Oral Cleft Prevention Trial in Brazil

Cleft Palate Clinical Trial

Official title:

Oral Cleft Prevention Trial in Brazil

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00098319
• Other study ID #: GN 04 Aim III
• Status: Completed
• Phase: Phase 3
• First received: December 6, 2004
• Last updated: December 16, 2013
• Start date: January 2004
• Est. completion date: April 2007

Study information

• Verified date: December 2013
• Source: NICHD Global Network for Women's and Children's Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2200
• Est. completion date: April 2007
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 45 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cleft Lip
• Cleft Palate

Intervention

Drug:
• Folic acid (0.4mg vs. 4.0mg)

Locations

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

Sponsors (10)

Lead Sponsor

Collaborator

NICHD Global Network for Women's and Children's Health

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

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Recurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring of trial mothers
Secondary	Recurrence of NSCL/P compared to a historical control group; Overall and high versus low dose
Secondary	Serum and red cell folate levels
Secondary	Severity of NSCL/P in offspring of trial mothers
Secondary	Twinning rate
Secondary	Miscarriage rate
Secondary	Preeclampsia
Secondary	Rates of other birth defects
Secondary	Birth weight
Secondary	Gestational age

External Links

•   Global Network for Women's and Children's Health Research
•   RTI International