5-HTP in Patients With IBD in Clinical and Biologic Remission:Effect on Fatigue Scores

Study Overview
=================
Brief Summary
-----------------
This placebo cross-over trial aims to study the effect of the oral intake of an essential amino-acid 5-OH tryptophan, the precursor of serotonin, on the fatigue scores in IBD patients in deep clinical and biological remission.

Official 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

Conditions
-----------------
Crohn Disease, Ulcerative Colitis, Fatigue, Remission

Intervention / Treatment
-----------------
* Drug: 5-HTP
* Drug: Placebo oral capsule


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: The subject is male or female and aged 18 to 60 yrs (inclusive) The subject has a documented Crohn's disease or ulcerative colitis The subject is, in the opinion of the investigator, capable of understanding and complying protocol requirements The subject is in clinical remission over last 3 months (based on physician global assessment) The subject is in clinical remission at day 0 based on validated scores (SCCAI ≤ 2 for ulcerative colitis or Harvey Bradshaw index ≤ 4 for Crohn's disease). The subject reports fatigue on a quantified scale (visual analogue scale 0 - 10) of 5 or more The subject is treated with biologicals and/or immunosuppressives since at least 6 months with stable dose over last 3 months The subject is in biologic remission at day 0: CRP < 10 mg/l and faecal calprotectin value < 250 mg/kg Exclusion Criteria: The subject has a clinical validated depression The subject is taking antidepressives or neuroleptics The subject has a psychiatric comorbidity The subject has important comorbidities: cardiovascular disease, obstructive lung pathology, neoplasia or other The subject has a documented Anemia (based on lab results including Hb < 12-13 g/dl respectively for saturation index < 20%, Vit B12 < 148 pmol/L or folic acid < 6 nmol/L) The subject has a documented hypothyreoidea (documented by a recent lab result including TSH) The subject reports an infection within 2 weeks before inclusion The subject reports any change in IBD medication (biologicals and immunosuppressives) in the last 12 weeks before inclusion The subject was treated with oral corticosteroids during the last 8 weeks before enrolment The subject reports an ongoing pregnancy or breastfeeding The subject has a history of lymphoproliferative disease or cancer other than basocellular skin cancer The subject underwent surgery in the past 12 weeks prior to the screening visit The subject reports a history of clinically significant drug abuse (defined as any illicit drug use) or alcohol abuse within 1 year prior to inclusion

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-HTP<br>8 weeks active substance 5-HTP (2 x 100 mg per day) | Drug: 5-HTP<br>* 8 weeks active substance 5-HTP (2 x 100mg per day)<br>* Other names: Levotonine;|
| Placebo Comparator: placebo oral capsule<br>8 weeks placebo (2 x 1 capsule per day) | Drug: Placebo oral capsule<br>* 8 weeks placebo (2 x 1 caps per day)<br>* Other names: placebo;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Visual Analog Scale (VAS) after intervention | Patients are asked to indicate their fatigue level on a VAS-scale from 0 to 10, where 0 represents no fatigue and where 10 indicates the patient suffers from severe fatigue. | weekly, 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) score | The questionnaire is a self-assessment that need to be completed without external help. The FACIT-F questionnaire measures the fatigue of the patient and will be filled in at week 0, week 8 and week 16. The FACIT Fatigue scale ranges from 0 to 52, with high scores indicating higher levels of fatigue. | week 0, week 8 and week 16 | 
| Changes in short Depression Anxiety and Stress Scale (DASS21) | The questionnaire is a self-assessment that need to be completed without external help. The DASS questionnaire measures depression and anxiety and will be filled in at week 0, week 8 and week 16. The questionnaire contains 7 items per scale, the maximum score for depression, anxiety and stress will be 21. The higher the score of the questionnaire, the more the patient suffers from depression, anxiety and stress. | week 0, week 8 and week 16 | 
| Change in Adapted International Physical Activity Questionnaire (IPAQ) | The adapted IPAQ questionnaire measures the physical activity and will be filled in at week 0, week 8 and week 16. | week 0, week 8 and week 16 | 
| Changes in serum 5-HydroxyTryptophane (5-HTP) by treatment | The possible effect of Levotonine administration on the serum 5-HTP levels will be measured. | Week 0, week 8 and week 16 | 
| Changes in serum 5-hydroxyindoleacetic acid by treatment | The possible effect of Levotonine administration on the serum 5-hydroxyindoleacetic levels will be measured. | Week 0, week 8 and week 16 | 
| Changes in serum serotonin levels by treatment | The possible effect of Levotonine administration on the serum serotonin levels will be measured. | Week 0, week 8 and week 16 | 
| Changes in serum melatonin levels by treatment | The possible effect of Levotonine administration on the serum melatonin levels will be measured. | Week 0, week 8 and week 16 | 
| Changes in faecal microbiome/metabolome | since the intestinal bacteria can process tryptophane, changes in the faecal microbiome/metabolome can be possibly caused by the administration of levotonine. | Week 0, week 8 and week 16 |