Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy

Malnutrition Clinical Trial

— IMAGINE  

Official title:

Intervention and Mechanisms of Alanyl-Glutamine for Inflammation, Nutrition, and Enteropathy (IMAGINE)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01832636
• Other study ID #: CIN001 -"IMAGINE"
• Status: Completed
• Phase: Phase 3
• First received: April 12, 2013
• Last updated: July 28, 2016
• Start date: October 2013
• Est. completion date: December 2015

Study information

• Verified date: July 2016
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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?

Recruitment information / eligibility

• Status: Completed
• Enrollment: 112
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Months to 5 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diarrhea
• Environmental Enteropathy
• Inflammation
• Intestinal Diseases
• Malnutrition

Intervention

Dietary Supplement:
• Alanyl-Glutamine
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.

Locations

Country	Name	City	State
Brazil	Universidade Federal do Ceara	Fortaleza	Ceara

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Universidade Federal do Ceara

Country where clinical trial is conducted

Brazil, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Fecal Lactoferrin Test	To evaluate the effect of time and dose-response of alanyl-glutamine on intestinal inflammation, as measured by qualitative or quantitative testing for fecal lactoferrin in stools of children at risk of undernutrition.	Fecal sample collected on Day 1, 10-13, 30-37	No
Secondary	Fecal Cytokine Measurement	To evaluate the effect of alanyl-glutamine on intestinal inflammation, by measuring proinflammatory cytokines interleukin-1, interleukin-8, tumor necrosis factor-alpha (TNF), and regenerating gene 1B (REG1B) in stools of children at risk of undernutrition.	Fecal sample collected on Day 1, 10-13	No
Secondary	Anthropometry	To evaluate the time and dose-effect of alanyl-glutamine on short and medium-term nutritional status by evaluating changes in anthropometric measures (z scores) over time: height-for-age, weight-for-age, and weight-for-height.	Measured and calculated Day 1, 10-13, 30-37, 90-104, 120-141	No
Secondary	Fecal Calorimetry	To evaluate the effect of time and dose-response of alanyl-glutamine on the intestinal absorption of fat, protein, and carbohydrates, by measurement of fecal energy content by bomb calorimetry.	Fecal sample collected on Day 1, 10-13, 30-37	No
Secondary	Metabolomic Profile of Urine	To evaluate the time and dose-effect of alanyl-glutamine on metabolism in children at risk of undernutrition by means of urine metabolomic profile tests.	Collected on Day 1, 10-13, 30-37	No
Secondary	History of Diarrhea in the Previous Two Weeks	History of diarrhea in the previous two weeks. A day of diarrhea will be defined as 3 or more looser than normal bowel movements in a 24-hour period. Distinct episodes must be separated by at least 2 days without diarrhea. Duration of episodes will be classified as acute (< 7 days), prolonged acute (>6 and <14 days), or persistent (>13 days).	Day 1, 30-37, 90-104, 120-141	No