Evaluating Gut Imaging and Stool Biomarkers in Patients With Scleroderma-associated Gastrointestinal Disease
NCT ID: NCT04630782
Last Updated: 2020-11-24
Study Results
Results pending
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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Recruitment Status
UNKNOWN
Total Enrollment
70 participants
Study Classification
OBSERVATIONAL
Study Start Date
2020-04-09
Study Completion Date
2023-01-31
Brief Summary
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Systemic sclerosis (SSc) is characterized by autoimmunity and vasculopathy resulting in fibrosis of the skin and internal organs including the Gastrointestinal (GI) tract. Key unmet clinical needs are the availability of non-invasive biomarkers for early diagnosis of SSc-GI, further characterization of different stages of SSc-GI and SSc-GI treatment response. The investigators propose combining MRI FDG-PET with MRI T1-MOLLI mapping, which has been applied to cardiac imaging to quantify histologically correlated cardiac fibrosis. T1-MOLLI enables detection and quantification of diffuse fibrosis without the need for contrast.
Aim 1: FDG-PET-MRI imaging (primary biomarker) and stool markers (secondary biomarker) will be compared between patients with VEDOSS/early SSc and those with late SSc not on immunosuppressive treatment.
Aim 2: Evaluation of change in biomarker levels from pre-treatment baseline to 6 months (primary end-point) and 12-months (secondary end-point) following MMF treatment, in early SSc patients
Using precision medicine approach in diagnosis and treatment evaluation, the investigators anticipate that this study will contribute significantly to advance management strategies for, and improve outcomes of SSc-GI disease.
Aim 1: FDG-PET-MRI imaging (primary biomarker) and stool markers (secondary biomarker) will be compared between patients with VEDOSS/early SSc and those with late SSc not on immunosuppressive treatment.
Aim 2: Evaluation of change in biomarker levels from pre-treatment baseline to 6 months (primary end-point) and 12-months (secondary end-point) following MMF treatment, in early SSc patients
Using precision medicine approach in diagnosis and treatment evaluation, the investigators anticipate that this study will contribute significantly to advance management strategies for, and improve outcomes of SSc-GI disease.
Detailed Description
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1. Aim 1 Determine if FDG-PET-MRI imaging biomarkers differentiate patients with VEDOSS/ early SSc (predominantly inflammatory) from those with late SSc (predominantly fibrosis). Stool markers will be used as secondary biomarkers supporting inflammation.
Study design: cross-sectional; The investigators will compare biomarkers between patients with VEDOSS/early SSc and those with late SSc not on immunosuppressive treatment.
2. Aim 2 Evaluate FDG-PET-MRI imaging biomarker change over a 6- and 12-month treatment period with mycophenolate mofetil (MMF) in patients with early SSc. Stool markers will be used as secondary biomarkers supporting inflammation.
Study design: longitudinal; In early SSc patients, the investigators will determine change in biomarker levels from pre-treatment baseline to 6 months (primary end-point) and 12-months (secondary end-point) following MMF treatment.
3. Exploratory Aim: In patients with VEDOSS/early SSc not on immunosuppressive treatment, the investigators will characterize imaging and stool biomarker changes over one year.
Study design: cross-sectional; The investigators will compare biomarkers between patients with VEDOSS/early SSc and those with late SSc not on immunosuppressive treatment.
2. Aim 2 Evaluate FDG-PET-MRI imaging biomarker change over a 6- and 12-month treatment period with mycophenolate mofetil (MMF) in patients with early SSc. Stool markers will be used as secondary biomarkers supporting inflammation.
Study design: longitudinal; In early SSc patients, the investigators will determine change in biomarker levels from pre-treatment baseline to 6 months (primary end-point) and 12-months (secondary end-point) following MMF treatment.
3. Exploratory Aim: In patients with VEDOSS/early SSc not on immunosuppressive treatment, the investigators will characterize imaging and stool biomarker changes over one year.
Conditions
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Systemic Sclerosis
Scleroderma
Keywords
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Systemic Sclerosis
Imaging, Diagnostic
MRI Scans
PET-MRI Scan
Study Design
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Observational Model Type
COHORT
Study Time Perspective
PROSPECTIVE
Study Groups
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Aim 1
The investigators will compare PET-MRI imaging and stool biomarkers between patients with VEDOSS/early SSc (n=40) and those with late SSc (n=20) not on immunosuppressive treatment.
Participants will undergo a PET-MRI scan once at baseline.
PET-MRI scan
Intervention Type
DIAGNOSTIC_TEST
Participants will be scanned centrally at Clinical Imaging Research Centre (CIRC, Singapore), on a Biograph mMR PET-MR scanner. Combined FDG-PET-MRI scan is critical for co-registration of peristaltic bowel for optimal image quality. The oesophagus to anorectum will be imaged. The PET-MRI scan starts 60 minutes post-FDG injection of 6mCi and immediately after injecting 10mg hyoscine butylbromide to reduce peristalsis. MRI sequences are non-contrast.
Aim 2
In early SSc patients (n=35), the investigators will determine change in biomarker levels from pre-treatment baseline to 6 months (primary end-point) and 12-months (secondary end-point) following MMF treatment.
Participants will undergo PET-MRI scans at baseline, 6-month and 12-month.
PET-MRI scan
Intervention Type
DIAGNOSTIC_TEST
Participants will be scanned centrally at Clinical Imaging Research Centre (CIRC, Singapore), on a Biograph mMR PET-MR scanner. Combined FDG-PET-MRI scan is critical for co-registration of peristaltic bowel for optimal image quality. The oesophagus to anorectum will be imaged. The PET-MRI scan starts 60 minutes post-FDG injection of 6mCi and immediately after injecting 10mg hyoscine butylbromide to reduce peristalsis. MRI sequences are non-contrast.
Exploratory aim
In patients with VEDOSS/early SSc (n=15) not on immunosuppressive treatment, the investigators will characterize imaging and stool biomarker changes over one year.
Participants will undergo PET-MRI scans at baseline and 12-month.
PET-MRI scan
Intervention Type
DIAGNOSTIC_TEST
Participants will be scanned centrally at Clinical Imaging Research Centre (CIRC, Singapore), on a Biograph mMR PET-MR scanner. Combined FDG-PET-MRI scan is critical for co-registration of peristaltic bowel for optimal image quality. The oesophagus to anorectum will be imaged. The PET-MRI scan starts 60 minutes post-FDG injection of 6mCi and immediately after injecting 10mg hyoscine butylbromide to reduce peristalsis. MRI sequences are non-contrast.
Interventions
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PET-MRI scan
Participants will be scanned centrally at Clinical Imaging Research Centre (CIRC, Singapore), on a Biograph mMR PET-MR scanner. Combined FDG-PET-MRI scan is critical for co-registration of peristaltic bowel for optimal image quality. The oesophagus to anorectum will be imaged. The PET-MRI scan starts 60 minutes post-FDG injection of 6mCi and immediately after injecting 10mg hyoscine butylbromide to reduce peristalsis. MRI sequences are non-contrast.
Intervention Type
DIAGNOSTIC_TEST
Eligibility Criteria
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Inclusion Criteria
(i) ≥ 21 years old (ii) SSc fulfilling the American College of Rheumatology/European League Against Rheumatism (EULAR) 2013 criteria or VEDOSS fulfilling proposed criteria by EULAR
Aim 1 subject stratification:
(i) VEDOSS/ early SSc (≤3 years) or late SSc (\> 5 years), with disease duration defined from onset of first non-Raynaud's symptom (ii) Not on any immunosuppressive treatment or prednisolone \>10 mg /day 8 weeks before recruitment
Aim 2 subject stratification:
(i) early SSc (≤3 years) and (ii) starting on immunosuppressive treatment either
1. MMF + Prednisolone or
2. Other immunosuppressive treatment in combination with MMF + Prednisolone
Exploratory aim subject stratification:
(i) VEDOSS or early SSc (≤3 years) with disease duration defined from onset of first non-Raynaud's symptom (ii) Not on any immunosuppressive treatment or prednisolone \>10 mg /day 8 weeks before recruitment
Aim 1 subject stratification:
(i) VEDOSS/ early SSc (≤3 years) or late SSc (\> 5 years), with disease duration defined from onset of first non-Raynaud's symptom (ii) Not on any immunosuppressive treatment or prednisolone \>10 mg /day 8 weeks before recruitment
Aim 2 subject stratification:
(i) early SSc (≤3 years) and (ii) starting on immunosuppressive treatment either
1. MMF + Prednisolone or
2. Other immunosuppressive treatment in combination with MMF + Prednisolone
Exploratory aim subject stratification:
(i) VEDOSS or early SSc (≤3 years) with disease duration defined from onset of first non-Raynaud's symptom (ii) Not on any immunosuppressive treatment or prednisolone \>10 mg /day 8 weeks before recruitment
Exclusion Criteria
(i) Lactating or pregnancy (ii) Allergy or contraindications to hyoscine butylbromide (e.g. myasthenia gravis, prostatic enlargement with urinary retention, clinically significant GI obstruction or ileus) (iii) Contraindications to MRI (iv) Infections 4 weeks before baseline measurements (v) On antibiotics 4 weeks before baseline measurements, unless given for treatment of small intestinal bacterial overgrowth (SIBO), a complication of SSc.
