Oral Cleft Prevention Program

NCT ID: NCT00397917

Last Updated: 2017-03-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 4000 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2013-07-31

Brief Summary

The purpose of this study is to asses if taking 4 mg of folic acid per day at preconception and during the first three months of pregnancy decreases the risk of having a child with cleft lip and palate compared to 0.4 mg folic acid for women who have an oral cleft or have had previously child with an oral cleft.

Detailed Description

Cleft lip and palate is a common and burdensome birth defect that has large health ramifications and requires surgical, speech, behavioral, dental, and medical interventions. There is some evidence suggesting that taking folic acid particularly at large doses during preconception and first trimester of pregnancy may decrease the risk of oral cleft recurrence, which is the risk of having a child with an oral cleft for women who have an oral cleft or who have had a child with a cleft. However this evidence is based on study designs that are incapable of contributing the preventive effects to folic acid with adequate confidence, and the real effect of folic acid on cleft recurrence prevention remains to be identified. Taking 4 mg of folic acid per day at preconception and first trimester of pregnancy has also been shown to prevent the recurrence of neural tube defects by up to 70%, providing further support to evaluate this intervention for oral cleft recurrence.

This study evaluates the effects of supplementation with 4 versus 0.4 mg of folic acid per day at preconception and during the first three months of pregnancy on recurrence of cleft lip and palate. Up to 6000 women will be randomly assigned to 4 versus 0.4 mg groups. The primary aim is to compare the recurrence rates in the offspring of trial mothers in the two groups. Secondary aims are to compare the two groups on several outcomes including miscarriage, twinning, pre-eclampsia, serum and red cell folate levels, severity of oral clefts and occurrence of other birth defects in the offspring of trial mothers, and birth weight and gestational age of trial babies, and to compare the recurrence in the two groups to that in historic controls.

Conditions

Cleft Lip; Cleft Palate

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

400 micrograms of folic acid

Blinded study with two arms one of 400ug in arm 1

Group Type: ACTIVE_COMPARATOR

Folic acid: 4 mg versus 0.4 mg per day

Intervention Type: DRUG

Folic acid

4mg of folic acid

Second arm is 4mg of folic acid in arm 2

Group Type: ACTIVE_COMPARATOR

Folic acid: 4 mg versus 0.4 mg per day

Intervention Type: DRUG

Folic acid

Interventions

Folic acid: 4 mg versus 0.4 mg per day

Folic acid

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Women with cleft lip with/out palate (CLP), 16 to 45 years of age registered at the study clinics in Brazil or Women (16 to 45 years of age) with at least one natural child of any age with CLP registered at the study clinics.
• Women must reside in the catchment area of the study, which includes the states where the study clinics are located and surrounding states.

Exclusion Criteria

• Consanguineous couples (up to third degree, i.e. first cousins or closer).
• Pregnany at the time of recruitment. Women will be recontacted later at an appropriate time for participation in the study.
• Couples either one of which have been sterilized.
• Taking any form of seizure medication.
• Planning to move outside of the study catchment area within the next year.
• B12 deficiency (<174 pg/mL or 129.15 pmol/L).
• Being allergic to folic acid.

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Dental and Craniofacial Research (NIDCR)

NIH

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

RTI International

OTHER

Sponsor Role: collaborator

University of Sao Paulo

OTHER

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: lead

Responsible Party

Jeff Murray

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey Murray, MD

Role: PRINCIPAL_INVESTIGATOR

University of Iowa

Locations

University of Iowa

Iowa City, Iowa, United States

Countries

United States

References

Vila-Nova C, Wehby GL, Queiros FC, Chakraborty H, Felix TM, Goco N, Moore J, Gewehr EV, Lins L, Affonso CM, Murray JC. Periconceptional use of folic acid and risk of miscarriage - findings of the Oral Cleft Prevention Program in Brazil. J Perinat Med. 2013 Jul;41(4):461-6. doi: 10.1515/jpm-2012-0173.

Reference Type: RESULT

PMID: 23669628 (View on PubMed)

Wehby GL, Goco N, Moretti-Ferreira D, Felix T, Richieri-Costa A, Padovani C, Queiros F, Guimaraes CV, Pereira R, Litavecz S, Hartwell T, Chakraborty H, Javois L, Murray JC. Oral cleft prevention program (OCPP). BMC Pediatr. 2012 Nov 26;12:184. doi: 10.1186/1471-2431-12-184.

Reference Type: DERIVED

PMID: 23181832 (View on PubMed)

Other Identifiers

U01DE017958

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIDCR-17958

Identifier Type: -

Identifier Source: org_study_id