Oral Cleft Prevention Program

Sponsor

University of Iowa (Other)

Overall Status

Completed

CT.gov ID

NCT00397917

Collaborator

National Institute of Dental and Craniofacial Research (NIDCR) (NIH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH), RTI International (Other), University of Sao Paulo (Other)

4,000

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cleft Lip Cleft Palate	Drug: Folic acid: 4 mg versus 0.4 mg per day	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

4000 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Random number assignments

Primary Purpose:

Prevention

Official Title:

Oral Cleft Prevention Program

Study Start Date :

Nov 1, 2006

Actual Primary Completion Date :

May 1, 2012

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 400 micrograms of folic acid Blinded study with two arms one of 400ug in arm 1	Drug: Folic acid: 4 mg versus 0.4 mg per day Folic acid
Active Comparator: 4mg of folic acid Second arm is 4mg of folic acid in arm 2	Drug: Folic acid: 4 mg versus 0.4 mg per day Folic acid

Arm

Intervention/Treatment

Active Comparator: 400 micrograms of folic acid

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

Drug: Folic acid: 4 mg versus 0.4 mg per day

Folic acid

Active Comparator: 4mg of folic acid

Second arm is 4mg of folic acid in arm 2

Drug: Folic acid: 4 mg versus 0.4 mg per day

Folic acid

Outcome Measures

Primary Outcome Measures

Recurrence of cleft lip and palate [3 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 45 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Iowa	Iowa City	Iowa	United States	52242

Sponsors and Collaborators

University of Iowa
National Institute of Dental and Craniofacial Research (NIDCR)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
RTI International
University of Sao Paulo

Investigators

Principal Investigator: Jeffrey Murray, MD, University of Iowa

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jeff Murray, Professor of Pediatrics, University of Iowa

ClinicalTrials.gov Identifier:

NCT00397917

Other Study ID Numbers:

NIDCR-17958
U01DE017958

First Posted:

Nov 10, 2006

Last Update Posted:

Mar 31, 2017

Last Verified:

Mar 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Cleft Palate

Cleft Lip

Folic Acid

Study Results

No Results Posted as of Mar 31, 2017