Oral Cleft Prevention Trial in Brazil

This study has been completed.
Sponsor:
Collaborators:
Global Network for Women's and Children's Health Research
Bill and Melinda Gates Foundation
RTI International
University of Iowa
Hospital de Reabilitação de Anomalias Craniofaciais (HRAC) - Brazil
Information provided by (Responsible Party):
NICHD Global Network for Women's and Children's Health
ClinicalTrials.gov Identifier:
NCT00098319
First received: December 6, 2004
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Cleft Lip
Cleft Palate
Drug: Folic acid (0.4mg vs. 4.0mg)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Oral Cleft Prevention Trial in Brazil

Resource links provided by NLM:


Further study details as provided by NICHD Global Network for Women's and Children's Health:

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

Estimated Enrollment: 2200
Study Start Date: January 2004
Study Completion Date: April 2007
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

Ages Eligible for Study:   16 Years to 45 Years
Genders 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00098319

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
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

Additional Information:
No publications provided

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
Study First Received: December 6, 2004
Last Updated: December 16, 2013
Health Authority: United States: Federal Government

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 Palate
Cleft Lip
Jaw Abnormalities
Jaw Diseases
Musculoskeletal Diseases
Maxillofacial Abnormalities
Craniofacial Abnormalities
Musculoskeletal Abnormalities
Stomatognathic Diseases
Mouth Abnormalities
Mouth Diseases
Stomatognathic System Abnormalities
Congenital Abnormalities
Lip Diseases
Folic Acid
Vitamin B Complex
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 16, 2014