Long-term Impact and Intervention for Diarrhea in Brazil

• ClinicalTrials.gov Identifier: NCT00133406
• Recruitment Status: Unknown
• First Posted: August 23, 2005
• Last Update Posted: March 8, 2011
• Sponsor: University of Virginia
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID)
• Information provided by: University of Virginia

Study Description

Brief Summary:

The primary objectives of this study are to determine the effect of 1 year supplementation of Vitamin A, Zinc, and Vitamin A plus Zinc compared to placebo on the Height for Age Z Score (HAZ) and the number of episodes of diarrhea and number of days of diarrhea at one year in children living in a Brazilian slum. Study participants will include 280 children ages 2 months to 8 years old, with a Height for Age Z score (HAZ) less than median for the Parque Universitario community, living in Brazilian favela. There is also a sub study to determine if ten days of glutamine delivered as an oral bolus improves the health of the digestive system.

Condition or disease	Intervention/treatment	Phase
Diarrheal Disorder	Drug: Glutamine; Drug: Vitamin A; Drug: glycine; Drug: zinc	Phase 3

Detailed Description:

Study participants will include 280 children ages 2 months to 8 years old, with a Height for Age Z score (HAZ) less than median for the Parque Universitario community, living in Brazilian favela. Subjects will be enrolled into this prospective, randomized, placebo controlled study of the Long-term Impact and Intervention for Diarrhea in Brazil. Children meeting the inclusion criteria will be prospectively, randomized to four arms: (1) placebo: placebo (2) Vitamin A: Zinc Placebo (3) Vitamin A Placebo:Zinc (4) Vitamin A:Zinc. Intervention will last for one year with two additional years of follow up. A nested study involving all patients will take place at week four. At week four there will be a second randomization to either oral glutamine or glycine (placebo) for an additional ten days. The primary endpoint of the nested study will be the L:M ratio at 6 weeks. The master randomization list will be broken, only by combined approval of the Principal Investigators, at the end of the study or in the unexpected event of a child needing removal from the study (for that case only). All randomized subjects will be visited in their home two times per week for assessment of intercurrent diarrhea. At 1, 4, 8, 12, 24 and 36 months patients will have a nutritional status/anthropometry and diarrheal illness rate assessment. At 0, 1, 1.5, and 4 months all randomized subjects will have a Lactulose:Mannose Ratio (L:M) performed. A blood Zinc and Vitamin A level will be drawn at 0 and 4 months. Also a stool microbiology, lactoferrin and protein loss assessment will be completed at 1 month. All randomized subjects who complete the protocol should have assessments as outlined above at 36 weeks. The primary effect of interest is the difference in mean HAZ changes between children receiving Zinc plus Vitamin A compared to children receiving no Vitamin A or Zinc, averaging the difference in children receiving glutamine and children not receiving glutamine.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 321 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Long-term Impact and Intervention for Diarrhea in Brazil
• Study Start Date: June 2006
• Estimated Primary Completion Date: December 2011
• Estimated Study Completion Date: December 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: a; oral glutamine with juice for 10 days	Drug: Glutamine; 0.8gm/kg, ie up to a total daily dose of 16.2gm/day,with juice daily for 10 days
Experimental: b; PO vit A q 4 mo for 1 year plus zinc placebo	Drug: Vitamin A; 100,000 IU for children under 12 months of age (or placebo) and PO 200,000 IU for children at least 12 months of age (or placebo), both q months for 1 year at 0, 4 and 8 months.; Drug: zinc; 40 mg twice weekly for 12 months
Active Comparator: c; Zinc 40 mg twice weekly Plus Vitamin A Placebo for one year	Drug: Vitamin A; 100,000 IU for children under 12 months of age (or placebo) and PO 200,000 IU for children at least 12 months of age (or placebo), both q months for 1 year at 0, 4 and 8 months.; Drug: zinc; 40 mg twice weekly for 12 months
Placebo Comparator: d; oral glycine with juice daily for 10 days	Drug: glycine; 0.4gm/kg; ie up to 8.3gm/d, with juice daily for 10 days
Placebo Comparator: e; Vitamin A Placebo plus Zinc Placebo for one year	Drug: Vitamin A; 100,000 IU for children under 12 months of age (or placebo) and PO 200,000 IU for children at least 12 months of age (or placebo), both q months for 1 year at 0, 4 and 8 months.; Drug: zinc; 40 mg twice weekly for 12 months
Experimental: f; Vitamin A q 4 months and PO Zinc for 1 year	Drug: Vitamin A; 100,000 IU for children under 12 months of age (or placebo) and PO 200,000 IU for children at least 12 months of age (or placebo), both q months for 1 year at 0, 4 and 8 months.; Drug: zinc; 40 mg twice weekly for 12 months

