Clinical trial NCT03782272: Safety, Acceptability, and Feasibility of Enterade®
Official title: Safety, Acceptability, and Feasibility of Enterade® in Children at Risk for Environmental Enteric Dysfunction in Kakamega County, Kenya
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Stunting
Environmental Enteric Dysfunction
Lead sponsor: PATH
Sponsor class: OTHER
Collaborators: name: Maseno University
name: Kakamega County General Teaching & Referral Hospital
First posted: 2018-12-20
Enrollment: 12
Sex: ALL
Minimum age (years): 12
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: OTHER

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.

Eligibility criteria: 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 exclusion criteria for either category):

Child:

1. Has any sign of acute illness, including but not limited to fever, cough, and diarrhea.
2. Is wasted (weight for length z-score \< -2 or mid-upper arm circumference \[MUAC\] \< 12.4 cm) or has pitting edema.
3. Is exclusively breastfed.
4. Is seeking medical attention at the health facility other than for routine, preventative care (e.g., immunization visit, vitamin supplementation).
5. 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).
6. 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).
7. Participating in any other clinical trials.
8. 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).
9. Cannot give the necessary biological (blood) sample.

Caregiver:

Reports diarrhea in the household in the prior 7 days.

Primary outcomes:
measure: Frequency of Adverse Events or Serious Adverse Events
timeFrame: 0-21 days
measure: Volume of Daily Consumption of Study Product
timeFrame: 0-14 days
Secondary outcomes:
Other outcomes:
measure: Exploratory - Metabolism: Plasma Concentration of Acylcarnitines
timeFrame: Day 0 and Day 15
measure: Exploratory - Gut Damage: Plasma Concentration of Intestinal Fatty Acid-binding Protein [I-FABP]
timeFrame: Day 0 and Day 15
measure: Exploratory - Microbial Translocation: Plasma Concentration of Soluble CD14 [sCD14]
timeFrame: Day 0 and Day 15
measure: Exploratory - Gut Repair: Plasma Concentration of Glucagon-like Peptide 2 [GLP-2]
timeFrame: Day 0 and Day 15
measure: Exploratory - Growth Hormone Axis: Plasma Concentration of Insulin-like Growth Factor 1 [IGF-1]
timeFrame: Day 0 and Day 15
measure: Exploratory - Growth Hormone Axis: Plasma Concentration of Fibroblast Growth Factor 21 [FGF21]
timeFrame: Day 0 and Day 15
measure: Exploratory - Systemic Inflammation: Plasma Concentration of Alpha-1-acid Glycoprotein [AGP]
timeFrame: Day 0 and Day 15
measure: Exploratory - Systemic Inflammation:Plasma Concentration of C-reactive Protein [CRP]
timeFrame: Day 0 and Day 15
measure: Exploratory - Micronutrient Status: Plasma Concentration of Ferritin
timeFrame: Day 0 and Day 15
measure: Exploratory - Micronutrient Status: Plasma Concentration of Soluble Transferrin Receptor [sTfR]
timeFrame: Day 0 and Day 15
measure: Exploratory - Micronutrient Status: Plasma Concentration of Retinol-binding Protein 4 [RBP4]
timeFrame: Day 0 and Day 15
measure: Exploratory - Micronutrient Status: Plasma Concentration of Thyroglobulin
timeFrame: Day 0 and Day 15
Locations:
city: Kakamega
country: Kenya
facility: Kakamega County General Teaching and Referral Hospital
Study officials:
References: