Safety, Acceptability, and Feasibility of Enterade®

Safety, Acceptability, and Feasibility of Enterade® in Children at Risk for Environmental Enteric Dysfunction in Kakamega County, Kenya

Status

Terminated

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03782272

Acronym

SAFE

Enrollment

Registered

2018-12-20

Start date

2019-02-26

Completion date

2020-06-30

Last updated

2021-02-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Stunting, Environmental Enteric Dysfunction

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: 1. 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. 2. To determine the feasibility and best tolerated dose of AA-ORS among children with LAZ between -3 and -1. Secondary objectives: 3. To determine the perceptions among caregivers on the acceptability of AA-ORS as a potential intervention for EED. (Qualitative) Exploratory objectives: 4. 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.

Interventions

DIETARY_SUPPLEMENTEnterade

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.

DIETARY_SUPPLEMENTPlacebo

a placebo solution containing natural flavor, steviol (sweetener), and purified water.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

OTHER

Masking

TRIPLE (Subject, Caregiver, Investigator)

Intervention 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.

Eligibility

Sex/Gender

ALL

Age

12 Months to 24 Months

Healthy volunteers

Yes

Inclusion criteria

Pediatric and caregiver pairs (must meet inclusion criteria for both categories): Child: 1. Is between 12 and 24 months of age. 2. LAZ between -3 and -1 standard deviations (SD). 3. At least one week post routine immunization, healthy child visit, or vitamin A supplementation visit at the study site. 4. Has a parent or legally acceptable representative willing and able to provide informed consent. 5. No plans for travel outside of the community for the duration of the study. Caregiver of child: 1. Is a parent or legally accepted representative of a child eligible for this study. 2. Is 18 years of age or older. 3. Has a working mobile phone. 4. Is willing and able to provide informed consent. 5. 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

Design outcomes

Primary

Measure	Time frame	Description
Frequency of Adverse Events or Serious Adverse Events	0-21 days	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	0-14 days	Total, average, and trends in daily study product volume consumed measured as milliliters per day through the 14 days of dosing.

Other

Measure	Time frame	Description
Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]	Day 0 and Day 15	Plasma concentration of soluble CD14 \[sCD14\] assessed at baseline and day 15 of follow-up.
Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]	Day 0 and Day 15	Plasma concentration of glucagon-like peptide 2 \[GLP-2\] assessed at baseline and day 15 of follow-up.
Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]	Day 0 and Day 15	Plasma concentration of insulin-like growth factor 1 \[IGF-1\] assessed at baseline and day 15 of follow-up.
Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]	Day 0 and Day 15	Plasma concentration of fibroblast growth factor 21 \[FGF21\] assessed at baseline and day 15 of follow-up.
Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]	Day 0 and Day 15	Plasma concentration of alpha-1-acid glycoprotein \[AGP\] assessed at baseline and day 15 of follow-up.
Exploratory - Metabolism: Plasma Concentration of Acylcarnitines	Day 0 and Day 15	Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.
Exploratory - Micronutrient Status: Plasma Concentration of Ferritin	Day 0 and Day 15	Plasma concentration of ferritin assessed at baseline and day 15 of follow-up.
Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]	Day 0 and Day 15	Plasma concentration of soluble transferrin receptor \[sTfR\] assessed at baseline and day 15 of follow-up.
Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]	Day 0 and Day 15	Plasma concentration of retinol-binding protein 4 \[RBP4\] assessed at baseline and day 15 of follow-up.
Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin	Day 0 and Day 15	Plasma concentration of thyroglobulin assessed at baseline and day 15 of follow-up.
Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]	Day 0 and Day 15	Plasma concentration of c-reactive protein \[CRP\] assessed at baseline and day 15 of follow-up.
Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]	Day 0 and Day 15	Plasma concentration of intestinal fatty acid-binding protein \[I-FABP\] assessed at baseline and day 15 of follow-up.

Countries

Kenya

Participant flow

Participants by arm

Arm	Count
AA-ORS Those receiving enterade oral re-hydration solution with amino acids Enterade: 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.	6
Placebo Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.	6
Total	12

Baseline characteristics

Characteristic	Placebo	Total	AA-ORS
Age, Continuous	16 months	18 months	18 months
Length	75.3 cm	78 cm	78.95 cm
Mid-upper arm circumference (MUAC)	141 mm	145 mm	150.5 mm
Race and Ethnicity Not Collected	—	0 Participants	—
Region of Enrollment Kenya	6 participants	12 participants	6 participants
Sex: Female, Male Female	3 Participants	4 Participants	1 Participants
Sex: Female, Male Male	3 Participants	8 Participants	5 Participants
Weight	9.03 kg	10.0 kg	10.55 kg

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 6	0 / 6
other Total, other adverse events	1 / 6	0 / 6
serious Total, serious adverse events	0 / 6	0 / 6

Outcome results

Primary

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.

Time frame: 0-21 days

Population: This is the intention-to-treat population with all participants randomized and received at least one dose.

Arm	Measure	Value (COUNT_OF_PARTICIPANTS)
AA-ORS	Frequency of Adverse Events or Serious Adverse Events	1 Participants
Placebo	Frequency of Adverse Events or Serious Adverse Events	0 Participants

Primary

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.

Time frame: 0-14 days

Population: Intention-to-treat

Arm	Measure	Value (MEDIAN)
AA-ORS	Volume of Daily Consumption of Study Product	212.5 ml

Other Pre-specified

Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]

Plasma concentration of fibroblast growth factor 21 \[FGF21\] assessed at baseline and day 15 of follow-up.

Time frame: Day 0 and Day 15