(vi) Malignancy or suspected malignancy within the last 2 years (vii) Diabetes on treatment
(vi) Malignancy or suspected malignancy within the last 2 years (vii) Diabetes on treatment
Minimum Eligible Age
21 Years
Maximum Eligible Age
99 Years
Eligible Sex
ALL
Accepts Healthy Volunteers
No
Sponsors
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National University Hospital, Singapore
OTHER
Sponsor Role
collaborator
Tan Tock Seng Hospital
OTHER
Sponsor Role
collaborator
Changi General Hospital
OTHER
Sponsor Role
collaborator
Sengkang General Hospital
OTHER
Sponsor Role
collaborator
National University of Singapore
OTHER
Sponsor Role
collaborator
Nanyang Technological University
OTHER
Sponsor Role
collaborator
Duke-NUS Graduate Medical School
OTHER
Sponsor Role
collaborator
Singapore General Hospital
OTHER
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Andrea Low
Role: PRINCIPAL_INVESTIGATOR
Singapore General Hospital
Locations
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National University Hospital
Singapore, , Singapore
Site Status
RECRUITING
Singapore General Hospital
Singapore, , Singapore
Site Status
RECRUITING
Tan Tock Seng Hospital
Singapore, , Singapore
Site Status
RECRUITING
Changi General Hospital
Singapore, , Singapore
Site Status
RECRUITING
Sengkang General Hospital
Singapore, , Singapore
Site Status
RECRUITING
Countries
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Singapore
Central Contacts
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Facility Contacts
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Jing Wen Chua
Role: primary
Man Hua Aw
Role: primary
Kai Yan Lin
Role: primary
Cherlyn Wong
Role: primary
Wei Rui Goh
Role: primary
References
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Steen VD, Medsger TA. Changes in causes of death in systemic sclerosis, 1972-2002. Ann Rheum Dis. 2007 Jul;66(7):940-4. doi: 10.1136/ard.2006.066068. Epub 2007 Feb 28.
Reference Type
BACKGROUND
Barnes J, Mayes MD. Epidemiology of systemic sclerosis: incidence, prevalence, survival, risk factors, malignancy, and environmental triggers. Curr Opin Rheumatol. 2012 Mar;24(2):165-70. doi: 10.1097/BOR.0b013e32834ff2e8.
Reference Type
BACKGROUND
Ng X, Thumboo J, Low AH. Validation of the scleroderma health assessment questionnaire and quality of life in English and Chinese-speaking patients with systemic sclerosis. Int J Rheum Dis. 2012 Jun;15(3):268-76. doi: 10.1111/j.1756-185X.2012.01731.x. Epub 2012 Apr 29.
Reference Type
BACKGROUND
Santosa A, Tan CS, Teng GG, Fong W, Lim A, Law WG, Chan G, Ng SC, Low A. Lung and gastrointestinal complications are leading causes of death in SCORE, a multi-ethnic Singapore systemic sclerosis cohort. Scand J Rheumatol. 2016 Nov;45(6):499-506. doi: 10.3109/03009742.2016.1153141. Epub 2016 May 27.
Reference Type
BACKGROUND
Marie I, Ducrotte P, Denis P, Menard JF, Levesque H. Small intestinal bacterial overgrowth in systemic sclerosis. Rheumatology (Oxford). 2009 Oct;48(10):1314-9. doi: 10.1093/rheumatology/kep226. Epub 2009 Aug 20.
Reference Type
BACKGROUND
Lepri G, Guiducci S, Bellando-Randone S, Giani I, Bruni C, Blagojevic J, Carnesecchi G, Radicati A, Pucciani F, Marco MC. Evidence for oesophageal and anorectal involvement in very early systemic sclerosis (VEDOSS): report from a single VEDOSS/EUSTAR centre. Ann Rheum Dis. 2015 Jan;74(1):124-8. doi: 10.1136/annrheumdis-2013-203889. Epub 2013 Oct 15.
Reference Type
BACKGROUND
Avouac J, Fransen J, Walker UA, Riccieri V, Smith V, Muller C, Miniati I, Tarner IH, Randone SB, Cutolo M, Allanore Y, Distler O, Valentini G, Czirjak L, Muller-Ladner U, Furst DE, Tyndall A, Matucci-Cerinic M; EUSTAR Group. Preliminary criteria for the very early diagnosis of systemic sclerosis: results of a Delphi Consensus Study from EULAR Scleroderma Trials and Research Group. Ann Rheum Dis. 2011 Mar;70(3):476-81. doi: 10.1136/ard.2010.136929. Epub 2010 Nov 15.
