Pilot and Feasibility Study of 2'-FL as a Dietary Supplement in IBD Patients Receiving Stable Maintenance Anti-TNF Therapy

Study Overview
=================
Brief Summary
-----------------
Randomized, placebo-controlled dose-ranging study of 2'-FL in IBD, Crohn's Disease (CD) and ulcerative colitis (UC). The overarching hypothesis is that 2'-FL supplementation in IBD will be safe and well tolerated, while increasing fecal Bifidobacterium abundance and butyrate in a dose dependent manner. The investigators will test 1, 5, or 10 gm 2'-FL compared to 2 gm dextrose placebo as a daily dietary supplement in pediatric and young adult IBD participants in stable remission receiving infliximab, adalimumab, or infliximab-dyyb biosimilar anti-TNF therapy.

Official Title
-----------------
Pilot and Feasibility Study of 2'-FL as a Dietary Supplement in Pediatric and Young Adult IBD Patients Receiving Stable Maintenance Anti-TNF Therapy

Conditions
-----------------
Inflammatory Bowel Diseases, Crohn Disease, Ulcerative Colitis

Intervention / Treatment
-----------------
* Drug: 2'-Fucosyllactose
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Provision of signed and dated informed consent form Stated willingness to comply with all study procedures and availability for the duration of the study Male or female, aged 11 - 25 Diagnosed with Crohns Disease or Ulcerative Colitis Disease is in remission Adult CD (age 18-25): CDAI score < 150 Pediatric CD (age 11-17): wPCDAI < 12.5 Adult UC (age 18-25): Modified Mayo sub-scores: stool frequency sub-score=0, rectal bleeding sub-score=0 Pediatric UC (age 11-17): PUCAI score < 10 Not receiving corticosteroids Receiving a stable anti-TNF maintenance dose of adalimumab, infliximab, or the biosimilar infliximab-dyyb for 12 weeks prior to enrollment. A stable infliximab or infliximab-dyyb dose may range from 5 mg/kg every 8 weeks to 10 mg/kg every 4 weeks. A stable adalimumab dose may range from 20 mg every 2 weeks to 40 mg every 7 days. While therapeutic drug monitoring will not be required for inclusion, all drug and anti-drug antibody levels obtained for clinical indications within six months prior to enrollment, and from the screening visit through week 20, will be recorded. If receiving mesalamine, mercaptopurine, azathioprine, or methotrexate, must be on a stable dose for at least 12 weeks prior to enrollment. Agreement to not make any major dietary changes throughout study duration. This would include changing usual diet to a vegan diet, Specific Carbohydrate Diet (SCD), or exclusive enteral nutrition (EEN) diet. We will include CD patients who have had one ileo-colic resection, as long as the resection did not include more of the colon than the cecum and ascending colon. CD patients may be enrolled if at least six months post-surgery. Exclusion Criteria: Experienced active IBD clinical disease during the previous six months as determined by the Principal Investigator. Use of any of the following medications during the previous month: antibiotics, probiotics or prebiotics Diagnosis of celiac disease, diabetes or other co-morbidity that is determined by the PI as being exclusionary Treatment with another investigational drug or other intervention within 4 weeks Treatment with other biologic medication for IBD within prior 12 weeks Problem with lactose breakdown Currently pregnant or breast feeding We will exclude CD patients with more than one IBD related surgery, or those with a sub-total colectomy. We will exclude UC patients with colectomy or IBD related surgery. We will not allow concomitant use of anti-diarrheal medications.

Ages Eligible for Study
-----------------
Minimum Age: 11 Years
Maximum Age: 25 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 2'-Fucosyllactose<br>Phase I: 36 young adult participants aged 18-25 years. Group 1: 1 gm per day n=12 (6UC/6CD) Group 2: 5 gm per day n=12 (6UC/6CD) Group 3: 10 gm per day n=12 (6UC/6CD) Phase II (post Phase I interim safety analysis): 120 participants aged 11-25 years Group 1: 1 gm per day n=40 (20UC/20CD) Group 2: 5 gm per day n=40 (20UC/20CD) Group 3: 10 gm per day n=40 (20UC/20CD) | Drug: 2'-Fucosyllactose<br>* Human milk oligosaccharide prebiotic dietary supplement<br>* Other names: 2'-FL;|
| Placebo Comparator: Placebo<br>Phase I: 20 young adult participants age 18-25 years dosed at 2 gm placebo per day. (10UC/10CD) Phase II (post Phase I interim safety analysis): 40 participants age 11-25 years dosed at 2 gm placebo per day. (20UC/20CD) | Other: Placebo<br>* Dextrose<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Gastrointestinal Symptom Rating Scale (GSRS) in participants who receive 2'-fucosyllactose (2'FL) or dextrose placebo | Measured by the Gastrointestinal Symptom Rating Scale (GSRS). The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire for patients with GI symptoms. Patients are asked to numerically score their subjective symptoms on a scale of 1-7 (1=no discomfort up to 7=severe discomfort). The sum of the scores for all 15 items is regarded as the GSRS total score | 20 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean fecal Bifidobacterium abundance in participants who receive 2'-fucosyllactose (2'FL) or dextrose placebo | Measured by fecal DNA 16S ribosomal sequencing | 20 weeks |