Open Label Study to Assess Safety & Efficacy of QD for Induction of Remission in Pediatric Patients with UC

Not Applicable

Completed

• Conditions: Ulcerative Colitis; Inflammatory Bowel Diseases

• Registration Number: NCT06777706
• Lead Sponsor: Shaare Zedek Medical Center

Brief Summary

To date, there are no reports on the use of QD in pediatric patients with UC. There is a great need to increase the repertoire of anti-inflammatory interventions for remission induction, especially in children given the notorious side effects of steroids on growth. Importantly, no prescription is needed to acquire QD, as this is a food supplement that can be purchased over the counter. We wish to assess the efficacy and safety of QD as induction therapy in pediatric patients with mild-moderate active UC.

Detailed Description

This is a prospective open-label pilot study in two Pediatric IBD centers at Schneider Children's Medical Center of Israel and Share Zedek Medical Center. Pediatric UC patients at both participating centers will be screened during clinic visits for eligibility to participate in the study. Eligible patients are 4-17.9 years old, with at least one month history of UC, with mild to moderate active UC, defined by a PUCAI score of 10-60, despite current treatment. Normal liver enzymes obtained within one most prior to initiation of the study is required. The study will be presented to the families and once it is established that the patient fulfills the inclusion criteria, informed written consent will be obtained from the patient and parents.

Enrollment:

At enrolment patients will be examined and explicit clinical, medical and demographic data will be documented. PUCAI16 and TUMMY-UC (patient reported outcome developed specifically for pediatric UC patients17) scores will be determined. Extent of disease will be documented according to the last available colonoscopy, using the Montreal classification definitions (additional endoscopic evaluation is not required for the study). Laboratory work including CBC, albumin, AST, ALT, ESR and CRP. A stool sample will be obtained and kept at -800C for future analyses (see below). In addition, a baseline echocardiography will be performed to assess for PAH prior to initiation of QD (see below). Patients of child bearing potential will be advised to safeguard against pregnancy.

Following completion of enrollment and initial testing patients will receive QD (see dosing regimens below). QD will be provided as oral capsules. Patients who are not able to swallow the capsules will be instructed to open then and give it with yogurt/soft food. Patients will be instructed to continue taking their maintenance medication as prescribed by their treating physician throughout the entire study period, without any changes.

Day 3-4:

Patients will be contacted via telephone and questioned regarding any adverse effects, and specifically headaches, along with colitis-associated clinical features.

Week 3:

Patients will be seen in clinic, and will also be examined, as part of routine clinical care. Clinical data will be obtained, including PUCAI and TUMMY-UC. Prior to this visit, patients will complete blood work including CBC, chemistry panel and CRP. A stool sample will be collected at this clinic visit.

Week 6:

Patients will be seen in clinic, and will also be examined, as part of routine clinical care. Clinical data will be obtained, including PUCAI and TUMMY-UC. Patients will also complete prior to this visit blood work including CBC, chemistry panel and CRP. An additional stool sample will be obtained and kept at -80 degrees celsius for future analyses. Finally, a repeated echocardiography will be completed. At this timepoint, the study will be completed.

Termination visit:

If the study will be terminated prior to completion of the 6 weeks of QD therapy (see criteria below) the patient will be seen in clinic for a "termination visit". In this visit clinical data will be obtained, including PUCAI and TUMMY-UC. Patients will also complete prior to this visit blood work including CBC, chemistry panel and CRP. An additional stool sample will be obtained and kept at -80 degrees celsius. for future analyses.

At each study visit, patients of child bearing potential will be asked if they are pregnant.

Study Timeline

• Study First Submitted: 2022-05-04
• Study Start: 2023-01-01
• Primary Completion: 2024-09-01
• Study Completion: 2024-09-01
• Status Verified: 2025-01
• Study First Submitted QC: 2025-01-15
• Last Update Submitted: 2025-01-15
• Study First Posted: 2025-01-16
• Last Update Posted: 2025-01-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Established diagnosis of UC for at least one month based on accepted criteria15.
2. Age 4-17.9 years old (inclusive).
3. Weight ≥ 15kg
4. PUCAI 10-60 at enrollment (reflecting mild-moderate UC).
5. If a patient is receiving oral 5-ASA, the dose must be stable for at least 4 weeks prior to inclusion.
6. If patient is receiving immunomodulator medication (azathioprine or 6- mercaptopurine), dose must be stable for at least 3 months prior to inclusion.
7. If a patient is on topical 5-ASA (suppositories or enema) the dose must be stable for at least 2 weeks prior to inclusion and will not be altered throughout the 6-week study period.
8. Negative stool culture, parasites and clostridium difficile testing.

Exclusion Criteria

1. Acute severe colitis (PUCAI>65).
2. Patient with chronic renal or liver disease, hypertension, cardiovascular disease, cerebrovascular disease, chronic pancreatitis, diabetes mellitus, gallstone disease, previous malignancy, uncontrolled migraines or neurological disorders.
3. Abnormal liver enzymes (ALT, AST, GGT) X2 times upper normal limit.
4. Patients whose disease is confined to the rectum (i.e. proctitis).
5. Systemic steroid treatment at the time of enrollment (regardless of dose)
6. Prior or current treatment with biologic therapy or JAK inhibitor.
7. Patient with active infection.
8. Known immunodeficiency.
9. Known allergy to QD.
10. Pregnancy per questionnaire.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Clinical remission at 6 weeks	Six weeks after the first dose of QD	Rate of corticosteroid-free clinical remission at 6 weeks (defined as PUCAI\<10) and a decrease in PUCAI score of at least 10.

Secondary Outcome Measures

Name	Time	Method
Rate of clinical response	Three weeks after the first dose of QD	Rate of clinical response (PUCAI score decrease by 20 points or a decrease to less than 10) at week 3.
Calprotectin <250 mcg/g	Six weeks after the first dose of QD	Rate of calprotectin \<250 mcg/g at week 6.
Calprotectin decrease - week 6	Six weeks after the first dose of QD	Rate of calprotectin decrease at week 6 by \>50% compared to baseline level
Rate of clinical remission	Three weeks after the first dose of QD	Rate of clinical remission (PUCAI\<10) at week 3.
Calprotectin <100 mcg/g - week 6	Six weeks after the first dose of QD	Rate of calprotectin \<100 mcg/g at week 6.
PUCAI<10 and calprotectin <100 mcg/g	Six weeks after the first dose of QD	Rate of PUCAI\<10 and calprotectin \<100 mcg/g at week 6.
Calprotectin decrease - week 3	Three weeks after the first dose of QD	Rate of calprotectin decrease at week 3 by \>50% compared to baseline level.
Calprotectin <100 mcg/g - week 3	Three weeks after the first dose of QD	Rate of calprotectin \<100 mcg/g at week 3.
PUCAI<10 and calprotectin <100 mcg/g - week 3	Three weeks after the first dose of QD	Rate of PUCAI\<10 and calprotectin \<100 mcg/g at week 3.
Rate of QD-associated adverse events	Six weeks after the first dose of QD	Rate of QD-associated adverse events including but not limited to: PAH, elevation in liver enzymes, headaches.

Trial Locations

Locations (2)

Shaare Zedek Medical Center - The Juliet Keidan Institute of Paediatric Gastroenterology and Nutrition; 🇮🇱 Jerusalem, Israel

Schneider Children's Medical Center; 🇮🇱 Petah tikva, Israel