- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04263597
Oral Supplementation of 2'-Fucosyllactose in Allogeneic Bone Marrow Transplant Recipients
Oral Supplementation of 2'-Fucosyllactose in Allogeneic Bone Marrow Transplant Recipients to Maintain Intestinal Homeostasis
High dose chemotherapy and radiation used as preparative regimens in patients undergoing an allogeneic hematopoietic stem cell transplant (HSCT) disrupts intestinal homeostasis by damaging the intestinal epithelium and altering the intestinal microbiome. The investigators hypothesize that 2'-fucosyllactose (2FL) supplementation will be safe and tolerable and result in an increase in the relative abundance of intestinal Bifidobacteria. The investigators also hypothesize that 2FL supplementation will lead to reduction of Firmicutes and/or Proteobacteria, and improved intestinal homeostasis at day+30 as measured by lower pro-inflammatory cytokines, reduced levels of T-cell activation, lower markers of intestinal injury (fecal human DNA and plasma reg-3-alpha), increased fecal butyrate levels and ultimately lower incidence of acute GVHD and BSI at day+100.
Phase II:
The investigators hypothesize that 2FL supplementation will be safe and tolerable and result in an increase in the relative abundance of fecal short chain fatty acids such as butyrate, acetate and propionate at day+7 compared to baseline values.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This phase I/IIa study is a single center prospective study at Cincinnati Children's Hospital Medical Center (CCHMC).
This study will assess the safety and tolerability of various doses of 2FL. Eligible patients will be allocated to the following arms as determined by age at enrollment:
Arm 1: 0-5 years; Arm 2: 5.1-10 years; Arm 3: >10 years
The investigators will first enroll 5 patients of ages ≥10 years undergoing allogeneic HSCT. 2'-FL will be administered to these patients from day-7 until day+30 after HSCT at the starting dose for the ≥10 years age group. Once safety is determined the investigators will then enroll an additional 5 patients of ages 5-10 years and 5 patients of ages 0-5 years and administer 2'FL at starting doses according to their age group to children from day-7 to day+30 after HSCT. Enrollment in the 2 defined age groups (5-10 years and 0-5 years) will occur independent of each other/in parallel to establish safety. Once safety is established in these patients the investigators will proceed with the 3x3 study design dose finding portion of our study
Three patients will be enrolled in each arm at the starting dose level. Investigators will perform a dose escalation or de-escalation based on rates of dose limiting toxicities.
Phase II:
Initial 15 patients to establish safety as per the FDA have been enrolled. An additional 10 patients were enrolled and interim analyses demonstrating safety, lack of any dose limiting toxicities and a positive signal of increase in fecal acetate and propionate at day+7 compared to baseline values) were performed. The investigators will enroll approximately 45 additional patients to test efficacy of 2FL supplementation in children and young adult allogeneic HSCT patients with a goal to reduce intestinal inflammation and improve post HSCT outcomes such as acute GVHD and bloodstream infections.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Celeste Dourson
- Phone Number: (513) 636-7679
- Email: Celeste.Dourson@cchmc.org
Study Locations
-
-
Ohio
-
Cincinnati, Ohio, United States, 45229
- Recruiting
- Cincinnati Children's Hospital
-
Contact:
- Celeste Dourson
- Email: Celeste.Dourson@cchmc.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Be scheduled for allogeneic stem cell transplant
- All ages and underlying diagnoses, preparative regimens, stem cell sources and acute GVHD prophylaxes
Exclusion Criteria:
- Unable to take anything orally or enterally (i.e. intestinal failure)
- Actively breastfeeding infants
- Recent (within the week prior to enrollment) GI infection
- Patients receiving anti-diarrheal medications such as loperamide
- Patients who have received probiotics or prebiotics during the previous month
- Patients who have had any type of gut damage within the past 3 months such as previous bowel perforations, previous episode of Grade 4 neutropenic colitis or typhlitis
- Patients with inflammatory bowel disease, short bowel syndrome, and patients with a history of bowel resections
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 2'-fucosyllactose for ages 0-5 years
Dose for ages 0-5 years: 2.5 g/day;
|
2FL powder will be provided to participants randomized to receive 2FL in packets.
They will be instructed to drink this daily by adding the required amount to food or drink.
It may also be mixed in standard feeds or mixed with water and administered by enteral tube, whenever applicable.
Other Names:
|
Experimental: 2'-fucosyllactose for ages 5.1-10 years
Dose for ages 5.1-10 years: 5 g/day;
|
2FL powder will be provided to participants randomized to receive 2FL in packets.
They will be instructed to drink this daily by adding the required amount to food or drink.
It may also be mixed in standard feeds or mixed with water and administered by enteral tube, whenever applicable.
Other Names:
|
Experimental: 2'-fucosyllactose for ages >10 years
Dose for ages >10 years: 10 g/day;
|
2FL powder will be provided to participants randomized to receive 2FL in packets.
They will be instructed to drink this daily by adding the required amount to food or drink.
It may also be mixed in standard feeds or mixed with water and administered by enteral tube, whenever applicable.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of bloodstream infections
Time Frame: Day+100 after transplant
|
Number of bloodstream infections in patients on 2FL
|
Day+100 after transplant
|
Number of patients able to take 2FL
Time Frame: 1 week prior to start of chemotherapy until day+30 after transplant
|
6 of 10 patients receiving 2FL able to take 80% of their planned doses
|
1 week prior to start of chemotherapy until day+30 after transplant
|
Incidence of mucosal barrier injury laboratory-confirmed bloodstream infection (MBI-LCBI)
Time Frame: Day+ 100 after transplant
|
Incidence of MBI-LCBI in patients enrolled in phase II of the study
|
Day+ 100 after transplant
|
Incidence of graft versus host disease (GVHD)
Time Frame: Day+ 100 after transplant
|
Incidence of GVHD in patients enrolled in phase II of the study
|
Day+ 100 after transplant
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relative abundance of fecal Bifidobacteria at day+30 compared to baseline by >/=10%
Time Frame: Day+30 after transplant
|
Change in relative abundance of fecal Bifidobacteria at day+30 compared to baseline by >/=10%
|
Day+30 after transplant
|
Relative abundance of fecal Firmicutes and Proteobacteria at day+30 compared to baseline for patients on 2FL
Time Frame: Day+30 after transplant
|
Change in relative abundance of fecal Firmicutes and Proteobacteria at day+30 compared to baseline for patients on 2FL
|
Day+30 after transplant
|
Incidence of acute GVHD
Time Frame: Day+100 after transplant
|
Incidence of acute GVHD in patients on 2FL
|
Day+100 after transplant
|
Incidence of bloodstream infections
Time Frame: Day+100 after transplant
|
Incidence of bloodstream infections in patients on 2FL
|
Day+100 after transplant
|
Increase in fecal butyrate/acetate/propionate levels
Time Frame: Day+ 7 after transplant
|
Increase in fecal butyrate/acetate/propionate levels from baseline at day+ 7 in patients enrolled in phase II of the study
|
Day+ 7 after transplant
|
Collaborators and Investigators
Investigators
- Principal Investigator: Pooja Khandelwal, MD, Children's Hospital Medical Center, Cincinnati
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 2020-0008
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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