Cleft LipPhase 3NCT00397917
Oral Cleft Prevention Program
A Phase 3 study testing Folic acid: 4 mg versus 0.4 mg per day in people with Cleft Lip and Cleft Palate, run by University of Iowa at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 45 years, women only
- Conditions the study is for
- Cleft Lip, Cleft Palate
- What is being tested?
- Folic acid: 4 mg versus 0.4 mg per day
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4,000 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2006to Jul 2013
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 45 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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
- Being tested
- Folic acid: 4 mg versus 0.4 mg per day
- Medical subject headings
- Cleft Lip, Cleft Palate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Folic acid: 4 mg versus 0.4 mg per dayDrug
Folic acid
| Study group | Role | What they receive |
|---|---|---|
| 400 micrograms of folic acid | Active comparator | Blinded study with two arms one of 400ug in arm 1 Receives: Drug: Folic acid: 4 mg versus 0.4 mg per day |
| 4mg of folic acid | Active comparator | Second arm is 4mg of folic acid in arm 2 Receives: Drug: Folic acid: 4 mg versus 0.4 mg per day |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence of cleft lip and palate
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2006 (estimated)
- Study startNov 2006
- Primary completionMay 2012
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cleft LipStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4,000 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Collaborators
- 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
- Responsible party
- Principal investigator, Jeff Murray, University of Iowa
- Investigators
- Jeffrey Murray, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00397917
- Sponsor's protocol ID
- NIDCR-17958
- Other IDs
- U01DE017958
- Status last verified
- Mar 2017
- First submitted
- 8 Nov 2006
- Last updated
- 31 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual level data will not be shared unless de-identified
Publications
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.
PubMed 23669628Wehby 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.
PubMed 23181832
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Oral Cleft Prevention Program
- ClinicalTrials.gov ID
- NCT00397917
- Acronym / sponsor ID
- NIDCR-17958
- Conditions
- Cleft Lip, Cleft Palate
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,000 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Collaborators
- 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
- Study start
- Nov 2006
- Primary completion
- May 2012 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 10 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 400 micrograms of folic acid | Active comparator | Drug: Folic acid: 4 mg versus 0.4 mg per dayBlinded study with two arms one of 400ug in arm 1 |
| 4mg of folic acid | Active comparator | Drug: Folic acid: 4 mg versus 0.4 mg per daySecond arm is 4mg of folic acid in arm 2 |
Who may qualify
- Ages
- 16 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (7 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Folic acid: 4 mg versus 0.4 mg per dayFolic acid | Drug | 400 micrograms of folic acid, 4mg of folic acid |
Primary outcome
Recurrence of cleft lip and palate
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2017.
- Results publication: PubMed 23669628Vila-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.
- Derived from this study: PubMed 23181832Wehby 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.
- Individual participant dataSharing planned: No. Individual level data will not be shared unless de-identified
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jeffrey Murray, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Folic acid: 4 mg versus 0.4 mg per day in people with Cleft Lip and Cleft Palate, run by University of Iowa at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recurrence of cleft lip and palate (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00397917, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Mar 2017.