Oral Cleft Prevention Trial in Brazil

Study Description

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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

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Study Type :	Interventional (Clinical Trial)
Estimated 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 :	January 2004
Actual Study Completion Date :	April 2007

Arms and Interventions

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Outcome Measures

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Primary Outcome Measures :

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

Secondary Outcome Measures :

1. Recurrence of NSCL/P compared to a historical control group; Overall and high versus low dose
2. Serum and red cell folate levels
3. Severity of NSCL/P in offspring of trial mothers
4. Twinning rate
5. Miscarriage rate
6. Preeclampsia
7. Rates of other birth defects
8. Birth weight
9. Gestational age

Eligibility Criteria

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Ages Eligible for Study:	16 Years to 45 Years (Child, Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

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.

Contacts and Locations

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Locations

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, Brazil

Sponsors and Collaborators

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

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

Bill and Melinda Gates Foundation

National Institute of Dental and Craniofacial Research (NIDCR)

John E. Fogarty International Center (FIC)

National Center for Complementary and Integrative Health (NCCIH)

National Cancer Institute (NCI)

RTI International

University of Iowa

Hospital de Reabilitação de Anomalias Craniofaciais (HRAC) - Brazil

Investigators

Principal Investigator:	Jeff Murray, M.D.	University of Iowa

More Information

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Additional Information:

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

RTI International 

Responsible Party:	NICHD Global Network for Women's and Children's Health
ClinicalTrials.gov Identifier:	NCT00098319 History of Changes
Other Study ID Numbers:	GN 04 Aim III
First Posted:	December 7, 2004
Last Update Posted:	December 17, 2013
Last Verified:	December 2013

Keywords provided by NICHD Global Network for Women's and Children's Health:

Maternal and child health; Women's health; Cleft palate; Cleft lip; Folic acid; Global Network; International	Brazil; Brasil; Latin America; ECLAMC; Congenital defects; Pregnancy

Additional relevant MeSH terms:

Cleft Lip; Cleft Palate; Lip Diseases; Mouth Diseases; Stomatognathic Diseases; Mouth Abnormalities; Stomatognathic System Abnormalities; Congenital Abnormalities; Jaw Abnormalities; Jaw Diseases; Musculoskeletal Diseases	Maxillofacial Abnormalities; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Folic Acid; Vitamin B Complex; Hematinics; Vitamins; Micronutrients; Growth Substances; Physiological Effects of Drugs