Hematopoietic Organs; Disorder
Conditions
Keywords
Probiotics, Hematopoietic Stem Cell Transplantation, Pediatrics
Brief summary
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.
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.
Interventions
DRUGLactobacillus 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)
Sponsors
Johns Hopkins All Children's Hospital
Nemours Children's Clinic
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Lactobacillus Plantarum Bacteremia Infections | 36 days (day -7 to +28 of HSCT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adherence With the Prescribed Dose, Measured as the Percentage of Prescribed Probiotic Doses | 22 days (day -7 to +14 of HSCT) | 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). |
| Number of Non-lactobacillus Infections | 36 days (day -7 to +28 of HSCT) | To determine incidence of bacteremia in HSCT patients who have been administered lactobacillus plantarum. |
| Number of Acute Graft Versus Host Disease (GVHD) Events in HSCT Patients Who Have Been Administered Lactobacillus Plantarum | Up to Day +100 of HSCT | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
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. | 31 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | < 50% adherence to probiotic | 1 |
Baseline characteristics
| Characteristic | Lactobacillus Plantarum |
|---|---|
| Age, Continuous | 7.8 years STANDARD_DEVIATION 4.7 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 17 Participants |
| Region of Enrollment United States | 31 participants |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 30 |
| serious Total, serious adverse events | 0 / 30 |
Outcome results
Primary
Number of Lactobacillus Plantarum Bacteremia Infections
Time frame: 36 days (day -7 to +28 of HSCT)
Population: Children and adolescents undergoing hematopoietic stem cell transplantation (HSCT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Plantarum | Number of Lactobacillus Plantarum Bacteremia Infections | 0 Number of infections |
Secondary
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).
Time frame: 22 days (day -7 to +14 of HSCT)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Lactobacillus Plantarum | Adherence With the Prescribed Dose, Measured as the Percentage of Prescribed Probiotic Doses | 97 percentage of prescribed doses |
Secondary
Number of Acute Graft Versus Host Disease (GVHD) Events in HSCT Patients Who Have Been Administered Lactobacillus Plantarum
Time frame: Up to Day +100 of HSCT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Plantarum | Number of Acute Graft Versus Host Disease (GVHD) Events in HSCT Patients Who Have Been Administered Lactobacillus Plantarum | 9 Number of GVHD events |
Secondary
Number of Non-lactobacillus Infections
To determine incidence of bacteremia in HSCT patients who have been administered lactobacillus plantarum.
Time frame: 36 days (day -7 to +28 of HSCT)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Lactobacillus Plantarum | Number of Non-lactobacillus Infections | 6 Number of non-lactobacillus infections |