A Study of Microbiome Transplantation for the Treatment of Constipation and/or Significant Bloating in Patients With Systemic Sclerosis

Overview

The purpose of this study is to characterize the intestinal flora in subjects with systemic sclerosis-related constipation and/or significant bloating and to determine safety and trends in improvements in the diversity of colonic microbiome and patient symptoms following the administration of either frozen or lyophilized PRIM-DJ2727 microbiota.

Detailed description

The purpose of this study is to evaluate the tolerability and safety of frozen and lyophilized microbiome transplant product (PRIM- DJ2727), to characterize the microbiome (α-diversity and β-diversity) and metabolome in patients with Systemic Sclerosis (SSc)-related constipation and/or significant bloating, to examine improvement in constipation and/or significant bloating after microbiome transplant, to examine improved colonic transit after microbiome transplant, to examine subjective global improvement and improvement in SSc disease characteristics, to monitor change in concentration of systemic and fecal inflammatory markers, and to monitor for change in fecal short-chain fatty acids and metabolome.

Interventions

• Drug PRIM-DJ2727
  For oral administration, each dose will contain the number of capsules needed to deliver the lyophilized intestinal bacteria powder derived after lyophilization of 60 g of filtered stool in 300 mL 0.85% NaCl and 2% mannitol. Participants will take the capsules (5-6 capsules twice weekly) from week 2 through week 10. Capsules will be taken over a period of up to one hour to maximize tolerance and ensure the capsules are not expelled by vomiting. For administration via retention enema, which will
• Drug Placebo
  Placebo will be administered as capsules from week 2-10 and as enema at baseline and week 11.

Primary outcome measures

• Change in symptoms and signs of constipation and/or significant bloating as assessed by total score on the University of California, Los Angeles Gastrointestinal Tract Questionnaire, version 2.0 (UCLA GIT 2.0) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20 summary score) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (UDI-6 subscale score) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (POPDI-6 subscale score) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (CRADI-8 subscale score) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in symptoms and signs of constipation as assessed by score on the Patient Assessment of Constipation Symptoms (PAC-SYM) scale [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in Gastrointestinal Symptom Severity as Assessed by the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Number of participants who show an improvement in constipation and/or significant bloating symptoms as indicated by the stool diary [Time frame: from baseline to end of study (week 12)]
• Change in gut transit times (assessed by Sitz markers and X-ray) [Time frame: pre-transplant, post-treatment within weeks 11 to 12]

Secondary outcome measures (2)

• Change in alpha diversity of the microbiome [Time frame: pre-transplant, post-treatment within weeks 11 to 12]
• Change in beta diversity of the microbiome [Time frame: pre-transplant, post-treatment within weeks 11 to 12]

Eligibility criteria

Inclusion criteria

• Are seen in the UT Houston Scleroderma Center (UTHSC)
• Meet 2013 American college of rheumatology (ACR)/European league against rheumatism (EULAR) criteria or CREST criteria for SSc
• Meet Rome IV criteria for constipation and/or significant bloating
• Subject willing to sign an informed consent form
• Subject deemed likely to survive for ≥ 1 year after enrollment
• Able to follow study procedure and follow-up
• Sexually active male and female subjects of childbearing potential must agree to use an effective method of birth control during the treatment and follow-up period
• Female subjects of childbearing potential must have a negative pregnancy test in the 72 hours before the procedure
• Subjects who agree to adhere to a stable diet for at least 4 weeks before joining the study and throughout the study
• Subjects must have an attending physician who will provide non-transplant care for the subject

Exclusion criteria

• Subjects with constipation and/or significant bloating from causes not attributed to SSc as determined by the treating physician (e.g., inflammatory bowel disease, medication, significant diabetes, or hypothyroidism, etc.)
• Subjects unwilling to stop taking probiotic supplements during the duration of the study
• Subjects that have post-total or hemicolectomy or the presence of a colostomy
• Subjects unable to tolerate microbiome transplant via enema for any reason or swallow capsules
• Subjects requiring systemic antibiotic therapy 4 weeks before the study
• If subjects are on immunosuppression, the immunosuppression dose should be stable for at least 4 weeks before study enrollment

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 1 center

• The University of Texas Health Science Center at Houston — Houston

Identifiers

NCT: NCT06827977 · HSC-MS-24-0630

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