Reference Type
BACKGROUND
McFarlane IM, Bhamra MS, Kreps A, Iqbal S, Al-Ani F, Saladini-Aponte C, Grant C, Singh S, Awwal K, Koci K, Saperstein Y, Arroyo-Mercado FM, Laskar DB, Atluri P. Gastrointestinal Manifestations of Systemic Sclerosis. Rheumatology (Sunnyvale). 2018;8(1):235. doi: 10.4172/2161-1149.1000235. Epub 2018 Mar 30.
Reference Type
BACKGROUND
Bruni C, Frech T, Manetti M, Rossi FW, Furst DE, De Paulis A, Rivellese F, Guiducci S, Matucci-Cerinic M, Bellando-Randone S. Vascular Leaking, a Pivotal and Early Pathogenetic Event in Systemic Sclerosis: Should the Door Be Closed? Front Immunol. 2018 Sep 7;9:2045. doi: 10.3389/fimmu.2018.02045. eCollection 2018.
Reference Type
BACKGROUND
Kawaguchi Y, Nakamura Y, Matsumoto I, Nishimagi E, Satoh T, Kuwana M, Sumida T, Hara M. Muscarinic-3 acetylcholine receptor autoantibody in patients with systemic sclerosis: contribution to severe gastrointestinal tract dysmotility. Ann Rheum Dis. 2009 May;68(5):710-4. doi: 10.1136/ard.2008.096545. Epub 2008 Sep 1.
Reference Type
BACKGROUND
Singh J, Mehendiratta V, Del Galdo F, Jimenez SA, Cohen S, DiMarino AJ, Rattan S. Immunoglobulins from scleroderma patients inhibit the muscarinic receptor activation in internal anal sphincter smooth muscle cells. Am J Physiol Gastrointest Liver Physiol. 2009 Dec;297(6):G1206-13. doi: 10.1152/ajpgi.00286.2009. Epub 2009 Sep 24.
Reference Type
BACKGROUND
Manetti M, Neumann E, Muller A, Schmeiser T, Saar P, Milia AF, Endlicher E, Roeb E, Messerini L, Matucci-Cerinic M, Ibba-Manneschi L, Muller-Ladner U. Endothelial/lymphocyte activation leads to prominent CD4+ T cell infiltration in the gastric mucosa of patients with systemic sclerosis. Arthritis Rheum. 2008 Sep;58(9):2866-73. doi: 10.1002/art.23806.
Reference Type
BACKGROUND
Taroni JN, Martyanov V, Huang CC, Mahoney JM, Hirano I, Shetuni B, Yang GY, Brenner D, Jung B, Wood TA, Bhattacharyya S, Almagor O, Lee J, Sirajuddin A, Varga J, Chang RW, Whitfield ML, Hinchcliff M. Molecular characterization of systemic sclerosis esophageal pathology identifies inflammatory and proliferative signatures. Arthritis Res Ther. 2015 Jul 29;17:194. doi: 10.1186/s13075-015-0695-1.
Reference Type
BACKGROUND
Johnson ME, Pioli PA, Whitfield ML. Gene expression profiling offers insights into the role of innate immune signaling in SSc. Semin Immunopathol. 2015 Sep;37(5):501-9. doi: 10.1007/s00281-015-0512-6. Epub 2015 Jul 30.
Reference Type
BACKGROUND
Hinchcliff M, Huang CC, Wood TA, Matthew Mahoney J, Martyanov V, Bhattacharyya S, Tamaki Z, Lee J, Carns M, Podlusky S, Sirajuddin A, Shah SJ, Chang RW, Lafyatis R, Varga J, Whitfield ML. Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis. J Invest Dermatol. 2013 Aug;133(8):1979-89. doi: 10.1038/jid.2013.130. Epub 2013 Mar 14.
Reference Type
BACKGROUND
Chakravarty EF, Martyanov V, Fiorentino D, Wood TA, Haddon DJ, Jarrell JA, Utz PJ, Genovese MC, Whitfield ML, Chung L. Gene expression changes reflect clinical response in a placebo-controlled randomized trial of abatacept in patients with diffuse cutaneous systemic sclerosis. Arthritis Res Ther. 2015 Jun 13;17(1):159. doi: 10.1186/s13075-015-0669-3.
