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

NCT06827977 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HSC-MS-24-0630
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Constipation; Bloating

Keywords

Systemic Sclerosis

Outcome Measures

Primary Outcomes (9)

• 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)

  This consists of 34 questions covering domains such as diarrhea, constipation, abdominal pain, nausea, bloating, gastroesophageal reflux, fecal incontinence, and emotional well-being related to GI symptoms. Each item is scored on a Likert scale ranging from 0 to 3 (0 = none, 1 = mild, 2 = moderate, 3 = severe), with higher scores indicating greater symptom severity. Domain scores are calculated as the sum of responses to items within the domain, and a total score is calculated by summing all domain scores, representing the overall GI symptom burden. Total score will be reported, and the total score ranges from 0-102.

  pre-transplant , post-treatment at week 12

• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20 summary score)

  The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.

  pre-transplant , post-treatment at week 12

• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (UDI-6 subscale score)

  The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.

  pre-transplant , post-treatment at week 12

• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (POPDI-6 subscale score)

  The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.

  pre-transplant , post-treatment at week 12

• Change in Pelvic Floor Distress as Assessed by the Pelvic Floor Distress Inventory Questionnaire-20 (CRADI-8 subscale score)

  The Pelvic Floor Distress Inventory Questionnaire-20 (PFDI-20) is composed of 3 subscales: the Urinary Distress Inventory-6 (UDI-6), the Pelvic Organ Prolapse Distress Inventory-6 (POPDI-6), and the Colorectal-Anal Distress Inventory-8 (CRADI-8). For each question, the participant must indicate how much bowl, bladder, or pelvic symptoms have been bothering them in the past 3 months on a 4-point scale that ranges from "not at all" (0) to "quite a bit" (4). Total score for each subscale ranges from 0 to 100, with a higher score indicating worse distress. The sum of the 3 subscales are added together to get the PFDI-20 summary score, which ranges from 0 to 300, with a higher score indicating worse distress.

  pre-transplant , post-treatment at week 12

• Change in symptoms and signs of constipation as assessed by score on the Patient Assessment of Constipation Symptoms (PAC-SYM) scale

  The PAC-SYM is a 12-item questionnaire that assesses abdominal, rectal, and stool symptoms, with each item scored from 0 (No symptoms) to 4 (Very severe symptoms), for a total score range of 0-48, with a higher score indicating worse constipation severity.

  pre-transplant , post-treatment at week 12

• Change in Gastrointestinal Symptom Severity as Assessed by the Patient Assessment of Gastrointestinal Disorders-Symptom Severity Index (PAGI-SYM)

  Total score ranges from 0 (none or absent) to 5 (very severe), with a higher score indicating a worse outcome.

  pre-transplant , post-treatment at week 12

• Number of participants who show an improvement in constipation and/or significant bloating symptoms as indicated by the stool diary

  from baseline to end of study (week 12)

• Change in gut transit times (assessed by Sitz markers and X-ray)

  pre-transplant , post-treatment at week 12

Secondary Outcomes (3)

• Change in immunoglobulin A (IgA) antibody sequence

  pre-transplant , week 12 post-transplant

• Change in alpha diversity of the microbiome

  pre-transplant , week 12 post-transplant

• Change in beta diversity of the microbiome

  pre-transplant , week 12 post-transplant

Study Arms (2)

PRIM-DJ2727

EXPERIMENTAL

Drug: PRIM-DJ2727

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

PRIM-DJ2727 DRUG

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 be done at baseline and week 11, 50 g of filtered, frozen stool in 250 mL of 0.85% sodium chloride (NaCl) will be used.

PRIM-DJ2727

Placebo DRUG

Placebo will be administered as capsules from week 2-10 and as enema at baseline and week 11.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Constipation; Scleroderma, Systemic

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Study Officials

• Zsuzsanna McMahan, MD, MHS

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zsuzsanna McMahan, MD, MHS

CONTACT

713-500-7531; Zsuzsanna.H.McMahan@uth.tmc.edu

Ashish P Balar, MBBS, MPH

CONTACT

713-500-4409; Ashish.P.Balar@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine, Co-Director of the UTHealth Scleroderma Center

Study Record Dates

• First Submitted: February 9, 2025
• First Posted: February 14, 2025
• Study Start: March 3, 2025
• Primary Completion (Estimated): May 30, 2026
• Study Completion (Estimated): September 26, 2026
• Last Updated: June 26, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)