis Activity Index
 SES‐CD: Simple Endoscopic Score for Crohn's Disease
 SF: Stool Frequency
 SF‐36:36‐Item Short Form
 SIBDQ: Short Inflammatory Bowel Disease Questionnaire
 SPCDAI:Short Pediatric Crohn's Disease Activity Index
 SSIs:surgical site infections 
 STAI: State‐Trait Anxiety Inventory 
 sTfR:soluble transferrin receptors}

^{sTfR(‐F): soluble transferrin receptors to log ferritin
 STPI: State‐Trait Personality Inventory
 TB: Tuberculosis
 TNFα: Tumor necrosis factor alpha
 TNFr1: Tumor necrosis factor receptor 1
 T2T:Treat‐to‐Target
 UC: Ulcerative colitis
 UC‐SQ: Ulcerative Colitis Symptom Questionnaire
 UST: Ustekinumab
 VAS: Visual Analogue Scale
 VO2: maximal oxygen uptake
 WBC: White blood cells
 wk: week
 WLC: Waiting‐list control}