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Systemic SclerosisPre Med SSc GINCT04630782

Evaluating Gut Imaging and Stool Biomarkers in Patients With Scleroderma-associated Gastrointestinal Disease

An observational study of Systemic Sclerosis and Scleroderma, run by Singapore General Hospital at 5 sites in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 21 to 99 years
Conditions the study is for
Systemic Sclerosis, Scleroderma
What is being tested?
PET-MRI scan
Type of treatment
Injection or infusion
How many people
70 participants
Where
5 sitesSingapore
Study dates
9 Apr 2020to 31 Jan 2023
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: Participants will be recruited from Singapore General Hospital, National University Hospital, Tan Tock Seng Hospital, Changi General Hospital and Sengkang General Hospital

Who may be able to join

  • ≥ 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:
  • 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:
  • early SSc (≤3 years) and (ii) starting on immunosuppressive treatment either
  • MMF + Prednisolone or
Show all 9Show fewer
  • Other immunosuppressive treatment in combination with MMF + Prednisolone
  • Exploratory aim subject stratification:
  • 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

Who cannot join

  • 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.
  • Malignancy or suspected malignancy within the last 2 years (vii) Diabetes on treatment

Trial locations and contacts

5 sites in 1 country.

Andrea Low contact

+6563214028

andrea.low.h.l@singhealth.com.sg

5 sites in 1 country

Singapore5 sites, 5 recruiting

  • National University Hospital

    Singapore, 119074

    Jing Wen Chua, +6591691093, jing_wen_chua@nuhs.edu.sg

    Gim Gee Teng

    Recruiting

  • Singapore General Hospital

    Singapore, 169608

    Man Hua Aw, +6596643192, aw.man.hua@sgh.com.sg

    Sue-Ann Ng

    Recruiting

  • Tan Tock Seng Hospital

    Singapore, 308433

    Kai Yan Lin, +6597157598, kai_yan_lin@ttsh.com.sg

    Weng Giap Law

    Recruiting

  • Changi General Hospital

    Singapore, 529889

    Cherlyn Wong, +6589215070, cherlyn.wong@sgh.com.sg

    Anindita Santosa

    Recruiting

  • Sengkang General Hospital

    Singapore, 544886

    Wei Rui Goh, +6593253619, goh.wei.rui@sgh.com.sg

    Nur Emillia Binte Roslan

    Recruiting

Other trials in Singapore

About this study

Official title: Precision Medicine in Systemic Sclerosis Gastrointestinal Disease: Evaluating Imaging and Stool Biomarkers for Differentiating Disease Stages and Treatment Responses

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.

Read more

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.

Read the detailed description
  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.
Being tested
PET-MRI scan
Keywords
Systemic Sclerosis, Imaging, Diagnostic, MRI Scans, PET-MRI Scan
Medical subject headings
Scleroderma, Systemic, Scleroderma, Diffuse, Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PET-MRI scanDiagnostic 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.

Study groups in NCT04630782
Study groupRoleWhat they receive
Aim 1The 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.
Receives: Diagnostic Test: PET-MRI scan
Aim 2In 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.
Receives: Diagnostic Test: PET-MRI scan
Exploratory aimIn 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.
Receives: Diagnostic Test: PET-MRI scan

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Inflammatory or fibrosis FDG-PET-MRI imaging biomarkers in VEDOSS/early SSc or late SSc patients not on immunosuppresive treatment

    PET-MRI imaging biomarkers: Inflammatory biomarker: PET SUV tissue to background ratio (TBR); fibrosis biomarker: native T1-MOLLI value.

    Measured: Baseline

  2. Inflammatory biomarkers on FDG-PET-MRI imaging after 6 months (primary endpoint) and 12 months (secondary endpoint) of Mycophenolate mofetil treatment.

    Change in PET SUV TBR from baseline at 6 months (Primary endpoint) and 12 months (secondary endpoint) following Mycophenolate mofetil treatment

    Measured: Baseline, 6-month and 12-month

Secondary outcomes (2)

  1. FDG-PET-MRI imaging over one year in patients with VEDOSS/early SSc not on immunosuppresive treatment

    Change in PET SUV TBR, Native T1-MOLLI value, GIT score from baseline at 12 months.

    Measured: Baseline and 12-month

  2. Stool biomarkers

    Faecal-calprotectin, stool microbiota diversity, relative abundance according to taxonomic classifications.

    Measured: baseline, 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2020
  2. Study start9 Apr 2020
  3. Primary completion31 Jan 2023 (estimated)
  4. Study completion31 Jan 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
70 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04630782
Sponsor's protocol ID
PM-SScGI-01
Acronym
Pre Med SSc GI
Status last verified
Nov 2020
First submitted
12 Mar 2020
Last updated
24 Nov 2020
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 17329309

  • 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.

    PubMed 22269658

  • 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.

    PubMed 22709488

  • 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.

    PubMed 27232525

  • 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.

    PubMed 19696066

  • 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.

    PubMed 24130266

  • 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.

    PubMed 21081523

  • 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.

    PubMed 30057856

  • 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.

    PubMed 30245695

  • 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.

    PubMed 18762475

  • 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.

    PubMed 19779020

  • 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.

    PubMed 18759276

  • 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.

    PubMed 26220546

  • 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.

    PubMed 26223504

  • 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.

    PubMed 23677167

Questions about this trial

What is this clinical trial studying?

An observational study of Systemic Sclerosis and Scleroderma, run by Singapore General Hospital at 5 sites in Singapore.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 24 Nov 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Andrea Low (+6563214028, andrea.low.h.l@singhealth.com.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Inflammatory or fibrosis FDG-PET-MRI imaging biomarkers in VEDOSS/early SSc or late SSc patients not on immunosuppresive treatment (time frame: Baseline). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04630782, which also lists 57 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Nov 2020.

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