Reference Type
BACKGROUND
Assassi S, Wang X, Chen G, Goldmuntz E, Keyes-Elstein L, Ying J, Wallace PK, Turner J, Zheng WJ, Pascual V, Varga J, Hinchcliff ME, Bellocchi C, McSweeney P, Furst DE, Nash RA, Crofford LJ, Welch B, Pinckney A, Mayes MD, Sullivan KM. Myeloablation followed by autologous stem cell transplantation normalises systemic sclerosis molecular signatures. Ann Rheum Dis. 2019 Oct;78(10):1371-1378. doi: 10.1136/annrheumdis-2019-215770. Epub 2019 Aug 7.
Reference Type
BACKGROUND
Taroni JN, Greene CS, Martyanov V, Wood TA, Christmann RB, Farber HW, Lafyatis RA, Denton CP, Hinchcliff ME, Pioli PA, Mahoney JM, Whitfield ML. A novel multi-network approach reveals tissue-specific cellular modulators of fibrosis in systemic sclerosis. Genome Med. 2017 Mar 23;9(1):27. doi: 10.1186/s13073-017-0417-1.
Reference Type
BACKGROUND
Papachristos DA, Nikpour M, Hair C, Stevens WM. Intravenous cyclophosphamide as a therapeutic option for severe refractory gastric antral vascular ectasia in systemic sclerosis. Intern Med J. 2015 Oct;45(10):1077-81. doi: 10.1111/imj.12883.
Reference Type
BACKGROUND
Raja J, Nihtyanova SI, Murray CD, Denton CP, Ong VH. Sustained benefit from intravenous immunoglobulin therapy for gastrointestinal involvement in systemic sclerosis. Rheumatology (Oxford). 2016 Jan;55(1):115-9. doi: 10.1093/rheumatology/kev318. Epub 2015 Aug 28.
Reference Type
BACKGROUND
Allanore Y, Distler O. Systemic sclerosis in 2014: Advances in cohort enrichment shape future of trial design. Nat Rev Rheumatol. 2015 Feb;11(2):72-4. doi: 10.1038/nrrheum.2014.222. Epub 2015 Jan 6.
Reference Type
BACKGROUND
Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M; Scleroderma Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006 Jun 22;354(25):2655-66. doi: 10.1056/NEJMoa055120.
Reference Type
BACKGROUND
Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM; Sclerodema Lung Study II Investigators. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016 Sep;4(9):708-719. doi: 10.1016/S2213-2600(16)30152-7. Epub 2016 Jul 25.
Reference Type
BACKGROUND
Sullivan KM, Goldmuntz EA, Keyes-Elstein L, McSweeney PA, Pinckney A, Welch B, Mayes MD, Nash RA, Crofford LJ, Eggleston B, Castina S, Griffith LM, Goldstein JS, Wallace D, Craciunescu O, Khanna D, Folz RJ, Goldin J, St Clair EW, Seibold JR, Phillips K, Mineishi S, Simms RW, Ballen K, Wener MH, Georges GE, Heimfeld S, Hosing C, Forman S, Kafaja S, Silver RM, Griffing L, Storek J, LeClercq S, Brasington R, Csuka ME, Bredeson C, Keever-Taylor C, Domsic RT, Kahaleh MB, Medsger T, Furst DE; SCOT Study Investigators. Myeloablative Autologous Stem-Cell Transplantation for Severe Scleroderma. N Engl J Med. 2018 Jan 4;378(1):35-47. doi: 10.1056/nejmoa1703327.
Reference Type
BACKGROUND
van Laar JM, Farge D, Sont JK, Naraghi K, Marjanovic Z, Larghero J, Schuerwegh AJ, Marijt EW, Vonk MC, Schattenberg AV, Matucci-Cerinic M, Voskuyl AE, van de Loosdrecht AA, Daikeler T, Kotter I, Schmalzing M, Martin T, Lioure B, Weiner SM, Kreuter A, Deligny C, Durand JM, Emery P, Machold KP, Sarrot-Reynauld F, Warnatz K, Adoue DF, Constans J, Tony HP, Del Papa N, Fassas A, Himsel A, Launay D, Lo Monaco A, Philippe P, Quere I, Rich E, Westhovens R, Griffiths B, Saccardi R, van den Hoogen FH, Fibbe WE, Socie G, Gratwohl A, Tyndall A; EBMT/EULAR Scleroderma Study Group. Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial. JAMA. 2014 Jun 25;311(24):2490-8. doi: 10.1001/jama.2014.6368.
Reference Type
BACKGROUND
Furst DE, Braun-Moscovic Y, Khanna D. Points to consider for clinical trials of the gastrointestinal tract in systemic sclerosis. Rheumatology (Oxford). 2017 Sep 1;56(suppl_5):v4-v11. doi: 10.1093/rheumatology/kex195.
Reference Type
BACKGROUND
Soussan M, Nicolas P, Schramm C, Katsahian S, Pop G, Fain O, Mekinian A. Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis. Medicine (Baltimore). 2015 Apr;94(14):e622. doi: 10.1097/MD.0000000000000622.
Reference Type
BACKGROUND
Lenze F, Wessling J, Bremer J, Ullerich H, Spieker T, Weckesser M, Gonschorrek S, Kannengiesser K, Rijcken E, Heidemann J, Luegering A, Schober O, Domschke W, Kucharzik T, Maaser C. Detection and differentiation of inflammatory versus fibromatous Crohn's disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation. Inflamm Bowel Dis. 2012 Dec;18(12):2252-60. doi: 10.1002/ibd.22930. Epub 2012 Feb 22.
Reference Type
BACKGROUND
Versari A, Pipitone N, Casali M, Jamar F, Pazzola G. Use of imaging techniques in large vessel vasculitis and related conditions. Q J Nucl Med Mol Imaging. 2018 Mar;62(1):34-39. doi: 10.23736/S1824-4785.17.03044-8. Epub 2017 Nov 22.
Reference Type
BACKGROUND
Einspieler I, Thurmel K, Pyka T, Eiber M, Wolfram S, Moog P, Reeps C, Essler M. Imaging large vessel vasculitis with fully integrated PET/MRI: a pilot study. Eur J Nucl Med Mol Imaging. 2015 Jun;42(7):1012-24. doi: 10.1007/s00259-015-3007-8. Epub 2015 Apr 16.
Reference Type
BACKGROUND
Beiderwellen K, Kinner S, Gomez B, Lenga L, Bellendorf A, Heusch P, Umutlu L, Langhorst J, Ruenzi M, Gerken G, Bockisch A, Lauenstein TC. Hybrid imaging of the bowel using PET/MR enterography: Feasibility and first results. Eur J Radiol. 2016 Feb;85(2):414-21. doi: 10.1016/j.ejrad.2015.12.008. Epub 2015 Dec 17.
Reference Type
BACKGROUND
Pellino G, Nicolai E, Catalano OA, Campione S, D'Armiento FP, Salvatore M, Cuocolo A, Selvaggi F. PET/MR Versus PET/CT Imaging: Impact on the Clinical Management of Small-Bowel Crohn's Disease. J Crohns Colitis. 2016 Mar;10(3):277-85. doi: 10.1093/ecco-jcc/jjv207. Epub 2015 Nov 15.
Reference Type
BACKGROUND
Catalano OA, Gee MS, Nicolai E, Selvaggi F, Pellino G, Cuocolo A, Luongo A, Catalano M, Rosen BR, Gervais D, Vangel MG, Soricelli A, Salvatore M. Evaluation of Quantitative PET/MR Enterography Biomarkers for Discrimination of Inflammatory Strictures from Fibrotic Strictures in Crohn Disease. Radiology. 2016 Mar;278(3):792-800. doi: 10.1148/radiol.2015150566. Epub 2015 Oct 5.
Reference Type
BACKGROUND
Marchesseau S, Ng SA, Wang YT, Xie W, Ng DC, Totman JJ, Low AHL. 18F-FDG PET-MRI with T1 MOLLI mapping to detect systemic sclerosis bowel inflammation and fibrosis. Eur J Radiol. 2018 Aug;105:289-295. doi: 10.1016/j.ejrad.2018.06.022. Epub 2018 Jun 26.
Reference Type
BACKGROUND
Freiman M, Perez-Rossello JM, Callahan MJ, Bittman M, Mulkern RV, Bousvaros A, Warfield SK. Characterization of fast and slow diffusion from diffusion-weighted MRI of pediatric Crohn's disease. J Magn Reson Imaging. 2013 Jan;37(1):156-63. doi: 10.1002/jmri.23781. Epub 2012 Aug 24.
Reference Type
BACKGROUND
Zhang MC, Li XH, Huang SY, Mao R, Fang ZN, Cao QH, Zhang ZW, Yan X, Chen MH, Li ZP, Sun CH, Feng ST. IVIM with fractional perfusion as a novel biomarker for detecting and grading intestinal fibrosis in Crohn's disease. Eur Radiol. 2019 Jun;29(6):3069-3078. doi: 10.1007/s00330-018-5848-6. Epub 2018 Dec 13.
