E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Functional Dyspepsia (FD) |
Functionele dyspepsie (FD) |
|
E.1.1.1 | Medical condition in easily understood language |
Patients with dyspepsia or symptoms of indigestion, for which no structural cause is found after routine upper gastrointestinal endoscopy |
Patiënten met dyspepsie of verteringsklachten, waarvoor geen structurele oorzaak is gevonden na routine gastrocopie |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Digestive System Diseases [C06] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the effect of Proton Pump Inhibitors (PPI) on the duodenal, oral and fecal microbiota composition in FD patients before and after start PPI during 4 weeks (FD cohort 1) |
Om het effect van proton pomp inhibitoren (PPI) op het duodenale, orale en fecale microbioom te bestuderen in 2 aparte FD cohorten: voor en na start PPI gedurende 4 weken (FD cohorte 1) |
|
E.2.2 | Secondary objectives of the trial |
Correlate changes in the microbiota with clinical response, bile acids, intestinal permeability, mucosal inflammation, salivary cortisol levels and blood high sensitivity-CRP. |
Correleren van veranderingen in microbioom met klinische respons, galzouten, intestinale permeabiliteit, mucosale inflammatie, cortisol in speeksel en hs-CRP in bloed. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Patients with FD diagnosis as per Rome IV criteria - Endoscopy needed as part of routine practice - Subjects aged between 18 and 64 years inclusive - Male or female (not pregnant or lactating and using contraception or postmenopausal in FD cohort 1 only) - Normal bowel habits (defecation once every 3 days up to 3 times a day) - Witnessed written informed consent - Access to home freezer (-18 to -20°C) - Capable to understand and comply with the study requirements |
- Patiënten met diagnose van FD volgens Rome IV criteria -Gastroscopie nodig als onderdeel van klinische praktijk -18 tot en met 64 jaar -man en vrouw (niet zwanger, geen borstvoeding en gebruik van contraceptie of postmenopauzaal voor FD cohorte 1) - Normale stoelgangsfrequentie (minimaal 1x om de 3 dagen, maximaal 3x per dag) - Toegang tot een diepvries thuis (minimaal -18°C) voor bewaring van de stalen -Ondertekend toestemmingsformulier - In staat om de studie vereisten te begrijpen en na te leven |
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E.4 | Principal exclusion criteria |
- Any active somatic or psychiatric condition that can explain the dyspeptic symptoms (stable dose of single antidepressant allowed) - Predominant symptoms of gastro-esophageal reflux disease (GERD) or irritable bowel syndrome (IBS) - Use of immunosuppressants or antibiotics within 3 months before sampling - Use of drugs influencing gut motility or stool consistency, NSAIDs, anti-allergy drugs, bile acid sequestrants or ursodeoxycholic acid within 2 weeks before sampling - History of major abdominal surgery, including cholecystectomy but not appendectomy -Personal or family (first-degree relative) history of diabetes mellitus type 1, celiac disease, inflammatory bowel disease, psoriasis, rheumatic or other auto-immune diseases (including therapy) -Allergy or atopy (eczema, asthma and/or allergic rhinoconjunctivitis) (including therapy) -Kidney, liver or coagulation disorders -Active coronary or peripheral artery disease -Diabetes mellitus type 2 (including therapy) - Active malignancy (including therapy) -Known HIV, HBV or HCV infection (including therapy) - Magnetizable objects (e.g. cochlear implants, neural stimulator, pacemaker, metal fragments or implants) or claustrophobia (MRI safety criteria, other procedures can still take place) - Significant alcohol use (>10 units/weeks) - Any use of alcohol or smoking in the 2 days before sampling - Females who are pregnant or lactating, who are not using contraception and premenopausal (FD cohort 1 only) - Allergy or intolerance to PPI (FD cohort 1 only) |
- Patiënten met een actieve medische of psychiatrische aandoening welke de klachten kan verklaren (stabiele dosis van 1 antidepressivum toegelaten) - Patiënten met overwegend klachten van zuurbranden en/of prikkelbare darmsyndroom - Inname van medicatie die het afweersysteem onderdrukken of antibiotica minder dan 3 maanden voor staalname - Inname van medicatie die de darmwerking of stoelgangsconsistentie beïnvloedt, ontstekingsremmers, anti-allergie medicatie, anionen-uitwisselaars (Questran® of Colestid ®) of ursodeoxycholzuur (Ursofalk® of Ursochol®) minder dan 2 weken voor staalname - Patiënten met in het verleden een grote maag- of darmoperatie, inclusief verwijdering van de galblaas maar niet de appendix of blinde darm - Persoonlijke of familiale (eerstegraads familielid) voorgeschiedenis van diabetes mellitus type 1 (= auto-immuun gemedieerde vorm van suikerziekte), coeliakie (= glutenallergie), inflammatoir darmlijden, psoriasis, reumatische of auto-immuunaandoeningen - Patiënten met allergie of atopie (eczeem, astma, allergische rhinoconjunctivitis) of behandeling hiervoor - Patiënten met nier-, lever- of stollingsproblemen - Patiënten met actief coronair of perifeer vaatlijden - Patiënten met type 2 diabetes mellitus of behandeling hiervoor - Patiënten met actieve maligniteit of behandeling hiervoor - Patiënten met gekende HIV, hepatitis B of C infectie of behandeling hiervoor - Patiënten met magnetiseerbare metalen voorwerpen in hun lichaam (bv. hoorimplantaat, metalen fragmenten of prothesen, pacemaker of neurostimulator) of claustrofobie (enkel voor MRI, andere procedures kunnen doorgaan) - Overmatig alcoholgebruik (>10 eenheden/week) - Gebruik van alcohol of roken in de 2 dagen voor staalname - Vrouwen die zwanger zijn, borstvoeding geven of geen contraceptie gebruiken en premenopauzaal zijn (cohorte 1) - Allergie of intolerantie voor PPI (cohorte 1) |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Microbiota composition of the duodenum, feces and saliva |
Bacteriële samenstelling van het duodenum, stoelgang en speeksel |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Study inclusion, after baseline period of 4 weeks and after treatment with Pantomed 40mg once daily for 4 weeks (FD cohort 1) |
Bij inclusie in de studie, bij vervroegde controle na 4 weken en na behandeling met Pantomed 40mg éénmaal daags gedurende 4 weken (FD cohort 1) |
|
E.5.2 | Secondary end point(s) |
Clinical response, bile acids, intestinal permeability, mucosal inflammation, salivary cortisol and blood hs-CRP |
Klinsche respons, galzouten, intestinale permeabiliteit, mucosale inflammatie, cortisol in speeksel en hs-CRP in bloed |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Study inclusion, after baseline period of 4 weeks and after treatment with Pantomed 40mg once daily for 4 weeks (FD cohort 1) |
Bij inclusie in de studie, bij vervroegde controle na 4 weken en na behandeling met Pantomed 40mg éénmaal daags gedurende 4 weken (FD cohort 1) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
To assess alterations of the duodenal, oral and fecal microbiota composition with PPI in FD patients |
Om veranderingen in de duodenale, orale en fecale bacteriële samenstelling met PPI te bestuderen in FD patiënten |
|
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |