Back to resultsSafety, Acceptability, and Feasibility of Enterade® (SAFE)
Primary Purpose
Stunting, Environmental Enteric Dysfunction
Status
Terminated
Phase
Not Applicable
Locations
Kenya
Study Type
Interventional
Intervention
Enterade
Placebo
Sponsored by
About this trial
This is an interventional other trial for Stunting
Eligibility Criteria
Inclusion Criteria:
Pediatric and caregiver pairs (must meet inclusion criteria for both categories):
Child:
- Is between 12 and 24 months of age.
- LAZ between -3 and -1 standard deviations (SD).
- At least one week post routine immunization, healthy child visit, or vitamin A supplementation visit at the study site.
- Has a parent or legally acceptable representative willing and able to provide informed consent.
- No plans for travel outside of the community for the duration of the study.
Caregiver of child:
- Is a parent or legally accepted representative of a child eligible for this study.
- Is 18 years of age or older.
- Has a working mobile phone.
- Is willing and able to provide informed consent.
- If illiterate-there is at least one literate adult living in the child's household.
Exclusion Criteria:
Pediatric and caregiver pairs (must meet none of the exclusion criteria for either category):
Child:
- Has any sign of acute illness, including but not limited to fever, cough, and diarrhea.
- Is wasted (weight for length z-score < -2 or mid-upper arm circumference [MUAC] < 12.4 cm) or has pitting edema.
- Is exclusively breastfed.
- Is seeking medical attention at the health facility other than for routine, preventative care (e.g., immunization visit, vitamin supplementation).
- Has suffered within the prior week from illnesses that might impact nutritional status (e.g., severe diarrhea or pneumonia; vomiting; persistent diarrhea; cleft lip or palate; blindness; tuberculosis; jaundice; renal or cardiac disease; cerebral palsy; known metabolic disorders; and chromosomal disorders, including trisomy 21).
- Medical history of chronic health condition (i.e., HIV, hepatitis B or C, end stage renal disease, severe liver disease-absence of a diagnosis is sufficient).
- Participating in any other clinical trials.
- Recent (prior 2 weeks) use of antibiotics or any other medical treatments (including oral re-hydration solution), but not including vaccines or vitamin/mineral supplementation).
- Cannot give the necessary biological (blood) sample.
Caregiver:
Reports diarrhea in the household in the prior 7 days.
Sites / Locations
- Kakamega County General Teaching and Referral Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
AA-ORS
Placebo
Arm Description
Those receiving enterade oral re-hydration solution with amino acids
Those receiving placebo solution without amino acids or rehydration salts
Outcomes
Primary Outcome Measures
Frequency of Adverse Events or Serious Adverse Events
Frequency of adverse events or serious adverse events in study product and placebo arms through 21 days of follow-up as assessed by physical/clinical examination.
Volume of Daily Consumption of Study Product
Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.
Secondary Outcome Measures
Full Information
NCT ID
NCT03782272
First Posted
May 16, 2018
Last Updated
February 2, 2021
Sponsor
PATH
Collaborators
Maseno University, Kakamega County General Teaching & Referral Hospital
1. Study Identification
Unique Protocol Identification Number
NCT03782272
Brief Title
Safety, Acceptability, and Feasibility of Enterade®
Acronym
SAFE
Official Title
Safety, Acceptability, and Feasibility of Enterade® in Children at Risk for Environmental Enteric Dysfunction in Kakamega County, Kenya
Study Type
Interventional
2. Study Status
Record Verification Date
July 2020
Overall Recruitment Status
Terminated
Why Stopped
Study product bottles were found on site that did not meet product specifications. This prompted a 6-week safety review of participants (no study-related findings) and resulted in the study's termination.
Study Start Date
February 26, 2019 (Actual)
Primary Completion Date
March 20, 2019 (Actual)
Study Completion Date
June 30, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
Maseno University, Kakamega County General Teaching & Referral Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This is a randomized, double-blinded, placebo-controlled pilot study to determine the safety, acceptability, and feasible pediatric dosage/tolerability of enterade® solution, an amino acid-based oral rehydration solution (AA-ORS), for potential use in the management of environmental enteric dysfunction (EED) among children aged 12-24 months in Kakamega County, Kenya.
Primary objectives:
To determine the safety of a 2-week course of AA-ORS among children with length-for-age Z-scores (LAZ) between -1 and -3.
To determine the feasibility and best tolerated dose of AA-ORS among children with LAZ between -3 and -1.
Secondary objectives:
To determine the perceptions among caregivers on the acceptability of AA-ORS as a potential intervention for EED. (Qualitative)
Exploratory objectives:
To determine the impact of AA-ORS on markers of metabolism, gut dysfunction, systemic inflammation, and micronutrient status among children with LAZ between -3 and - 1.
Qualitative results will not be reported on ClinicalTrials.gov.
Detailed Description
Environmental enteric dysfunction (EED) is an intestinal disorder common among people living in low-resource settings (LRS), which in children has been associated with increased risk of growth stunting, reduced cognitive development, and reduced oral vaccine responsiveness. An effective EED therapeutic would offer an opportunity to improve child growth and development in LRS. One promising intervention, enterade® (an amino acid-based oral rehydration solution [AA-ORS]), is a medical food product already sold in the United States. It consists of oral rehydration salts and a proprietary blend of amino acids designed to restore gut function, improve nutrient and electrolyte absorption, and improve barrier integrity. There is evidence that this AA-ORS reduces inflammation and promotes healing of damaged intestinal epithelium in murine models of intestinal damage (irradiated gut), and it may provide benefit to pediatric EED patients. Supplementation of amino acids may lessen or improve intestinal injury related to enteric illnesses commonly experienced in settings of poor hygiene and sanitation infrastructure. The results from this exploratory mixed-methods study could have broad implications for possible future studies among pediatric patients with intestinal injury resulting from EED and future product development and program strategies for EED interventions.
The study was terminated prematurely after study product was found on site that did not meet product specifications. Enrollment and all study product dosing was halted; previously enrolled participants were followed through planned study visits and assessments. An additional 6-week safety follow-up period was added to study procedures. No study-related adverse events were reported during per-protocol activities or from the additional 6-week follow-up.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Stunting, Environmental Enteric Dysfunction
7. Study Design
Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
This is a mixed-methods pilot study to assess the safety, acceptability, and feasible dosage of AA-ORS among children with mild to moderate stunting (LAZ between -1 and -3) who are at risk for EED and to assess the acceptability of this fluid supplementation for their caregivers. During the main study, up to 66 child participants will be randomized to receive 14 days of AA-ORS or placebo solution daily, dosing of up to 237 ml over a 3-hour period. Study staff and participants will be blinded to the study product allocation. Caregivers will store and return unused study product. Data collection methods to include direct observation of product consumption, structured surveys with caregivers, average daily volume consumed, and measurement of plasma/serum markers of metabolism, gut dysfunction, systemic inflammation, and micro-nutrient status pre- and post-administration of product.
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
AA-ORS
Arm Type
Experimental
Arm Description
Those receiving enterade oral re-hydration solution with amino acids
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Those receiving placebo solution without amino acids or rehydration salts
Intervention Type
Dietary Supplement
Intervention Name(s)
Enterade
Intervention Description
enterade® (an amino acid-based oral rehydration solution [AA-ORS]) is a medical food product that consists of oral rehydration salts, natural flavor, steviol (sweetener), purified water, and a blend of amino acids that drive the uptake of water and electrolytes.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Primary Outcome Measure Information:
Title
Frequency of Adverse Events or Serious Adverse Events
Description
Frequency of adverse events or serious adverse events in study product and placebo arms through 21 days of follow-up as assessed by physical/clinical examination.
Time Frame
0-21 days
Title
Volume of Daily Consumption of Study Product
Description
Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.
Time Frame
0-14 days
Other Pre-specified Outcome Measures:
Title
Exploratory - Metabolism: Plasma Concentration of Acylcarnitines
Description
Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]
Description
Plasma concentration of intestinal fatty acid-binding protein [I-FABP] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]
Description
Plasma concentration of soluble CD14 [sCD14] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]
Description
Plasma concentration of glucagon-like peptide 2 [GLP-2] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]
Description
Plasma concentration of insulin-like growth factor 1 [IGF-1] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]
Description
Plasma concentration of fibroblast growth factor 21 [FGF21] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]
Description
Plasma concentration of alpha-1-acid glycoprotein [AGP] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]
Description
Plasma concentration of c-reactive protein [CRP] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Micronutrient Status: Plasma Concentration of Ferritin
Description
Plasma concentration of ferritin assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]
Description
Plasma concentration of soluble transferrin receptor [sTfR] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]
Description
Plasma concentration of retinol-binding protein 4 [RBP4] assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
Title
Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin
Description
Plasma concentration of thyroglobulin assessed at baseline and day 15 of follow-up.
Time Frame
Day 0 and Day 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
24 Months
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Pediatric and caregiver pairs (must meet inclusion criteria for both categories):
Child:
Is between 12 and 24 months of age.
LAZ between -3 and -1 standard deviations (SD).
At least one week post routine immunization, healthy child visit, or vitamin A supplementation visit at the study site.
Has a parent or legally acceptable representative willing and able to provide informed consent.
No plans for travel outside of the community for the duration of the study.
Caregiver of child:
Is a parent or legally accepted representative of a child eligible for this study.
Is 18 years of age or older.
Has a working mobile phone.
Is willing and able to provide informed consent.
If illiterate-there is at least one literate adult living in the child's household.
Exclusion Criteria:
Pediatric and caregiver pairs (must meet none of the exclusion criteria for either category):
Child:
Has any sign of acute illness, including but not limited to fever, cough, and diarrhea.
Is wasted (weight for length z-score < -2 or mid-upper arm circumference [MUAC] < 12.4 cm) or has pitting edema.
Is exclusively breastfed.
Is seeking medical attention at the health facility other than for routine, preventative care (e.g., immunization visit, vitamin supplementation).
Has suffered within the prior week from illnesses that might impact nutritional status (e.g., severe diarrhea or pneumonia; vomiting; persistent diarrhea; cleft lip or palate; blindness; tuberculosis; jaundice; renal or cardiac disease; cerebral palsy; known metabolic disorders; and chromosomal disorders, including trisomy 21).
Medical history of chronic health condition (i.e., HIV, hepatitis B or C, end stage renal disease, severe liver disease-absence of a diagnosis is sufficient).
Participating in any other clinical trials.
Recent (prior 2 weeks) use of antibiotics or any other medical treatments (including oral re-hydration solution), but not including vaccines or vitamin/mineral supplementation).
Cannot give the necessary biological (blood) sample.
Caregiver:
Reports diarrhea in the household in the prior 7 days.
Facility Information:
Facility Name
Kakamega County General Teaching and Referral Hospital
City
Kakamega
Country
Kenya
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety, Acceptability, and Feasibility of Enterade®
We'll reach out to this number within 24 hrs