The Biologic Onset of Crohn's Disease: A Screening Study in First Degree Relatives

NCT03291743 | Terminated DMC FDA Device

• 1 other identifier: RTDB-2201
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

Pursuing very early diagnosis is standard of care for several diseases including colon cancer, diabetes and liver disease where an early and aggressive diagnostic and therapeutic approach has been shown to change their natural history. Crohn's disease \[CD\] still lags since commonly at presentation CD has already run a long course, often responding poorly to therapy or requiring surgery. This innovative project proposes a minimally invasive strategy - capsule endoscopy-based screening of first degree relatives \[FDR's\] of CD patients - to develop tools to diagnose CD at or near its biologic onset.

Conditions

Crohn Disease; Genetic Predisposition; IBD

Keywords

Crohn's; Capsule endoscopy; IBD

Outcome Measures

Primary Outcomes (1)

• Prevalence of Crohn's Disease in First Degree Relatives by capsule endoscopy screening

  This study will screen asymptomatic, first-degree relatives of patients with established Crohn's Disease to detect the disease at or near its biologic onset.

  coincident at screening

Secondary Outcomes (1)

• Correlation of capsule endoscopy with ileocolonoscopy; characterization of disease state

  coincident at screening

Study Arms (2)

First Degree Relative

EXPERIMENTAL

A total of 112 high risk first-degree relatives will be enrolled in total. Patients with Crohn's Disease will be given information about the study when in clinic for routine care to share with their first degree relatives (FDR). Screening will be done using capsule endoscopy.

Device: Capsule endoscopy

Healthy Controls

ACTIVE COMPARATOR

This study will also enroll 35 healthy controls who will be age and sex matched to the first degree relative (FDR) population. Enrollment will begin after 20-25 FDR's have passed screening and will continue at this interval until all controls have been enrolled. Controls will be initially screened by colonoscopy. If enrolled they will undergo capsule endoscopy as well

Device: Capsule endoscopy

Interventions

Capsule endoscopy DEVICE

PillCam(TM) CROHN'S CAPSULE

Also known as: PillCam(TM)

First Degree Relative; Healthy Controls

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female who are 18-65 years of age
• FDR: Has a first degree relative (mother, father, offspring, or full sibling) who has been diagnosed with Crohn's Disease Healthy Controls: Normal colonoscopy and histology (if applicable) results, and no family history of inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis)
• Willingness to comply with protocol requirements, timelines, and procedures
• Must be able and willing to provide written consent; medical, surgical, and medication history; current and concomitant medication use; and any other documents deemed relevant by the investigator.
• A negative pregnancy test for all female subjects of childbearing potential at the time of consent. Subject must also agree to follow medically approved birth control measures while enrolled

You may not qualify if:

• Suspected or confirmed diagnosis of inflammatory bowel disease or any other gastrointestinal disease or condition
• Known medical history of clinically significant cardiovascular, hematologic, orthopedic, rheumatologic, muscular, neurologic (e.g. dementia, seizure disorder, traumatic brain injury), endocrine, ophthalmologic, infectious (e.g. human immunodeficiency virus, tuberculosis, hepatitis), immunologic, renal, pulmonary (e.g. COPD), dermatologic, reproductive, or psychiatric disorders, conditions, or diseases that would present unacceptable risk to study subjects, compromise the acquisition or interpretation of study data, or otherwise interfere with the study subject's participation
• A systolic blood pressure reading ≥ 180 mmHg and/or a diastolic blood pressure reading of ≥ 110 mmHg at screening
• An oral temperature reading of 100.5º F or greater
• Meets any of the following criteria:
• Use of systemic non-steroidal anti-inflammatory medication (including low-dose aspirin) within 14 days prior to consent
• History of oral corticosteroid use within 30 days prior to consent
• Use of IV corticosteroids within 14 days prior to consent
• Treatment with IV anti-infectives within 30 days prior to consent
• Treatment with oral anti-infectives within 14 days prior to consent
• Previous or current history of malignancy (including fully excised cutaneous basal cell carcinoma and squamous cell carcinoma)
• History of stem cell or fecal transplant
• History of clinically significant alcoholism or substance abuse in the last 12 months, as defined in the DSM-IV
• Currently has an implanted electrical device (e.g., pacemaker)

Sponsors & Collaborators

• Carilion Clinic: lead

Study Sites (1)

Carilion Clinic

Roanoke, Virginia, 24013, United States

Location

Related Publications (105)

• Cosnes J, Cattan S, Blain A, Beaugerie L, Carbonnel F, Parc R, Gendre JP. Long-term evolution of disease behavior of Crohn's disease. Inflamm Bowel Dis. 2002 Jul;8(4):244-50. doi: 10.1097/00054725-200207000-00002.

  PMID: 12131607 BACKGROUND

• Sorrentino D, Fogel S, Van den Bogaerde J. Surgery for Crohn's disease and anti-TNF agents: the changing scenario. Expert Rev Gastroenterol Hepatol. 2013 Nov;7(8):689-700. doi: 10.1586/17474124.2013.842895.

  PMID: 24161133 BACKGROUND

• Danese S, Fiorino G, Fernandes C, Peyrin-Biroulet L. Catching the therapeutic window of opportunity in early Crohn's disease. Curr Drug Targets. 2014;15(11):1056-63. doi: 10.2174/1389450115666140908125738.

