SAFE: Safety, Acceptability, and Feasibility of Enterade®

• Sponsor: PATH (Other)
• Overall Status: Terminated
• CT.gov ID: NCT03782272
• Collaborator: Maseno University (Other), Kakamega County General Teaching & Referral Hospital (Other)
• Enrollment: 12
• Location: 1
• Arms: 2
• Actual Duration (Months): 16.1
• Patients Per Site Per Month: 0.7

Study Details

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:

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:

1. To determine the perceptions among caregivers on the acceptability of AA-ORS as a potential intervention for EED. (Qualitative)

Exploratory objectives:

1. 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.

Condition or Disease	Intervention/Treatment	Phase
Stunting; Environmental Enteric Dysfunction	Dietary Supplement: Enterade; Dietary Supplement: Placebo	N/A

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.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: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Other
• Official Title: Safety, Acceptability, and Feasibility of Enterade® in Children at Risk for Environmental Enteric Dysfunction in Kakamega County, Kenya
• Actual Study Start Date: Feb 26, 2019
• Actual Primary Completion Date: Mar 20, 2019
• Actual Study Completion Date: Jun 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: AA-ORS Those receiving enterade oral re-hydration solution with amino acids	Dietary Supplement: 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.
Placebo Comparator: Placebo Those receiving placebo solution without amino acids or rehydration salts	Dietary Supplement: Placebo; a placebo solution containing natural flavor, steviol (sweetener), and purified water.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. Exploratory - Metabolism: Plasma Concentration of Acylcarnitines [Day 0 and Day 15]

   Plasma concentration of acylcarnitines assessed at baseline and day 15 of follow-up.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Months to 24 Months
• Sexes Eligible for Study: All
• Accepts 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 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kakamega County General Teaching and Referral Hospital	Kakamega		Kenya

Sponsors and Collaborators

• PATH
• Maseno University
• Kakamega County General Teaching & Referral Hospital

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 28, 2018

More Information

Publications

None provided.

• Responsible Party: PATH
• ClinicalTrials.gov Identifier: NCT03782272
• Other Study ID Numbers: 1191395-1
• First Posted: Dec 20, 2018
• Last Update Posted: Feb 4, 2021
• Last Verified: Jul 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Growth Disorders

Study Results

Participant Flow

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Period Title: Overall Study
STARTED	6	6
COMPLETED	6	6
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	AA-ORS	Placebo	Total
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.	Total of all reporting groups
Overall Participants	6	6	12
Age (months) [Median (Full Range) ]
Median (Full Range) [months]	18	16	18
Sex: Female, Male (Count of Participants)
Female	1 16.7%	3 50%	4 33.3%
Male	5 83.3%	3 50%	8 66.7%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
Kenya	6 100%	6 100%	12 100%
Length (cm) [Median (Full Range) ]
Median (Full Range) [cm]	78.95	75.3	78
Weight (kg) [Median (Full Range) ]
Median (Full Range) [kg]	10.55	9.03	10.0
Mid-upper arm circumference (MUAC) (mm) [Median (Full Range) ]
Median (Full Range) [mm]	150.5	141	145

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	6	6
Count of Participants [Participants]	1 16.7%	0 0%

2. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

Intention-to-treat

Arm/Group Title	Pooled Arms
Arm/Group Description	Due to study termination, insufficient data was collected for per-arm analysis. Only 2 participants completed the study per-protocol with a total of 12 having at least one dose of study product (target sample size was 66). Both AA-ORS and placebo arms data are pooled together.
Measure Participants	12
Median (Full Range) [ml]	212.5

3. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

4. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

5. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

6. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

7. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

8. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

9. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

10. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

11. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

12. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

13. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

14. Other Pre-specified Outcome

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

Outcome Measure Data

Analysis Population Description

Due to study termination, exploratory analyses were not conducted on specimens collected.

Arm/Group Title	AA-ORS	Placebo
Arm/Group Description	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.	Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
Measure Participants	0	0

Adverse Events

Time Frame	21 days
Arm/Group Title	AA-ORS		Placebo
Arm/Group Description	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.		Those receiving placebo solution without amino acids or rehydration salts Placebo: a placebo solution containing natural flavor, steviol (sweetener), and purified water.
All Cause Mortality
	AA-ORS		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Serious Adverse Events
	AA-ORS		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/6 (0%)		0/6 (0%)
Other (Not Including Serious) Adverse Events
	AA-ORS		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/6 (16.7%)		0/6 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	1/6 (16.7%)	1	0/6 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.