Probiotic Use in Children Undergoing Hematopoietic Stem Cell Transplantation (HSCT)

A Limited Institution Pilot Trial Evaluating the Safety of Administering the Probiotic, Lactobacillus Plantarum, to Children and Adolescents Undergoing Allogenic Hematopoietic Stem Cell Transplantation (HSCT) - A Pilot Study

Primary Objective:

1. To evaluate the safety of orally administered Lactobacillus plantarum strains 299 and 299v, a probiotic, in patients undergoing allogeneic myeloablative HSCT, as measured by incidence of Lactobacillus plantarum bacteremia.

Secondary Objectives:

1. To investigate the feasibility of administering Lactobacillus plantarum 299 and 299v to children and adolescents undergoing HSCT.
2. To describe the overall incidence of bacteremia in HSCT patients who have been administered Lactobacillus plantarum.
3. To describe the overall incidence of acute graft versus host disease (GVHD) in HSCT patients who have been administered Lactobacillus plantarum.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Organs; Disorder
• Intervention / Treatment: Drug: Lactobacillus plantarum strains 299 and 299v

Detailed Description

Myeloablative regimens are the backbone of hematopoietic stem cell transplantation (HSCT) and are associated with prolonged periods of cachexia/anorexia, nausea/vomiting, mucositis, and compromised gut integrity (CGI). The toxicities associated with HSCT often lead to prolonged periods of poor oral intake and may result in overt malnutrition. CGI decreases oral tolerance to foods, reduces Quality of Life (QOL) and functional status, delays the transition from the hospital to home setting, and increases the risk of the development of gut-derived infections. Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and upon administration confer a benefit to the host. Clinical trials in adults receiving organ transplants have found probiotics decrease the incidence of infection, the duration of antibiotic use, the incidence of multiorgan failure and systemic inflammation. Children and adolescents undergoing HSCT, experience similar clinical challenges suggesting probiotics may have a therapeutic value in the setting of HSCT. This study is to evaluate the safety and feasibility of administering probiotics to children and adolescents undergoing HSCT.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Saint Petersburg, Florida, United States, 33701
      • All Children's Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia Universtiy Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• All patients undergoing myeloablative allogeneic HSCT will be eligible. The source of stem cells can be from bone marrow, umbilical cord blood or cytokine mobilized peripheral blood. Donor can be human leukocyte antigen (HLA) matched sibling or parent, a related donor mismatched for a single HLA locus (class I or II), unrelated marrow or peripheral blood stem cell donor, or unrelated cord blood at least 4/6 antigen match (Class 1 or II).
• Patients of either gender and between 2 and 17.99 years of age
• Patients receiving any type of GVHD prophylaxis are eligible.

Exclusion Criteria:

• Patients who have self-prescribed probiotics within 3 months of starting the conditioning regimen for stem cell transplant (consumption of yogurt products is allowed).
• Patients with known allergy to oats.
• Patients who have had any type of gut damage within the past three months; such as, previous bowel perforations; previous episode of Grade 4 neutropenic colitis or typhlitis.
• Patients with inflammatory bowel syndrome, short small bowel syndrome, Crohns Disease, Ulcerative Colitis, and patients with a history of bowel resections.
• Patients who have undergone a previous allogeneic HSCT.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lactobacillus plantarum; There is a single intervention arm in this study. Target accrual for the intervention is 30 subjects. Subjects receive supplementation with Lactobacillus plantarum strains 299 and 299v.	Drug: Lactobacillus plantarum strains 299 and 299v; Patients will receive a daily dose of Lactobacillus plantarum: 1 x10^8 CFU/kg/day. This supplement will be supplied in sachets of powder and will be mixed in water (certain water-based liquid) that is no warmer that 37o C. Colony forming units (CFU); Other Names: Probiotics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Lactobacillus Plantarum Bacteremia Infections	36 days (day -7 to +28 of HSCT)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence With the Prescribed Dose, Measured as the Percentage of Prescribed Probiotic Doses	To determine the feasibility of administration of L. plantarum 299 and 299v. The treatment is considered feasible for a patient if he/she received at least 50% of the probiotic dose (>= 11 days of treatment).	22 days (day -7 to +14 of HSCT)
Number of Non-lactobacillus Infections	To determine incidence of bacteremia in HSCT patients who have been administered lactobacillus plantarum.	36 days (day -7 to +28 of HSCT)
Number of Acute Graft Versus Host Disease (GVHD) Events in HSCT Patients Who Have Been Administered Lactobacillus Plantarum		Up to Day +100 of HSCT

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Nemours Children's Clinic; Johns Hopkins All Children's Hospital
• Investigators: Principal Investigator: Michael Neider, MD, Johns Hopkins All Children's Hospital; Principal Investigator: Elena J Ladas, PhD, RD, Columbia University

Study record dates

Study Major Dates

• Study Start: February 1, 2010
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: November 6, 2009
• First Submitted That Met QC Criteria: November 9, 2009
• First Posted (Estimate): November 10, 2009

Study Record Updates

• Last Update Posted (Actual): July 13, 2017
• Last Update Submitted That Met QC Criteria: July 11, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: Probiotics; Pediatrics; Hematopoietic Stem Cell Transplantation
• Other Study ID Numbers: AAAE0846

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No