  PMID: 25198784 BACKGROUND

• Gevers D, Kugathasan S, Denson LA, Vazquez-Baeza Y, Van Treuren W, Ren B, Schwager E, Knights D, Song SJ, Yassour M, Morgan XC, Kostic AD, Luo C, Gonzalez A, McDonald D, Haberman Y, Walters T, Baker S, Rosh J, Stephens M, Heyman M, Markowitz J, Baldassano R, Griffiths A, Sylvester F, Mack D, Kim S, Crandall W, Hyams J, Huttenhower C, Knight R, Xavier RJ. The treatment-naive microbiome in new-onset Crohn's disease. Cell Host Microbe. 2014 Mar 12;15(3):382-392. doi: 10.1016/j.chom.2014.02.005.

  PMID: 24629344 BACKGROUND

• Dassopoulos T, Sultan S, Falck-Ytter YT, Inadomi JM, Hanauer SB. American Gastroenterological Association Institute technical review on the use of thiopurines, methotrexate, and anti-TNF-alpha biologic drugs for the induction and maintenance of remission in inflammatory Crohn's disease. Gastroenterology. 2013 Dec;145(6):1464-78.e1-5. doi: 10.1053/j.gastro.2013.10.046. No abstract available.

  PMID: 24267475 BACKGROUND

• Cheifetz AS. Management of active Crohn disease. JAMA. 2013 May 22;309(20):2150-8. doi: 10.1001/jama.2013.4466.

  PMID: 23695484 BACKGROUND

• D'Haens G, Baert F, van Assche G, Caenepeel P, Vergauwe P, Tuynman H, De Vos M, van Deventer S, Stitt L, Donner A, Vermeire S, Van De Mierop FJ, Coche JR, van der Woude J, Ochsenkuhn T, van Bodegraven AA, Van Hootegem PP, Lambrecht GL, Mana F, Rutgeerts P, Feagan BG, Hommes D; Belgian Inflammatory Bowel Disease Research Group; North-Holland Gut Club. Early combined immunosuppression or conventional management in patients with newly diagnosed Crohn's disease: an open randomised trial. Lancet. 2008 Feb 23;371(9613):660-667. doi: 10.1016/S0140-6736(08)60304-9.

  PMID: 18295023 BACKGROUND

• Colombel JF, Sandborn WJ, Rutgeerts P, Enns R, Hanauer SB, Panaccione R, Schreiber S, Byczkowski D, Li J, Kent JD, Pollack PF. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial. Gastroenterology. 2007 Jan;132(1):52-65. doi: 10.1053/j.gastro.2006.11.041. Epub 2006 Nov 29.

  PMID: 17241859 BACKGROUND

• Schreiber S, Colombel JF, Bloomfield R, Nikolaus S, Scholmerich J, Panes J, Sandborn WJ; PRECiSE 2 Study Investigators. Increased response and remission rates in short-duration Crohn's disease with subcutaneous certolizumab pegol: an analysis of PRECiSE 2 randomized maintenance trial data. Am J Gastroenterol. 2010 Jul;105(7):1574-82. doi: 10.1038/ajg.2010.78. Epub 2010 Mar 16.

  PMID: 20234346 BACKGROUND

• Peyrin-Biroulet L, Bigard MA, Malesci A, Danese S. Step-up and top-down approaches to the treatment of Crohn's disease: early may already be too late. Gastroenterology. 2008 Oct;135(4):1420-2. doi: 10.1053/j.gastro.2008.08.017. Epub 2008 Sep 4. No abstract available.

  PMID: 18773901 BACKGROUND

• Rubin DT, Uluscu O, Sederman R. Response to biologic therapy in Crohn's disease is improved with early treatment: an analysis of health claims data. Inflamm Bowel Dis. 2012 Dec;18(12):2225-31. doi: 10.1002/ibd.22925. Epub 2012 Feb 22.

  PMID: 22359399 BACKGROUND

• Schoepfer AM, Dehlavi MA, Fournier N, Safroneeva E, Straumann A, Pittet V, Peyrin-Biroulet L, Michetti P, Rogler G, Vavricka SR; IBD Cohort Study Group. Diagnostic delay in Crohn's disease is associated with a complicated disease course and increased operation rate. Am J Gastroenterol. 2013 Nov;108(11):1744-53; quiz 1754. doi: 10.1038/ajg.2013.248. Epub 2013 Aug 27.

  PMID: 23978953 BACKGROUND

• Feagan BG, Panaccione R, Sandborn WJ, D'Haens GR, Schreiber S, Rutgeerts PJ, Loftus EV Jr, Lomax KG, Yu AP, Wu EQ, Chao J, Mulani P. Effects of adalimumab therapy on incidence of hospitalization and surgery in Crohn's disease: results from the CHARM study. Gastroenterology. 2008 Nov;135(5):1493-9. doi: 10.1053/j.gastro.2008.07.069. Epub 2008 Aug 3.

  PMID: 18848553 BACKGROUND

• Lichtenstein GR, Yan S, Bala M, Blank M, Sands BE. Infliximab maintenance treatment reduces hospitalizations, surgeries, and procedures in fistulizing Crohn's disease. Gastroenterology. 2005 Apr;128(4):862-9. doi: 10.1053/j.gastro.2005.01.048.

  PMID: 15825070 BACKGROUND

• Lichtenstein GR, Yan S, Bala M, Hanauer S. Remission in patients with Crohn's disease is associated with improvement in employment and quality of life and a decrease in hospitalizations and surgeries. Am J Gastroenterol. 2004 Jan;99(1):91-6. doi: 10.1046/j.1572-0241.2003.04010.x.

  PMID: 14687148 BACKGROUND

• Leombruno JP, Nguyen GC, Grootendorst P, Juurlink D, Einarson T. Hospitalization and surgical rates in patients with Crohn's disease treated with infliximab: a matched analysis. Pharmacoepidemiol Drug Saf. 2011 Aug;20(8):838-48. doi: 10.1002/pds.2132. Epub 2011 Jun 17.

