Oral Cleft Prevention Trial in Brazil

Sponsor

NICHD Global Network for Women's and Children's Health (Other)

Overall Status

Completed

CT.gov ID

NCT00098319

Collaborator

Global Network for Women's and Children's Health Research (Other), Bill and Melinda Gates Foundation (Other), National Institute of Dental and Craniofacial Research (NIDCR) (NIH), Fogarty International Center of the National Institute of Health (NIH), National Center for Complementary and Integrative Health (NCCIH) (NIH), National Cancer Institute (NCI) (NIH), RTI International (Other), University of Iowa (Other), Hospital de Reabilitação de Anomalias Craniofaciais (HRAC) - Brazil (Other)

2,200

Enrollment

Locations

Duration (Months)

733.3

Patients Per Site

18.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Cleft lip and palate are a significant component of morbid human birth defects in the developing world. By supplementing a high-risk group of women with folic acid (4.0 mg versus 0.4 mg) from preconception and continuing throughout the first 3 months of pregnancy in the state of Sao Paulo, Brazil, this study aims to reduce the recurrence of cleft lip and palate.

Condition or Disease	Intervention/Treatment	Phase
Cleft Lip Cleft Palate	Drug: Folic acid (0.4mg vs. 4.0mg)	Phase 3

Detailed Description

Craniofacial anomalies and cleft lip with or without cleft palate (CL/P) are a model for the impact of birth defects on fetal and neonatal health directly and maternal health indirectly. Craniofacial anomalies comprise a significant component of morbid human birth defects. The primary hypothesis is that folic acid supplementation of 4mg/day at preconception and during the first three months of pregnancy will decrease the recurrence of nonsyndromic cleft lip with or without clef palate (NSCL/P) in a high-risk group of women when compared to women taking 0.4 mg per day of folic acid. The total sample will include 2,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg versus the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects as well as the two study groups (4mg, 0.4 mg) to that of a historical control group.

The primary outcome assessed is the rate of recurrences of NSCL/P in offspring of the trial mothers in each of the two study groups. Secondary outcomes include recurrence of NSCL/P compared to a historical control group; serum and red cell folate levels; severity of NSCL/P in offspring of trial mothers; twinning rate; miscarriage rate; preeclampsia; rates of other birth defects; birth weight; and gestational age. The sample size was based on historic tables of birth rates and the rates of cleft occurrences. The study hypothesizes that a total of 2000 subjects will be enrolled during a 2.5 year period; a dropout rate of 10%; birth rate for group A (women with NSCL/P) of 10% and a rate of 12% for group B (women with at least one child with NSCL/P); risk of cleft for group A is 7% and for group B is 4%; one-sided test with continuity correction.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

2200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double

Primary Purpose:

Prevention

Official Title:

Oral Cleft Prevention Trial in Brazil

Study Start Date :

Jan 1, 2004

Actual Study Completion Date :

Apr 1, 2007

Outcome Measures

Primary Outcome Measures

Recurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring of trial mothers []

Secondary Outcome Measures

Recurrence of NSCL/P compared to a historical control group; Overall and high versus low dose []
Serum and red cell folate levels []
Severity of NSCL/P in offspring of trial mothers []
Twinning rate []
Miscarriage rate []
Preeclampsia []
Rates of other birth defects []
Birth weight []
Gestational age []

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

All women must reside in the state where the clinic is located.
Women with NSCL/P who attend the craniofacial clinics, who are 16 to 45 years of age (after age 45 fecundity decreases substantially)who attend the craniofacial clinic for their care.
Women (ages 16 to 45 years of age) who have at least one natural child of any age with NSCL/P who receives care at the participating craniofacial clinics.

Exclusion Criteria:

Cases resulting from consanguineous couples (first, second, and third degree, i.e., first cousins or closer).
Couples where at least one of the two is definitely sterilized.
Women on anti-epileptic drugs.
Women who are pregnant.
Women who are planning to move outside of the state where the clinic is located within the next year.
Women who are planning to move outside of Sao Paulo state within the next year.
Women who have B12 deficiency (B12 level is below 174 pg/ml or 134.328 pmol/L).
Women who have an allergy to folic acid.

Contacts and Locations

Locations

	Site	City	State	Country
1	Hospital de Reabilitação de Anomalias Craniofaciais (HRAC)	Bauru	Sao Paulo	Brazil
2	Hospital de Clinicas de Porto Alegre (HCPA)	Porto Alegre		Brazil
3	Hospital Santo Antonio-Centrinho: Obras Sociais Irma Dulce	Salvador		Brazil