Reference Type
BACKGROUND
Le Bihan D. What can we see with IVIM MRI? Neuroimage. 2019 Feb 15;187:56-67. doi: 10.1016/j.neuroimage.2017.12.062. Epub 2017 Dec 22.
Reference Type
BACKGROUND
Volkmann ER. Intestinal microbiome in scleroderma: recent progress. Curr Opin Rheumatol. 2017 Nov;29(6):553-560. doi: 10.1097/BOR.0000000000000429.
Reference Type
BACKGROUND
Volkmann ER, Hoffmann-Vold AM, Chang YL, Jacobs JP, Tillisch K, Mayer EA, Clements PJ, Hov JR, Kummen M, Midtvedt O, Lagishetty V, Chang L, Labus JS, Molberg O, Braun J. Systemic sclerosis is associated with specific alterations in gastrointestinal microbiota in two independent cohorts. BMJ Open Gastroenterol. 2017 Apr 1;4(1):e000134. doi: 10.1136/bmjgast-2017-000134. eCollection 2017.
Reference Type
BACKGROUND
Ishikawa D, Sasaki T, Osada T, Kuwahara-Arai K, Haga K, Shibuya T, Hiramatsu K, Watanabe S. Changes in Intestinal Microbiota Following Combination Therapy with Fecal Microbial Transplantation and Antibiotics for Ulcerative Colitis. Inflamm Bowel Dis. 2017 Jan;23(1):116-125. doi: 10.1097/MIB.0000000000000975.
Reference Type
BACKGROUND
Low AHL, Teng GG, Pettersson S, de Sessions PF, Ho EXP, Fan Q, Chu CW, Law AHN, Santosa A, Lim AYN, Wang YT, Haaland B, Thumboo J. A double-blind randomized placebo-controlled trial of probiotics in systemic sclerosis associated gastrointestinal disease. Semin Arthritis Rheum. 2019 Dec;49(3):411-419. doi: 10.1016/j.semarthrit.2019.05.006. Epub 2019 May 23.
Reference Type
BACKGROUND
Bjerrum JT, Wang Y, Hao F, Coskun M, Ludwig C, Gunther U, Nielsen OH. Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn's disease and healthy individuals. Metabolomics. 2015;11:122-133. doi: 10.1007/s11306-014-0677-3. Epub 2014 Jun 1.
Reference Type
BACKGROUND
Waclawikova B, El Aidy S. Role of Microbiota and Tryptophan Metabolites in the Remote Effect of Intestinal Inflammation on Brain and Depression. Pharmaceuticals (Basel). 2018 Jun 25;11(3):63. doi: 10.3390/ph11030063.
Reference Type
BACKGROUND
Andreasson K, Alrawi Z, Persson A, Jonsson G, Marsal J. Intestinal dysbiosis is common in systemic sclerosis and associated with gastrointestinal and extraintestinal features of disease. Arthritis Res Ther. 2016 Nov 29;18(1):278. doi: 10.1186/s13075-016-1182-z.
Reference Type
BACKGROUND
van den Hoogen F, Khanna D, Fransen J, Johnson SR, Baron M, Tyndall A, Matucci-Cerinic M, Naden RP, Medsger TA Jr, Carreira PE, Riemekasten G, Clements PJ, Denton CP, Distler O, Allanore Y, Furst DE, Gabrielli A, Mayes MD, van Laar JM, Seibold JR, Czirjak L, Steen VD, Inanc M, Kowal-Bielecka O, Muller-Ladner U, Valentini G, Veale DJ, Vonk MC, Walker UA, Chung L, Collier DH, Csuka ME, Fessler BJ, Guiducci S, Herrick A, Hsu VM, Jimenez S, Kahaleh B, Merkel PA, Sierakowski S, Silver RM, Simms RW, Varga J, Pope JE. 2013 classification criteria for systemic sclerosis: an American College of Rheumatology/European League against Rheumatism collaborative initiative. Arthritis Rheum. 2013 Nov;65(11):2737-47. doi: 10.1002/art.38098. Epub 2013 Oct 3.
Reference Type
BACKGROUND
Khanna D, Furst DE, Clements PJ, Allanore Y, Baron M, Czirjak L, Distler O, Foeldvari I, Kuwana M, Matucci-Cerinic M, Mayes M, Medsger T Jr, Merkel PA, Pope JE, Seibold JR, Steen V, Stevens W, Denton CP. Standardization of the modified Rodnan skin score for use in clinical trials of systemic sclerosis. J Scleroderma Relat Disord. 2017 Jan-Apr;2(1):11-18. doi: 10.5301/jsrd.5000231.