  PMID: 21688345 BACKGROUND

• Benevento G, Avellini C, Terrosu G, Geraci M, Lodolo I, Sorrentino D. Diagnosis and assessment of Crohn's disease: the present and the future. Expert Rev Gastroenterol Hepatol. 2010 Dec;4(6):757-66. doi: 10.1586/egh.10.70.

  PMID: 21108595 BACKGROUND

• Vavricka SR, Spigaglia SM, Rogler G, Pittet V, Michetti P, Felley C, Mottet C, Braegger CP, Rogler D, Straumann A, Bauerfeind P, Fried M, Schoepfer AM; Swiss IBD Cohort Study Group. Systematic evaluation of risk factors for diagnostic delay in inflammatory bowel disease. Inflamm Bowel Dis. 2012 Mar;18(3):496-505. doi: 10.1002/ibd.21719. Epub 2011 Apr 20.

  PMID: 21509908 BACKGROUND

• Hovde O, Moum BA. Epidemiology and clinical course of Crohn's disease: results from observational studies. World J Gastroenterol. 2012 Apr 21;18(15):1723-31. doi: 10.3748/wjg.v18.i15.1723.

  PMID: 22553396 BACKGROUND

• Burgmann T, Clara I, Graff L, Walker J, Lix L, Rawsthorne P, McPhail C, Rogala L, Miller N, Bernstein CN. The Manitoba Inflammatory Bowel Disease Cohort Study: prolonged symptoms before diagnosis--how much is irritable bowel syndrome? Clin Gastroenterol Hepatol. 2006 May;4(5):614-20. doi: 10.1016/j.cgh.2006.03.003. Epub 2006 Apr 17.

  PMID: 16630762 BACKGROUND

• Thjodleifsson B, Sigthorsson G, Cariglia N, Reynisdottir I, Gudbjartsson DF, Kristjansson K, Meddings JB, Gudnason V, Wandall JH, Andersen LP, Sherwood R, Kjeld M, Oddsson E, Gudjonsson H, Bjarnason I. Subclinical intestinal inflammation: an inherited abnormality in Crohn's disease relatives? Gastroenterology. 2003 Jun;124(7):1728-37. doi: 10.1016/s0016-5085(03)00383-4.

  PMID: 12806605 BACKGROUND

• Sorrentino D, Avellini C, Geraci M, Dassopoulos T, Zarifi D, Vadala' di Prampero SF, Benevento G. Tissue studies in screened first-degree relatives reveal a distinct Crohn's disease phenotype. Inflamm Bowel Dis. 2014 Jun;20(6):1049-56. doi: 10.1097/MIB.0000000000000051.

  PMID: 24788221 BACKGROUND

• Sorrentino D. Role of biologics and other therapies in stricturing Crohn's disease: what have we learnt so far? Digestion. 2008;77(1):38-47. doi: 10.1159/000117306. Epub 2008 Feb 19.

  PMID: 18285676 BACKGROUND

• Mayberry JF, Ballantyne KC, Hardcastle JD, Mangham C, Pye G. Epidemiological study of asymptomatic inflammatory bowel disease: the identification of cases during a screening programme for colorectal cancer. Gut. 1989 Apr;30(4):481-3. doi: 10.1136/gut.30.4.481.

  PMID: 2785474 BACKGROUND

• Sorrentino D. Preclinical and Undiagnosed Crohn's Disease: The Submerged Iceberg. Inflamm Bowel Dis. 2016 Feb;22(2):476-86. doi: 10.1097/MIB.0000000000000612.

  PMID: 26752471 BACKGROUND

• Harris R, Sawaya GF, Moyer VA, Calonge N. Reconsidering the criteria for evaluating proposed screening programs: reflections from 4 current and former members of the U.S. Preventive services task force. Epidemiol Rev. 2011;33:20-35. doi: 10.1093/epirev/mxr005. Epub 2011 Jun 10.

  PMID: 21666224 BACKGROUND

• Geboes K. The strategy for biopsies of the terminal ileum should be evidence based. Am J Gastroenterol. 2007 May;102(5):1090-2. doi: 10.1111/j.1572-0241.2007.01190.x.

  PMID: 17489785 BACKGROUND

• Fries W, Renda MC, Lo Presti MA, Raso A, Orlando A, Oliva L, Giofre MR, Maggio A, Mattaliano A, Macaluso A, Cottone M. Intestinal permeability and genetic determinants in patients, first-degree relatives, and controls in a high-incidence area of Crohn's disease in Southern Italy. Am J Gastroenterol. 2005 Dec;100(12):2730-6. doi: 10.1111/j.1572-0241.2005.00325.x.

  PMID: 16393227 BACKGROUND

• Orholm M, Fonager K, Sorensen HT. Risk of ulcerative colitis and Crohn's disease among offspring of patients with chronic inflammatory bowel disease. Am J Gastroenterol. 1999 Nov;94(11):3236-8. doi: 10.1111/j.1572-0241.1999.01526.x.

  PMID: 10566721 BACKGROUND

• Ahmad T, Satsangi J, McGovern D, Bunce M, Jewell DP. Review article: the genetics of inflammatory bowel disease. Aliment Pharmacol Ther. 2001 Jun;15(6):731-48. doi: 10.1046/j.1365-2036.2001.00981.x.

  PMID: 11380312 BACKGROUND

• Pham M, Leach ST, Lemberg DA, Day AS. Subclinical intestinal inflammation in siblings of children with Crohn's disease. Dig Dis Sci. 2010 Dec;55(12):3502-7. doi: 10.1007/s10620-010-1434-8. Epub 2010 Oct 8.

  PMID: 20931283 BACKGROUND

• Montalto M, Curigliano V, Santoro L, Armuzzi A, Cammarota G, Covino M, Mentella MC, Ancarani F, Manna R, Gasbarrini A, Gasbarrini G. Fecal calprotectin in first-degree relatives of patients with ulcerative colitis. Am J Gastroenterol. 2007 Jan;102(1):132-6. doi: 10.1111/j.1572-0241.2006.00884.x. Epub 2006 Nov 13.

  PMID: 17100982 BACKGROUND

• Tamboli CP, Richard F, Colombel JF. Fecal calprotectin in Crohn's disease: new family ties. Gastroenterology. 2003 Jun;124(7):1972-4. doi: 10.1016/s0016-5085(03)00552-3. No abstract available.

  PMID: 12806631 BACKGROUND

• Soderholm JD, Olaison G, Lindberg E, Hannestad U, Vindels A, Tysk C, Jarnerot G, Sjodahl R. Different intestinal permeability patterns in relatives and spouses of patients with Crohn's disease: an inherited defect in mucosal defence? Gut. 1999 Jan;44(1):96-100. doi: 10.1136/gut.44.1.96.

  PMID: 9862833 BACKGROUND

• Sendid B, Quinton JF, Charrier G, Goulet O, Cortot A, Grandbastien B, Poulain D, Colombel JF. Anti-Saccharomyces cerevisiae mannan antibodies in familial Crohn's disease. Am J Gastroenterol. 1998 Aug;93(8):1306-10. doi: 10.1111/j.1572-0241.1998.00415.x.

  PMID: 9707056 BACKGROUND

• Ananthakrishnan AN. Environmental risk factors for inflammatory bowel diseases: a review. Dig Dis Sci. 2015 Feb;60(2):290-8. doi: 10.1007/s10620-014-3350-9. Epub 2014 Sep 10.

  PMID: 25204669 BACKGROUND

• Peeters M, Geypens B, Claus D, Nevens H, Ghoos Y, Verbeke G, Baert F, Vermeire S, Vlietinck R, Rutgeerts P. Clustering of increased small intestinal permeability in families with Crohn's disease. Gastroenterology. 1997 Sep;113(3):802-7. doi: 10.1016/s0016-5085(97)70174-4.

  PMID: 9287971 BACKGROUND

• Israeli E, Grotto I, Gilburd B, Balicer RD, Goldin E, Wiik A, Shoenfeld Y. Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease. Gut. 2005 Sep;54(9):1232-6. doi: 10.1136/gut.2004.060228.

  PMID: 16099791 BACKGROUND

• Efrat B, Iris G, Wang H, Eitan S, Yona K. A subgroup of first-degree relatives of Crohn's disease patients shows a profile of inflammatory markers in the blood which is more typical of Crohn's disease patients than of normal individuals. Mediators Inflamm. 2006;2006(2):74785. doi: 10.1155/MI/2006/74785.

  PMID: 16883067 BACKGROUND

• Annese V, Andreoli A, Andriulli A, Dinca R, Gionchetti P, Latiano A, Lombardi G, Piepoli A, Poulain D, Sendid B, Colombel JF. Familial expression of anti-Saccharomyces cerevisiae Mannan antibodies in Crohn's disease and ulcerative colitis: a GISC study. Am J Gastroenterol. 2001 Aug;96(8):2407-12. doi: 10.1111/j.1572-0241.2001.04043.x.

  PMID: 11513182 BACKGROUND

• Elmgreen J, Both H, Binder V. Familial occurrence of complement dysfunction in Crohn's disease: correlation with intestinal symptoms and hypercatabolism of complement. Gut. 1985 Feb;26(2):151-7. doi: 10.1136/gut.26.2.151.

  PMID: 3967833 BACKGROUND

• Joossens M, Huys G, Cnockaert M, De Preter V, Verbeke K, Rutgeerts P, Vandamme P, Vermeire S. Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives. Gut. 2011 May;60(5):631-7. doi: 10.1136/gut.2010.223263. Epub 2011 Jan 5.

  PMID: 21209126 BACKGROUND

• Mei L, Targan SR, Landers CJ, Dutridge D, Ippoliti A, Vasiliauskas EA, Papadakis KA, Fleshner PR, Rotter JI, Yang H. Familial expression of anti-Escherichia coli outer membrane porin C in relatives of patients with Crohn's disease. Gastroenterology. 2006 Apr;130(4):1078-85. doi: 10.1053/j.gastro.2006.02.013.

  PMID: 16618402 BACKGROUND

• Devlin SM, Yang H, Ippoliti A, Taylor KD, Landers CJ, Su X, Abreu MT, Papadakis KA, Vasiliauskas EA, Melmed GY, Fleshner PR, Mei L, Rotter JI, Targan SR. NOD2 variants and antibody response to microbial antigens in Crohn's disease patients and their unaffected relatives. Gastroenterology. 2007 Feb;132(2):576-86. doi: 10.1053/j.gastro.2006.11.013. Epub 2006 Nov 10.

  PMID: 17258734 BACKGROUND

• Folwaczny C, Noehl N, Endres SP, Heldwein W, Loeschke K, Fricke H. Antinuclear autoantibodies in patients with inflammatory bowel disease. High prevalence in first-degree relatives. Dig Dis Sci. 1997 Aug;42(8):1593-7. doi: 10.1023/a:1018832608899.

  PMID: 9286222 BACKGROUND

• Folwaczny C, Noehl N, Tschop K, Endres SP, Heldwein W, Loeschke K, Fricke H. Goblet cell autoantibodies in patients with inflammatory bowel disease and their first-degree relatives. Gastroenterology. 1997 Jul;113(1):101-6. doi: 10.1016/s0016-5085(97)70085-4.

  PMID: 9207267 BACKGROUND

• Bjarnason I, Helgason KO, Geirsson AJ, Sigthorsson G, Reynisdottir I, Gudbjartsson D, Einarsdottir AS, Sherwood R, Kristjansson K, Kjartansson O, Thjodleifsson B. Subclinical intestinal inflammation and sacroiliac changes in relatives of patients with ankylosing spondylitis. Gastroenterology. 2003 Dec;125(6):1598-605. doi: 10.1053/j.gastro.2003.08.035.

  PMID: 14724811 BACKGROUND

• Dorn SD, Abad JF, Panagopoulos G, Korelitz BI. Clinical characteristics of familial versus sporadic Crohn's disease using the Vienna Classification. Inflamm Bowel Dis. 2004 May;10(3):201-6. doi: 10.1097/00054725-200405000-00004.

  PMID: 15290912 BACKGROUND

• D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998 Feb;114(2):262-7. doi: 10.1016/s0016-5085(98)70476-7.

  PMID: 9453485 BACKGROUND

• Sandborn WJ, Feagan BG, Hanauer SB, Lochs H, Lofberg R, Modigliani R, Present DH, Rutgeerts P, Scholmerich J, Stange EF, Sutherland LR. A review of activity indices and efficacy endpoints for clinical trials of medical therapy in adults with Crohn's disease. Gastroenterology. 2002 Feb;122(2):512-30. doi: 10.1053/gast.2002.31072. No abstract available.

  PMID: 11832465 BACKGROUND

• Zwas FR, Cirillo NW, el-Serag HB, Eisen RN. Colonic mucosal abnormalities associated with oral sodium phosphate solution. Gastrointest Endosc. 1996 May;43(5):463-6. doi: 10.1016/s0016-5107(96)70286-9.

  PMID: 8726758 BACKGROUND

• Zhulina Y, Hahn-Stromberg V, Shamikh A, Peterson CG, Gustavsson A, Nyhlin N, Wickbom A, Bohr J, Bodin L, Tysk C, Carlson M, Halfvarson J. Subclinical inflammation with increased neutrophil activity in healthy twin siblings reflect environmental influence in the pathogenesis of inflammatory bowel disease. Inflamm Bowel Dis. 2013 Jul;19(8):1725-31. doi: 10.1097/MIB.0b013e318281f2d3.

  PMID: 23669399 BACKGROUND

• Krauss E, Agaimy A, Neumann H, Schulz U, Kessler H, Hartmann A, Neurath MF, Raithel M, Mudter J. Characterization of lymphoid follicles with red ring signs as first manifestation of early Crohn's disease by conventional histopathology and confocal laser endomicroscopy. Int J Clin Exp Pathol. 2012;5(5):411-21. Epub 2012 May 23.

  PMID: 22808293 BACKGROUND

• Fujimura Y, Kamoi R, Iida M. Pathogenesis of aphthoid ulcers in Crohn's disease: correlative findings by magnifying colonoscopy, electron microscopy, and immunohistochemistry. Gut. 1996 May;38(5):724-32. doi: 10.1136/gut.38.5.724.

  PMID: 8707119 BACKGROUND

• Gullberg E, Soderholm JD. Peyer's patches and M cells as potential sites of the inflammatory onset in Crohn's disease. Ann N Y Acad Sci. 2006 Aug;1072:218-32. doi: 10.1196/annals.1326.028.

  PMID: 17057202 BACKGROUND

• Morson BC. The early histological lesion of Crohn's disease. Proc R Soc Med. 1972 Jan;65(1):71-2. doi: 10.1177/003591577206500129. No abstract available.

  PMID: 5015484 BACKGROUND

• Maloy KJ, Powrie F. Intestinal homeostasis and its breakdown in inflammatory bowel disease. Nature. 2011 Jun 15;474(7351):298-306. doi: 10.1038/nature10208.

  PMID: 21677746 BACKGROUND

• Zorzi F, Monteleone I, Sarra M, Calabrese E, Marafini I, Cretella M, Sedda S, Biancone L, Pallone F, Monteleone G. Distinct profiles of effector cytokines mark the different phases of Crohn's disease. PLoS One. 2013;8(1):e54562. doi: 10.1371/journal.pone.0054562. Epub 2013 Jan 17.

  PMID: 23349929 BACKGROUND

• Hedin CR, McCarthy NE, Louis P, Farquharson FM, McCartney S, Taylor K, Prescott NJ, Murrells T, Stagg AJ, Whelan K, Lindsay JO. Altered intestinal microbiota and blood T cell phenotype are shared by patients with Crohn's disease and their unaffected siblings. Gut. 2014 Oct;63(10):1578-86. doi: 10.1136/gutjnl-2013-306226. Epub 2014 Jan 7.

  PMID: 24398881 BACKGROUND

• Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014 May;146(6):1489-99. doi: 10.1053/j.gastro.2014.02.009. Epub 2014 Feb 19.

  PMID: 24560869 BACKGROUND

• Sartor RB. Genetics and environmental interactions shape the intestinal microbiome to promote inflammatory bowel disease versus mucosal homeostasis. Gastroenterology. 2010 Dec;139(6):1816-9. doi: 10.1053/j.gastro.2010.10.036. Epub 2010 Oct 26. No abstract available.

  PMID: 21029802 BACKGROUND

• Mukherjee PK, Sendid B, Hoarau G, Colombel JF, Poulain D, Ghannoum MA. Mycobiota in gastrointestinal diseases. Nat Rev Gastroenterol Hepatol. 2015 Feb;12(2):77-87. doi: 10.1038/nrgastro.2014.188. Epub 2014 Nov 11.

  PMID: 25385227 BACKGROUND

• Moyes DL, Naglik JR. The mycobiome: influencing IBD severity. Cell Host Microbe. 2012 Jun 14;11(6):551-2. doi: 10.1016/j.chom.2012.05.009.

  PMID: 22704612 BACKGROUND

• Iliev ID, Funari VA, Taylor KD, Nguyen Q, Reyes CN, Strom SP, Brown J, Becker CA, Fleshner PR, Dubinsky M, Rotter JI, Wang HL, McGovern DP, Brown GD, Underhill DM. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science. 2012 Jun 8;336(6086):1314-7. doi: 10.1126/science.1221789. Epub 2012 Jun 6.

  PMID: 22674328 BACKGROUND

• Standaert-Vitse A, Sendid B, Joossens M, Francois N, Vandewalle-El Khoury P, Branche J, Van Kruiningen H, Jouault T, Rutgeerts P, Gower-Rousseau C, Libersa C, Neut C, Broly F, Chamaillard M, Vermeire S, Poulain D, Colombel JF. Candida albicans colonization and ASCA in familial Crohn's disease. Am J Gastroenterol. 2009 Jul;104(7):1745-53. doi: 10.1038/ajg.2009.225. Epub 2009 May 26.

  PMID: 19471251 BACKGROUND

• Hedin CR, Stagg AJ, Whelan K, Lindsay JO. Family studies in Crohn's disease: new horizons in understanding disease pathogenesis, risk and prevention. Gut. 2012 Feb;61(2):311-8. doi: 10.1136/gut.2011.238568. Epub 2011 May 11.

  PMID: 21561876 BACKGROUND

• Sorrentino D, Avellini C, Geraci M, Vadala S. Pre-clinical Crohn's disease: diagnosis, treatment and six year follow-up. J Crohns Colitis. 2014 Jul;8(7):702-7. doi: 10.1016/j.crohns.2013.12.008. Epub 2014 Jan 8.

  PMID: 24411923 BACKGROUND

• Barnes MJ, Powrie F. Regulatory T cells reinforce intestinal homeostasis. Immunity. 2009 Sep 18;31(3):401-11. doi: 10.1016/j.immuni.2009.08.011.

  PMID: 19766083 BACKGROUND

• Fantini MC, Rizzo A, Fina D, Caruso R, Sarra M, Stolfi C, Becker C, Macdonald TT, Pallone F, Neurath MF, Monteleone G. Smad7 controls resistance of colitogenic T cells to regulatory T cell-mediated suppression. Gastroenterology. 2009 Apr;136(4):1308-16, e1-3. doi: 10.1053/j.gastro.2008.12.053. Epub 2008 Dec 27.

  PMID: 19192480 BACKGROUND

• Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases. Gastroenterology. 2011 May;140(6):1756-1767. doi: 10.1053/j.gastro.2011.02.016.

  PMID: 21530742 BACKGROUND

• Papp M, Lakatos PL. Serological studies in inflammatory bowel disease: how important are they? Curr Opin Gastroenterol. 2014 Jul;30(4):359-64. doi: 10.1097/MOG.0000000000000076.

  PMID: 24811052 BACKGROUND

• van Schaik FD, Oldenburg B, Hart AR, Siersema PD, Lindgren S, Grip O, Teucher B, Kaaks R, Bergmann MM, Boeing H, Carbonnel F, Jantchou P, Boutron-Ruault MC, Tjonneland A, Olsen A, Crowe FL, Peeters PH, van Oijen MG, Bueno-de-Mesquita HB. Serological markers predict inflammatory bowel disease years before the diagnosis. Gut. 2013 May;62(5):683-8. doi: 10.1136/gutjnl-2012-302717. Epub 2012 Jul 26.

  PMID: 22842615 BACKGROUND

• Lonnkvist MH, Theodorsson E, Holst M, Ljung T, Hellstrom PM. Blood chemistry markers for evaluation of inflammatory activity in Crohn's disease during infliximab therapy. Scand J Gastroenterol. 2011 Apr;46(4):420-7. doi: 10.3109/00365521.2010.539253. Epub 2010 Nov 30.

  PMID: 21114432 BACKGROUND

• Kopylov U, Rosenfeld G, Bressler B, Seidman E. Clinical utility of fecal biomarkers for the diagnosis and management of inflammatory bowel disease. Inflamm Bowel Dis. 2014 Apr;20(4):742-56. doi: 10.1097/01.MIB.0000442681.85545.31.

  PMID: 24562174 BACKGROUND

• Sorrentino D, Terrosu G, Paviotti A, Geraci M, Avellini C, Zoli G, Fries W, Danese S, Occhipinti P, Croatto T, Zarifi D. Early diagnosis and treatment of postoperative endoscopic recurrence of Crohn's disease: partial benefit by infliximab--a pilot study. Dig Dis Sci. 2012 May;57(5):1341-8. doi: 10.1007/s10620-011-2025-z. Epub 2012 Jan 18.

  PMID: 22252267 BACKGROUND

• Sorrentino D, Paviotti A, Terrosu G, Avellini C, Geraci M, Zarifi D. Low-dose maintenance therapy with infliximab prevents postsurgical recurrence of Crohn's disease. Clin Gastroenterol Hepatol. 2010 Jul;8(7):591-9.e1; quiz e78-9. doi: 10.1016/j.cgh.2010.01.016. Epub 2010 Feb 4.

  PMID: 20139033 BACKGROUND

• Hyams J, Crandall W, Kugathasan S, Griffiths A, Olson A, Johanns J, Liu G, Travers S, Heuschkel R, Markowitz J, Cohen S, Winter H, Veereman-Wauters G, Ferry G, Baldassano R; REACH Study Group. Induction and maintenance infliximab therapy for the treatment of moderate-to-severe Crohn's disease in children. Gastroenterology. 2007 Mar;132(3):863-73; quiz 1165-6. doi: 10.1053/j.gastro.2006.12.003. Epub 2006 Dec 3.

  PMID: 17324398 BACKGROUND

• Goutorbe F, Goutte M, Minet-Quinard R, Boucher AL, Pereira B, Bommelaer G, Buisson A. Endoscopic Factors Influencing Fecal Calprotectin Value in Crohn's Disease. J Crohns Colitis. 2015 Dec;9(12):1113-9. doi: 10.1093/ecco-jcc/jjv150. Epub 2015 Sep 7.

  PMID: 26351383 BACKGROUND

• Sipponen T, Karkkainen P, Savilahti E, Kolho KL, Nuutinen H, Turunen U, Farkkila M. Correlation of faecal calprotectin and lactoferrin with an endoscopic score for Crohn's disease and histological findings. Aliment Pharmacol Ther. 2008 Nov 15;28(10):1221-9. doi: 10.1111/j.1365-2036.2008.03835.x. Epub 2008 Aug 26.

  PMID: 18752630 BACKGROUND

• Soubieres AA, Poullis A. Emerging role of novel biomarkers in the diagnosis of inflammatory bowel disease. World J Gastrointest Pharmacol Ther. 2016 Feb 6;7(1):41-50. doi: 10.4292/wjgpt.v7.i1.41.

  PMID: 26855811 BACKGROUND

• Albert JG, Kotsch J, Kostler W, Behl S, Kaltz B, Bokemeyer B, Dollinger MM, Haerting J, Fleig WE. Course of Crohn's disease prior to establishment of the diagnosis. Z Gastroenterol. 2008 Feb;46(2):187-92. doi: 10.1055/s-2007-963524.

  PMID: 18253897 BACKGROUND

• Li Y, Ren J, Wang G, Gu G, Wu X, Ren H, Hong Z, Hu D, Wu Q, Li G, Liu S, Anjum N, Li J. Diagnostic delay in Crohn's disease is associated with increased rate of abdominal surgery: A retrospective study in Chinese patients. Dig Liver Dis. 2015 Jul;47(7):544-8. doi: 10.1016/j.dld.2015.03.004. Epub 2015 Mar 14.

  PMID: 25840874 BACKGROUND

• Pellino G, Sciaudone G, Selvaggi F, Riegler G. Delayed diagnosis is influenced by the clinical pattern of Crohn's disease and affects treatment outcomes and quality of life in the long term: a cross-sectional study of 361 patients in Southern Italy. Eur J Gastroenterol Hepatol. 2015 Feb;27(2):175-81. doi: 10.1097/MEG.0000000000000244.

  PMID: 25461228 BACKGROUND

• Louis E, Collard A, Oger AF, Degroote E, Aboul Nasr El Yafi FA, Belaiche J. Behaviour of Crohn's disease according to the Vienna classification: changing pattern over the course of the disease. Gut. 2001 Dec;49(6):777-82. doi: 10.1136/gut.49.6.777.

  PMID: 11709511 BACKGROUND

• Solberg IC, Vatn MH, Hoie O, Stray N, Sauar J, Jahnsen J, Moum B, Lygren I; IBSEN Study Group. Clinical course in Crohn's disease: results of a Norwegian population-based ten-year follow-up study. Clin Gastroenterol Hepatol. 2007 Dec;5(12):1430-8. doi: 10.1016/j.cgh.2007.09.002.

  PMID: 18054751 BACKGROUND

• Kelly JK, Sutherland LR. The chronological sequence in the pathology of Crohn's disease. J Clin Gastroenterol. 1988 Feb;10(1):28-33. doi: 10.1097/00004836-198802000-00008.

  PMID: 3356881 BACKGROUND

• Greenstein AJ, Lachman P, Sachar DB, Springhorn J, Heimann T, Janowitz HD, Aufses AH Jr. Perforating and non-perforating indications for repeated operations in Crohn's disease: evidence for two clinical forms. Gut. 1988 May;29(5):588-92. doi: 10.1136/gut.29.5.588.

  PMID: 3396946 BACKGROUND

• Limketkai BN, Bayless TM. Editorial: Can stenosis in ileal Crohn's disease be prevented by current therapy? Am J Gastroenterol. 2013 Nov;108(11):1755-6. doi: 10.1038/ajg.2013.301.

  PMID: 24192948 BACKGROUND

• Jacene HA, Ginsburg P, Kwon J, Nguyen GC, Montgomery EA, Bayless TM, Wahl RL. Prediction of the need for surgical intervention in obstructive Crohn's disease by 18F-FDG PET/CT. J Nucl Med. 2009 Nov;50(11):1751-9. doi: 10.2967/jnumed.109.065466. Epub 2009 Oct 16.

  PMID: 19837758 BACKGROUND

• Cummings SA, Rubin DT. The complexity and challenges of genetic counseling and testing for inflammatory bowel disease. J Genet Couns. 2006 Dec;15(6):465-76. doi: 10.1007/s10897-006-9057-0.

