Long-term Impact and Intervention for Diarrhea in Brazil

University of Virginia

Status and phase: Unknown; Phase 3

Conditions: Diarrheal Disorder

Treatments: Drug: Glutamine; Drug: zinc; Drug: glycine; Drug: Vitamin A

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00133406

05-0071 (Other Identifier)

12475

Details and patient eligibility

About

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.

Full 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.

Enrollment: 321 estimated patients

Sex: All

Ages: 2 months to 8 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Quadruple Blind

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321 participants in 6 patient groups, including a placebo group

a

Experimental group

Description:

oral glutamine with juice for 10 days

Treatment:

Drug: Glutamine

b

Experimental group

Description:

PO vit A q 4 mo for 1 year plus zinc placebo

Treatment:

Drug: Vitamin A

Drug: zinc

c

Active Comparator group

Description:

Zinc 40 mg twice weekly Plus Vitamin A Placebo for one year

Treatment:

Drug: Vitamin A

Drug: zinc

d

Placebo Comparator group

Description:

oral glycine with juice daily for 10 days

Treatment:

Drug: glycine

e

Placebo Comparator group

Description:

Vitamin A Placebo plus Zinc Placebo for one year

Treatment:

Drug: Vitamin A

Drug: zinc

f

Experimental group

Description:

Vitamin A q 4 months and PO Zinc for 1 year

Treatment:

Drug: Vitamin A

Drug: zinc