Reference Type
BACKGROUND
Sprooten RTM, Lenaerts K, Braeken DCW, Grimbergen I, Rutten EP, Wouters EFM, Rohde GGU. Increased Small Intestinal Permeability during Severe Acute Exacerbations of COPD. Respiration. 2018;95(5):334-342. doi: 10.1159/000485935. Epub 2018 Jan 25.
Reference Type
BACKGROUND
Rizzetto L, Fava F, Tuohy KM, Selmi C. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex. J Autoimmun. 2018 Aug;92:12-34. doi: 10.1016/j.jaut.2018.05.008. Epub 2018 Jun 1.
Reference Type
BACKGROUND
Khanna D, Hays RD, Maranian P, Seibold JR, Impens A, Mayes MD, Clements PJ, Getzug T, Fathi N, Bechtel A, Furst DE. Reliability and validity of the University of California, Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. Arthritis Rheum. 2009 Sep 15;61(9):1257-63. doi: 10.1002/art.24730.
Reference Type
BACKGROUND
Low AHL, Xin X, Law WG, Teng GG, Santosa A, Lim A, Chan G, Ng SC, Thumboo J. Validation of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument 2.0 in English- and Chinese-speaking patients in a multi-ethnic Singapore systemic sclerosis cohort. Clin Rheumatol. 2017 Jul;36(7):1643-1648. doi: 10.1007/s10067-016-3529-x. Epub 2017 Jan 5.
Reference Type
BACKGROUND
Khanna D, Furst DE, Maranian P, Seibold JR, Impens A, Mayes MD, Clements PJ, Getzug T, Hays RD. Minimally important differences of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument. J Rheumatol. 2011 Sep;38(9):1920-4. doi: 10.3899/jrheum.110225. Epub 2011 Jul 1.
Reference Type
BACKGROUND
Korecka A, Dona A, Lahiri S, Tett AJ, Al-Asmakh M, Braniste V, D'Arienzo R, Abbaspour A, Reichardt N, Fujii-Kuriyama Y, Rafter J, Narbad A, Holmes E, Nicholson J, Arulampalam V, Pettersson S. Bidirectional communication between the Aryl hydrocarbon Receptor (AhR) and the microbiome tunes host metabolism. NPJ Biofilms Microbiomes. 2016 Aug 24;2:16014. doi: 10.1038/npjbiofilms.2016.14. eCollection 2016.
Reference Type
BACKGROUND
Thion MS, Low D, Silvin A, Chen J, Grisel P, Schulte-Schrepping J, Blecher R, Ulas T, Squarzoni P, Hoeffel G, Coulpier F, Siopi E, David FS, Scholz C, Shihui F, Lum J, Amoyo AA, Larbi A, Poidinger M, Buttgereit A, Lledo PM, Greter M, Chan JKY, Amit I, Beyer M, Schultze JL, Schlitzer A, Pettersson S, Ginhoux F, Garel S. Microbiome Influences Prenatal and Adult Microglia in a Sex-Specific Manner. Cell. 2018 Jan 25;172(3):500-516.e16. doi: 10.1016/j.cell.2017.11.042. Epub 2017 Dec 21.
Reference Type
BACKGROUND
Bjerrum JT, Steenholdt C, Ainsworth M, Nielsen OH, Reed MA, Atkins K, Gunther UL, Hao F, Wang Y. Metabonomics uncovers a reversible proatherogenic lipid profile during infliximab therapy of inflammatory bowel disease. BMC Med. 2017 Oct 16;15(1):184. doi: 10.1186/s12916-017-0949-7.
Reference Type
BACKGROUND
Rutten EPA, Lenaerts K, Buurman WA, Wouters EFM. Disturbed intestinal integrity in patients with COPD: effects of activities of daily living. Chest. 2014 Feb;145(2):245-252. doi: 10.1378/chest.13-0584.
Reference Type
BACKGROUND
Morrisroe K, Sudararajan V, Stevens W, Sahhar J, Zochling J, Roddy J, Proudman S, Nikpour M. Work productivity in systemic sclerosis, its economic burden and association with health-related quality of life. Rheumatology (Oxford). 2018 Jan 1;57(1):73-83. doi: 10.1093/rheumatology/kex362.
Reference Type
BACKGROUND
Forbes A, Marie I. Gastrointestinal complications: the most frequent internal complications of systemic sclerosis. Rheumatology (Oxford). 2009 Jun;48 Suppl 3:iii36-9. doi: 10.1093/rheumatology/ken485.
Reference Type
BACKGROUND
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
PM-SScGI-01
Identifier Type: -
Identifier Source: org_study_id