NCT01832636

Brief Summary

Several host factors underlie the pathogenesis of the reciprocal cycle of childhood diarrhea and undernutrition in developing countries. These include intestinal inflammation, mucosal damage, and alterations in intestinal barrier function that lead to malabsorption, growth failure, and heightened susceptibility to recurrent and prolonged episodes of diarrhea. Recent studies from Northeast Brazil demonstrate the benefits of a novel alanyl-glutamine-based oral rehydration and nutrition therapy (Ala-Gln ORNT) in speeding the recovery of damaged intestinal barrier function in cell culture, animal models, patients with AIDS, and underweight children. Oral supplementation with Alanyl-Glutamine (Ala-Gln; 24g a day for 10 days) improves short-term gut integrity and weight velocity 4 months after therapy in a group of undernourished children from Northeast Brazil. Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy (IMAGINE) is a study designed to answer the following questions: 1) What is the lowest dose of Ala-Gln that improves intestinal barrier function, intestinal inflammation, and nutritional status in children at risk of underweight, wasting, or stunting? 2) What are the mechanisms by which Ala-Gln exerts these benefits?

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
112

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Oct 2013

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 12, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

April 16, 2013

Completed
6 months until next milestone

Study Start

First participant enrolled

October 1, 2013

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

August 1, 2016

Status Verified

July 1, 2016

Enrollment Period

2.2 years

First QC Date

April 12, 2013

Last Update Submit

July 28, 2016

Conditions

Keywords

L-Alanyl-L-GlutamineEnvironmental enteric dysfunctionTropical enteropathy

Outcome Measures

Primary Outcomes (1)

  • Urinary Lactulose: Mannitol Intestinal Permeability Test

    Determine the dose-and time-effect of alanyl-glutamine on intestinal barrier function recovery using the intestinal permeability test, with measurement of the percentage of urinary excretion of lactulose, mannitol and ratio of lactulose:mannitol.

    Urine Collection on Day 1, 10-13, 30-37

Secondary Outcomes (6)

  • Fecal Lactoferrin Test

    Fecal sample collected on Day 1, 10-13, 30-37

  • Fecal Cytokine Measurement

    Fecal sample collected on Day 1, 10-13

  • Anthropometry

    Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141

  • Fecal Calorimetry

    Fecal sample collected on Day 1, 10-13, 30-37

  • Metabolomic Profile of Urine

    Collected on Day 1, 10-13, 30-37

  • +1 more secondary outcomes

Study Arms (4)

Alanyl-Glutamine 3g/d

ACTIVE COMPARATOR

Alanyl-Glutamine orally 3g/day for 10 days

Dietary Supplement: Alanyl-Glutamine

Alanyl-Glutamine 6g/d

ACTIVE COMPARATOR

Alanyl-Glutamine orally 6g/day for 10 days

Dietary Supplement: Alanyl-Glutamine

Alanyl-Glutamine 12g/d

ACTIVE COMPARATOR

Alanyl-Glutamine orally 12g/d for 10 days

Dietary Supplement: Alanyl-Glutamine

Glycine 12.5g/d

PLACEBO COMPARATOR

Glycine orally 12.5 g/d for 10 days. This dose is calculated to be isonitrogenous to 12g of Alanyl-Glutamine.

Dietary Supplement: Alanyl-Glutamine

Interventions

Alanyl-GlutamineDIETARY_SUPPLEMENT

Alanyl-Glutamine and Glycine doses will be prepared immediately prior to administration by dissolving in formula, milk, or fruit juice. Administration of each dose will be directly observed by a study nurse or health agent.

Also known as: AminoStable (Ajinomoto)
Alanyl-Glutamine 12g/dAlanyl-Glutamine 3g/dAlanyl-Glutamine 6g/dGlycine 12.5g/d

Eligibility Criteria

Age2 Months - 5 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Children who are undernourished or at risk of undernutrition, with anthropometric z-scores less than or equal to -1 for one of these parameters: height-for-age, weight-for-age, or weight-for-height.
  • Children ages 2 months to 5 years old.

You may not qualify if:

  • Children who are exclusively breastfed.
  • Have participated in another intervention study in the past two years.
  • Fever greater than 38.8 ° C.
  • Use of antibiotics.
  • Systemic disease or other serious medical condition (including, but not limited to meningitis, pneumonia, tuberculosis, and chickenpox).
  • Children who are unable to ingest, retain or absorb nutritional supplements.
  • Children whose families plan to move from the study area within the next 6 months.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Universidade Federal do Ceara

Fortaleza, Ceará, Brazil

Location

Related Publications (2)

  • Lima NL, Soares AM, Mota RM, Monteiro HS, Guerrant RL, Lima AA. Wasting and intestinal barrier function in children taking alanyl-glutamine-supplemented enteral formula. J Pediatr Gastroenterol Nutr. 2007 Mar;44(3):365-74. doi: 10.1097/MPG.0b013e31802eecdd.

    PMID: 17325559BACKGROUND
  • Moore SR, Quinn LA, Maier EA, Guedes MM, Quetz JS, Perry M, Ramprasad C, Lanzarini Lopes GML, Mayneris-Perxachs J, Swann J, Soares AM, Filho JQ, Junior FS, Havt A, Lima NL, Guerrant RL, Lima AAM. Intervention and Mechanisms of Alanyl-glutamine for Inflammation, Nutrition, and Enteropathy: A Randomized Controlled Trial. J Pediatr Gastroenterol Nutr. 2020 Sep;71(3):393-400. doi: 10.1097/MPG.0000000000002834.

MeSH Terms

Conditions

MalnutritionDiarrheaSprue, Tropical

Interventions

alanylglutamine

Condition Hierarchy (Ancestors)

Nutrition DisordersNutritional and Metabolic DiseasesSigns and Symptoms, DigestiveSigns and SymptomsPathological Conditions, Signs and SymptomsMalabsorption SyndromesIntestinal DiseasesGastrointestinal DiseasesDigestive System DiseasesMetabolic Diseases

Study Officials

  • Sean R Moore, MD, MS

    Cincinnati Children´s Hospital

    PRINCIPAL INVESTIGATOR
  • Aldo Lima, MD, PhD

    Universidade Federal do Ceara

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 12, 2013

First Posted

April 16, 2013

Study Start

October 1, 2013

Primary Completion

December 1, 2015

Study Completion

December 1, 2015

Last Updated

August 1, 2016

Record last verified: 2016-07

Locations