Clinical trial NCT00098319: Oral Cleft Prevention Trial in Brazil
Official title: Oral Cleft Prevention Trial in Brazil
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cleft Lip
Cleft Palate
Keywords: Cleft palate
Cleft lip
Folic acid
Global Network
Maternal and child health
International
Women's health
Brazil
Brasil
Latin America
ECLAMC
Congenital defects
Pregnancy
Lead sponsor: NICHD Global Network for Women's and Children's Health
Sponsor class: NETWORK
Collaborators: name: Global Network for Women's and Children's Health Research
name: Bill and Melinda Gates Foundation
name: National Institute of Dental and Craniofacial Research (NIDCR)
name: Fogarty International Center of the National Institute of Health
name: National Center for Complementary and Integrative Health (NCCIH)
name: National Cancer Institute (NCI)
name: RTI International
name: University of Iowa
name: Hospital de Reabilitação de Anomalias Craniofaciais (HRAC) - Brazil
First posted: 2004-12-07
Enrollment: 2200
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Recurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring of trial mothers
Secondary outcomes:
measure: Recurrence of NSCL/P compared to a historical control group; Overall and high versus low dose
measure: Serum and red cell folate levels
measure: Severity of NSCL/P in offspring of trial mothers
measure: Twinning rate
measure: Miscarriage rate
measure: Preeclampsia
measure: Rates of other birth defects
measure: Birth weight
measure: Gestational age
Other outcomes:
Locations:
city: Bauru
country: Brazil
facility: Hospital de Reabilitação de Anomalias Craniofaciais (HRAC)
state: Sao Paulo
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre (HCPA)
city: Salvador
country: Brazil
facility: Hospital Santo Antonio-Centrinho: Obras Sociais Irma Dulce
Study officials:
affiliation: University of Iowa
name: Jeff Murray, M.D.
role: PRINCIPAL_INVESTIGATOR
References: