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

NCT ID: NCT01832636

Last Updated: 2016-08-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 112 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-10-31
• Study Completion Date: 2015-12-31

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?

Conditions

Malnutrition; Environmental Enteropathy; Diarrhea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Alanyl-Glutamine 3g/d

Alanyl-Glutamine orally 3g/day for 10 days

Group Type: ACTIVE_COMPARATOR

Alanyl-Glutamine

Intervention Type: DIETARY_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.

Alanyl-Glutamine 6g/d

Alanyl-Glutamine orally 6g/day for 10 days

Group Type: ACTIVE_COMPARATOR

Alanyl-Glutamine

Intervention Type: DIETARY_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.

Alanyl-Glutamine 12g/d

Alanyl-Glutamine orally 12g/d for 10 days

Group Type: ACTIVE_COMPARATOR

Alanyl-Glutamine

Intervention Type: DIETARY_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.

Glycine 12.5g/d

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

Group Type: PLACEBO_COMPARATOR

Alanyl-Glutamine

Intervention Type: DIETARY_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.

Interventions

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.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

AminoStable (Ajinomoto)

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.

• Minimum Eligible Age: 2 Months
• Maximum Eligible Age: 5 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universidade Federal do Ceara

OTHER

Sponsor Role: collaborator

Children's Hospital Medical Center, Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sean R Moore, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Cincinnati Children´s Hospital

Aldo Lima, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universidade Federal do Ceara

Locations

Universidade Federal do Ceara

Fortaleza, Ceará, Brazil

Countries

Brazil

References

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.

Reference Type: BACKGROUND

PMID: 17325559 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32826717 (View on PubMed)

Other Identifiers

CIN001 -"IMAGINE"

Identifier Type: -

Identifier Source: org_study_id