SINBAD: Sequestrant in Bile Acid Diarrhoea 2019 Jan 4th version 6.0 SINBAD Treatment effect of colesevelam for bile acid diarrhoea – a randomised placebo-controlled trial. Danish Region Zealand scientific ethics committee: SJ-641 EudraCT number: 2016-001452-22 SJ-641 EudraCT number: 2016-001452-22 Page 1 of 30 SINBAD: Sequestrant in Bile Acid Diarrhoea 2019 Jan 4th version 6.0 TABLE of CONTENTS Primary research group.................................................................. Fejl! Bogmærke er ikke defineret. Study locations ..................................................................................................................................... 4 Monitoring ........................................................................................................................................... 5 Abbreviations ....................................................................................................................................... 5 Aim ....................................................................................................................................................... 6 Summary of expected improvements from the study ........................................................................ 6 Background .......................................................................................................................................... 6 Bile acid diarrhoea ....................................................................................................................... 6 Present diagnosis of bile acid diarrhoea ...................................................................................... 7 Biochemical markers of bile acid diarrhoea ................................................................................ 7 Biochemical tests in our population – choice of C4 cutoff .......................................................... 8 Treatment of Bile Acid Diarrhoea ................................................................................................ 9 Design ................................................................................................................................................. 10 Study subjects ............................................................................................................................ 10 Inclusion criteria ......................................................................................................................... 10 Exclusion criteria ........................................................................................................................ 10 Endpoints ........................................................................................................................................... 11 Primary endpoint ....................................................................................................................... 11 Secondary endpoints ................................................................................................................. 11 Descriptive endpoints and ancillary analytic endpoints ............................................................ 12 Ancillary endpoints for Patient Reported Outcomes ................................................................. 12 Power calculation ............................................................................................................................... 13 Methods ............................................................................................................................................. 13 Bristol stool form scale .............................................................................................................. 13 Response criteria in chronic watery diarrhoea – Hjortswangs criteria ..................................... 13 Patient reported outcomes ........................................................................................................ 14 Blinding............................................................................................................................................... 15 Emergency unblinding ............................................................................................................... 15 Randomisation ................................................................................................................................... 16 Biochemistry ...................................................................................................................................... 16 Biobank .............................................................................................................................................. 16 Study medication ............................................................................................................................... 16 Colesevelam ............................................................................................................................... 16 SJ-641 EudraCT number: 2016-001452-22 Page 2 of 30 SINBAD: Sequestrant in Bile Acid Diarrhoea 2019 Jan 4th version 6.0 Placebo ....................................................................................................................................... 18 Study plan........................................................................................................................................... 19 Pre-screening – Written invitation............................................................................................. 19 Study visit 1 – Inclusion and start of baseline registration ........................................................ 19 Study visit 2 – Assessment of eligibility by stool diary results ................................................... 21 Telephone consultation: Start of intervention .......................................................................... 22 Telephone consultation: Start of endpoint period – compliance and AEs ................................ 23 Study visit 3 – Treatment end and repeated questionnaires (Q-int) ......................................... 23 End of the clinical study phase................................................................................................... 23 Six-month follow-up ................................................................................................................... 24 Adverse events ................................................................................................................................... 24 Schedule ............................................................................................................................................. 24 Rights .................................................................................................................................................. 24 Planned publications .......................................................................................................................... 25 Ethics .................................................................................................................................................. 25 Recruiting ........................................................................................................................................... 25 Information and consent ........................................................................................................... 25 Results ........................................................................................................................................ 26 Risks and nuisances .................................................................................................................... 26 Data security and access .................................................................................................................... 26 Data from the participants’ medical chart ................................................................................. 27 Primary data responsibility .................................................... Fejl! Bogmærke er ikke defineret. Investigators with data access for analysis ............................ Fejl! Bogmærke er ikke defineret. Economy ............................................................................................................................................. 27 Compensation and insurance in case of injury caused by the study ......................................... 27 References.......................................................................................................................................... 27 Appendix 1: Study overview chart ..................................................................................................... 30 SJ-641 EudraCT number: 2016-001452-22 Page 3 of 30 SINBAD: Sequestrant in Bile Acid Diarrhoea 2019 Jan 4th version 6.0 Study locations Zealand University Hospital Department of Internal Medicine, Section of Gastroenterology Lykkebækvej 1, DK-4600 Køge Hvidovre University Hospital: Gastro-Unit, Medical Division DK-2650 Hvidovre, Kettegårds Allé 30, DK-2650 Hvidovre Department of Clinical Physiology and Nuclear Medicine DK-2650 Hvidovre, Kettegårds Allé 30, DK-2650 Hvidovre Aarhus University Hospital: Hepato-gastroenterological Department V Skejby Hospital, Palle Juul-Jensens Blvd., 8200 Aarhus N Department of Nuclear Medicine and PET Skejby Hospital, Palle Juul-Jensens Blvd., 8200 Aarhus N Aalborg University Hospital: Department of Medical Gastroenterology Aalborg