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

Systemic Sclerosis Clinical Trial

— Pre Med SSc GI  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04630782
• Other study ID #: PM-SScGI-01
• Status: Recruiting
• Start date: April 9, 2020
• Est. completion date: January 31, 2023

Study information

• Verified date: November 2020
• Source: Singapore General Hospital
• Contact: Andrea Low
• Phone: +6563214028
• Email: andrea.low.h.l[@]singhealth.com.sg
• Is FDA regulated: No
• Study type: Observational

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 70
• Est. completion date: January 31, 2023
• Est. primary completion date: January 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Digestive System Diseases
• Gastrointestinal Diseases
• Scleroderma
• Scleroderma, Diffuse
• Scleroderma, Systemic
• Sclerosis
• Systemic Sclerosis

Intervention

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.

Locations

Country	Name	City	State
Singapore	Changi General Hospital	Singapore
Singapore	National University Hospital	Singapore
Singapore	Sengkang General Hospital	Singapore
Singapore	Singapore General Hospital	Singapore
Singapore	Tan Tock Seng Hospital	Singapore

Sponsors (8)

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

Country where clinical trial is conducted

Singapore, 

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* Note: There are 57 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline
Primary	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	Baseline, 6-month and 12-month
Secondary	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.	Baseline and 12-month
Secondary	Stool biomarkers	Faecal-calprotectin, stool microbiota diversity, relative abundance according to taxonomic classifications.	baseline, 6 and 12 months