Clinical trial NCT01832636: Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy
Official title: Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy (IMAGINE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malnutrition
Environmental Enteropathy
Diarrhea
Keywords: L-Alanyl-L-Glutamine
Environmental enteric dysfunction
Tropical enteropathy
Lead sponsor: Children's Hospital Medical Center, Cincinnati
Sponsor class: OTHER
Collaborators: name: Universidade Federal do Ceara
First posted: 2013-04-16
Enrollment: 112
Sex: ALL
Minimum age (years): 2
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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?


Eligibility criteria: Inclusion Criteria:

1. 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.
2. Children ages 2 months to 5 years old.

Exclusion Criteria:

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

Primary outcomes:
measure: Urinary Lactulose: Mannitol Intestinal Permeability Test
timeFrame: Urine Collection on Day 1, 10-13, 30-37
Secondary outcomes:
measure: Fecal Lactoferrin Test
timeFrame: Fecal sample collected on Day 1, 10-13, 30-37
measure: Fecal Cytokine Measurement
timeFrame: Fecal sample collected on Day 1, 10-13
measure: Anthropometry
timeFrame: Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141
measure: Fecal Calorimetry
timeFrame: Fecal sample collected on Day 1, 10-13, 30-37
measure: Metabolomic Profile of Urine
timeFrame: Collected on Day 1, 10-13, 30-37
measure: History of Diarrhea in the Previous Two Weeks
timeFrame: Day 1, 30-37, 90-104, 120-141
Other outcomes:
Locations:
city: Fortaleza
country: Brazil
facility: Universidade Federal do Ceara
state: Ceara
Study officials:
affiliation: Cincinnati Children´s Hospital
name: Sean R Moore, MD, MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Universidade Federal do Ceara
name: Aldo Lima, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.