Outcome Measures

Primary Outcome Measures :

1. L:M ratio at 1.5 months [ Time Frame: 1.5 months ]

Secondary Outcome Measures :

1. L:M ratio at 4 & 12 months [ Time Frame: 4 and 12 months ]
2. HAZ [ Time Frame: 1.5, 4, 8, 12, 24, and 36 months ]
3. Diarrhea burden [ Time Frame: 4, 8, 12, 24, and 36 months ]

Eligibility Criteria

• Ages Eligible for Study: 2 Months to 8 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Children ages 2 months to 8 years with height for age Z-score (HAZ) less than the median for the Parque Universitario community. Be a resident in Brazilian flavela. Child's parent or guardian must sign informed consent.

Exclusion Criteria:

Children exclusively breast-fed. Children who participated in the "hospital study" or any other study with in the past two years. Children with fever > 102 F at time of screening. Children with systemic disease at the time of screening including but not limited to: shock, meningitis, sepsis, pneumonia, tuberculosis, varicella. Children on antibiotics during screening. Children with siblings from the same household enrolled in this study.

Contacts and Locations

Contacts

Contact: Richard Guerrant; (434) 924-5242

Locations

Brazil

Federal University of Ceará; Recruiting

Fortaleza, Brazil, 60436160

Sponsors and Collaborators

University of Virginia

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Principal Investigator: Richard L Guerrant, MD; University of Virginia

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lima AA, Anstead GM, Zhang Q, Figueiredo IL, Soares AM, Mota RM, Lima NL, Guerrant RL, Oria RB. Effects of glutamine alone or in combination with zinc and vitamin A on growth, intestinal barrier function, stress and satiety-related hormones in Brazilian shantytown children. Clinics (Sao Paulo). 2014;69(4):225-33. doi: 10.6061/clinics/2014(04)02.

Lima AA, Kvalsund MP, Souza PP, Figueiredo IL, Soares AM, Mota RM, Lima NL, Pinkerton RC, Patrick PP, Guerrant RL, Oria RB. Zinc, vitamin A, and glutamine supplementation in Brazilian shantytown children at risk for diarrhea results in sex-specific improvements in verbal learning. Clinics (Sao Paulo). 2013;68(3):351-8. doi: 10.6061/clinics/2013(03)oa11.

Mitter SS, Oria RB, Kvalsund MP, Pamplona P, Joventino ES, Mota RM, Goncalves DC, Patrick PD, Guerrant RL, Lima AA. Apolipoprotein E4 influences growth and cognitive responses to micronutrient supplementation in shantytown children from northeast Brazil. Clinics (Sao Paulo). 2012;67(1):11-8. doi: 10.6061/clinics/2012(01)03.

Lima AA, Soares AM, Lima NL, Mota RM, Maciel BL, Kvalsund MP, Barrett LJ, Fitzgerald RP, Blaner WS, Guerrant RL. Effects of vitamin A supplementation on intestinal barrier function, growth, total parasitic, and specific Giardia spp infections in Brazilian children: a prospective randomized, double-blind, placebo-controlled trial. J Pediatr Gastroenterol Nutr. 2010 Mar;50(3):309-15. doi: 10.1097/MPG.0b013e3181a96489.

• Responsible Party: Richard Guerrant, University of VA
• ClinicalTrials.gov Identifier: NCT00133406
• Obsolete Identifiers: NCT00421382
• Other Study ID Numbers: 12475; 05-0071 ( Other Identifier: NIAID )
• First Posted: August 23, 2005
• Last Update Posted: March 8, 2011
• Last Verified: March 2011

Keywords provided by University of Virginia:

Brazil, Child Nutrition Disorders, Deficiency Diseases

Additional relevant MeSH terms:

Diarrhea; Signs and Symptoms, Digestive; Vitamin A; Glycine; Vitamins; Micronutrients; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Glycine Agents; Neurotransmitter Agents