Evaluating Gut Imaging and Stool Biomarkers in Patients With Scleroderma-associated Gastrointestinal Disease (Pre Med SSc GI)

November 23, 2020 updated by: Singapore General Hospital

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.

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Observational

Enrollment (Anticipated)

70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Singapore
      • Singapore, Singapore, 169608
        • Recruiting
        • Singapore General Hospital
        • Contact:
        • Sub-Investigator:
          • Sue-Ann Ng
        • Sub-Investigator:
          • Cassandra Hong
        • Sub-Investigator:
          • Wanying Xie
        • Sub-Investigator:
          • Julian Thumboo
        • Principal Investigator:
          • Andrea Low
      • Singapore, Singapore, 308433
        • Recruiting
        • Tan Tock Seng Hospital
        • Contact:
        • Principal Investigator:
          • Weng Giap Law
        • Sub-Investigator:
          • Grace Chan
      • Singapore, Singapore, 119074
        • Recruiting
        • National University Hospital
        • Contact:
        • Principal Investigator:
          • Gim Gee Teng
        • Sub-Investigator:
          • Amelia Santosa
      • Singapore, Singapore, 529889
        • Recruiting
        • Changi General Hospital
        • Contact:
        • Principal Investigator:
          • Anindita Santosa
      • Singapore, Singapore, 544886
        • Recruiting
        • Sengkang General Hospital
        • Contact:
        • Principal Investigator:
          • Nur Emillia Binte Roslan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 97 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

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

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Diagnostic test: 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.
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.
Diagnostic test: 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.
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.
Diagnostic test: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Inflammatory or fibrosis FDG-PET-MRI imaging biomarkers in VEDOSS/early SSc or late SSc patients not on immunosuppresive treatment
Time Frame: Baseline
PET-MRI imaging biomarkers: Inflammatory biomarker: PET SUV tissue to background ratio (TBR); fibrosis biomarker: native T1-MOLLI value.
Baseline
Inflammatory biomarkers on FDG-PET-MRI imaging after 6 months (primary endpoint) and 12 months (secondary endpoint) of Mycophenolate mofetil treatment.
Time Frame: Baseline, 6-month and 12-month
Change in PET SUV TBR from baseline at 6 months (Primary endpoint) and 12 months (secondary endpoint) following Mycophenolate mofetil treatment
Baseline, 6-month and 12-month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
FDG-PET-MRI imaging over one year in patients with VEDOSS/early SSc not on immunosuppresive treatment
Time Frame: Baseline and 12-month
Change in PET SUV TBR, Native T1-MOLLI value, GIT score from baseline at 12 months.
Baseline and 12-month
Stool biomarkers
Time Frame: baseline, 6 and 12 months
Faecal-calprotectin, stool microbiota diversity, relative abundance according to taxonomic classifications.
baseline, 6 and 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Singapore General Hospital

Collaborators

National University Hospital, Singapore
Tan Tock Seng Hospital
Nanyang Technological University
Changi General Hospital
National University, Singapore
Sengkang General Hospital
Duke-NUS Graduate Medical School

Investigators

  • Principal Investigator: Andrea Low, Singapore General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 9, 2020

Primary Completion (Anticipated)

January 31, 2023

Study Completion (Anticipated)

January 31, 2023

Study Registration Dates

First Submitted

March 12, 2020

First Submitted That Met QC Criteria

November 13, 2020

First Posted (Actual)

November 16, 2020

Study Record Updates

Last Update Posted (Actual)

November 24, 2020

Last Update Submitted That Met QC Criteria

November 23, 2020

Last Verified

November 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PM-SScGI-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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