  PMID: 17106630 BACKGROUND

• Liu JZ, Anderson CA. Genetic studies of Crohn's disease: past, present and future. Best Pract Res Clin Gastroenterol. 2014 Jun;28(3):373-86. doi: 10.1016/j.bpg.2014.04.009. Epub 2014 May 6.

  PMID: 24913378 BACKGROUND

• Leighton JA, Gralnek IM, Cohen SA, Toth E, Cave DR, Wolf DC, Mullin GE, Ketover SR, Legnani PE, Seidman EG, Crowell MD, Bergwerk AJ, Peled R, Eliakim R. Capsule endoscopy is superior to small-bowel follow-through and equivalent to ileocolonoscopy in suspected Crohn's disease. Clin Gastroenterol Hepatol. 2014 Apr;12(4):609-15. doi: 10.1016/j.cgh.2013.09.028. Epub 2013 Sep 27.

  PMID: 24075891 BACKGROUND

• Triester SL, Leighton JA, Leontiadis GI, Gurudu SR, Fleischer DE, Hara AK, Heigh RI, Shiff AD, Sharma VK. A meta-analysis of the yield of capsule endoscopy compared to other diagnostic modalities in patients with non-stricturing small bowel Crohn's disease. Am J Gastroenterol. 2006 May;101(5):954-64. doi: 10.1111/j.1572-0241.2006.00506.x.

  PMID: 16696781 BACKGROUND

• Jensen MD, Nathan T, Rafaelsen SR, Kjeldsen J. Diagnostic accuracy of capsule endoscopy for small bowel Crohn's disease is superior to that of MR enterography or CT enterography. Clin Gastroenterol Hepatol. 2011 Feb;9(2):124-9. doi: 10.1016/j.cgh.2010.10.019. Epub 2010 Nov 5.

  PMID: 21056692 BACKGROUND

• Sipponen T, Haapamaki J, Savilahti E, Alfthan H, Hamalainen E, Rautiainen H, Koskenpato J, Nuutinen H, Farkkila M. Fecal calprotectin and S100A12 have low utility in prediction of small bowel Crohn's disease detected by wireless capsule endoscopy. Scand J Gastroenterol. 2012 Jul;47(7):778-84. doi: 10.3109/00365521.2012.677953. Epub 2012 Apr 23.

  PMID: 22519419 BACKGROUND

• Maiden L, Thjodleifsson B, Theodors A, Gonzalez J, Bjarnason I. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy. Gastroenterology. 2005 May;128(5):1172-8. doi: 10.1053/j.gastro.2005.03.020.

  PMID: 15887101 BACKGROUND

• Gralnek IM, Defranchis R, Seidman E, Leighton JA, Legnani P, Lewis BS. Development of a capsule endoscopy scoring index for small bowel mucosal inflammatory change. Aliment Pharmacol Ther. 2008 Jan 15;27(2):146-54. doi: 10.1111/j.1365-2036.2007.03556.x. Epub 2007 Oct 23.

  PMID: 17956598 BACKGROUND

• Biancone L, Calabrese E, Petruzziello C, Capanna A, Zorzi F, Onali S, Condino G, Lolli E, Ciccacci C, Borgiani P, Pallone F. A family study of asymptomatic small bowel Crohn's disease. Dig Liver Dis. 2014 Mar;46(3):276-8. doi: 10.1016/j.dld.2013.11.003. Epub 2013 Dec 17.

  PMID: 24360029 BACKGROUND

• Sands BE. From symptom to diagnosis: clinical distinctions among various forms of intestinal inflammation. Gastroenterology. 2004 May;126(6):1518-32. doi: 10.1053/j.gastro.2004.02.072. No abstract available.

  PMID: 15168364 BACKGROUND

• Bennett RA, Rubin PH, Present DH. Frequency of inflammatory bowel disease in offspring of couples both presenting with inflammatory bowel disease. Gastroenterology. 1991 Jun;100(6):1638-43. doi: 10.1016/0016-5085(91)90663-6.

  PMID: 2019369 BACKGROUND

• Noble CL, Arnott ID. What is the risk that a child will develop inflammatory bowel disease if 1 or both parents have IBD? Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S22-3. doi: 10.1002/ibd.20575. No abstract available.

  PMID: 18816708 BACKGROUND

• Russell RK, Satsangi J. Does IBD run in families? Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S20-1. doi: 10.1002/ibd.20573. No abstract available.

  PMID: 18816757 BACKGROUND

• Probert CS, Brown M. Are there any ethnic groups that are more likely to develop IBD? Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S24-5. doi: 10.1002/ibd.20601. No abstract available.

  PMID: 18816723 BACKGROUND

• Yan B, Panaccione R, Sutherland L. I am Jewish: what is my risk of developing Crohn's disease? Inflamm Bowel Dis. 2008 Oct;14 Suppl 2:S26-7. doi: 10.1002/ibd.20691. No abstract available.

  PMID: 18816782 BACKGROUND

• Shrout PE, Fleiss JL. Intraclass correlations: uses in assessing rater reliability. Psychol Bull. 1979 Mar;86(2):420-8. doi: 10.1037//0033-2909.86.2.420.

  PMID: 18839484 BACKGROUND

MeSH Terms

Conditions

Crohn Disease; Genetic Predisposition to Disease

Interventions

Capsule Endoscopy

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases; Disease Susceptibility; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Endoscopy; Diagnostic Techniques, Surgical; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Dario R Sorrentino, MD, FRACP

  Carilion Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2017
• First Posted: September 25, 2017
• Study Start: February 10, 2017
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: December 13, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)