Clinical trial NCT04630782: Evaluating Gut Imaging and Stool Biomarkers in Patients With Scleroderma-associated Gastrointestinal Disease
Official title: Precision Medicine in Systemic Sclerosis Gastrointestinal Disease: Evaluating Imaging and Stool Biomarkers for Differentiating Disease Stages and Treatment Responses
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Systemic Sclerosis
Scleroderma
Keywords: Systemic Sclerosis
Imaging, Diagnostic
MRI Scans
PET-MRI Scan
Lead sponsor: Singapore General Hospital
Sponsor class: OTHER
Collaborators: name: National University Hospital, Singapore
name: Tan Tock Seng Hospital
name: Changi General Hospital
name: Sengkang General Hospital
name: National University of Singapore
name: Nanyang Technological University
name: Duke-NUS Graduate Medical School
First posted: 2020-11-16
Enrollment: 70
Sex: ALL
Minimum age (years): 21
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Inflammatory or fibrosis FDG-PET-MRI imaging biomarkers in VEDOSS/early SSc or late SSc patients not on immunosuppresive treatment
timeFrame: Baseline
measure: Inflammatory biomarkers on FDG-PET-MRI imaging after 6 months (primary endpoint) and 12 months (secondary endpoint) of Mycophenolate mofetil treatment.
timeFrame: Baseline, 6-month and 12-month
Secondary outcomes:
measure: FDG-PET-MRI imaging over one year in patients with VEDOSS/early SSc not on immunosuppresive treatment
timeFrame: Baseline and 12-month
measure: Stool biomarkers
timeFrame: baseline, 6 and 12 months
Other outcomes:
Locations:
city: Singapore
country: Singapore
facility: National University Hospital
city: Singapore
country: Singapore
facility: Singapore General Hospital
city: Singapore
country: Singapore
facility: Tan Tock Seng Hospital
city: Singapore
country: Singapore
facility: Changi General Hospital
city: Singapore
country: Singapore
facility: Sengkang General Hospital
Study officials:
affiliation: Singapore General Hospital
name: Andrea Low
role: PRINCIPAL_INVESTIGATOR
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