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Congenital MalformationsPhase 3NCT01244347

Folic Acid Dosage and Malformations Reduction

A Phase 3 study testing folic acid in people with Congenital Malformations, run by Azienda Ospedaliera Universitaria Integrata Verona at 34 sites in Italy.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

In 1991 the Medical Research Council Vitamin Study Group and in 1992 the Hungarian randomised clinical trial have shown conclusively that the risk of neural tube defects can be reduced substantially by taking folic acid during the peri-conceptional period. Read more about this study

Who is it for?
Ages 18 to 44 years, women only
Conditions the study is for
Congenital Malformations
What is being tested?
folic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
5,000 participants
Where
34 sitesItaly
Study dates
Jul 2009to Sep 2016
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 18 to 44 years
  • Women only
  • No healthy volunteers
  • Adult

Who may be able to join

  • age between 18 and 44 years
  • women who intend to become pregnant (not excluded women

Who cannot join

  • pregnant women
  • women planning to move to an area where the study is not ongoing
  • women who do not understand and speak Italian
  • women who do not have a phone
  • women affected by epilepsy, even not assuming anticonvulsivant drugs
  • women affected by diabetes
Show all 19Show fewer
  • women who previously had a tumour or a disease relevant for the study (Crohn disease, rheumatoid arthritis, ulcerative colitis)
  • women who recently assumed antifolates, like methotrexate
  • women who currently abuse or previously abused alcohol
  • obese women
  • vegetarian women
  • women who had a previous pregnancy with neural tube defect (NTD) or any other congenital structural defect
  • women or partners with NTD, or one of their relatives with an NTD
  • women with positive family history for breast or colorectal cancer
  • women with positive family or personal history of hereditary syndrome like adenomatous polyposis, or hereditary nonpolyposis colorectal cancer
  • women allergic to folic acid
  • women presenting contraindications to folic acid
  • women affected by megaloblastic anaemia
  • assuming folic acid at defined doses for conditions other than those already mentioned

Trial locations and contacts

34 sites in 1 country.

34 sites in 1 country

Italy34 sites

  • Ospedale di Adria

    Adria, Rovigo, 45011

  • Family Health Centre

    Bassano, Vicenza, 36061

  • Ospedale San Bassiano

    Bassano, Vicenza, 36061

  • Ospedale di Bussolengo

    Bussolengo, Verona, 37012

  • Family Health Practice

    Camponogara, Venezia, 30010

  • Ospedale di Conegliano

    Conegliano, Treviso, 31015

  • General Practice

    Dueville, Vicenza, 36031

  • Ospedale Sant'Antonio Abate

    Gallarate, Varese, 21013

  • Ospedale di Legnago

    Legnago, Verona, 37045

  • General Practice

    Malo, Vicenza, 36034

  • Family Health Centre

    Martellago, Venezia, 30030

  • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico

    Milan, 20100

  • Family Health Practice

    Mira, Venezia, 30034

  • Family Health Centre

    Montebelluna, Treviso, 31044

  • Family Health Centre

    Noale, Venezia, 30033

  • Family Health Practice

    Oderzo, Treviso, 31046

  • Azienda Ospedaliera di Padova

    Padova, 35100

  • Family Health Centre

    Padova, 35132

  • Ospedale di San Bonifacio

    San Bonifacio, Verona, 37047

  • Family Health Centre

    San Pietro di Stra, Venezia, 30031

  • General Practice

    Schio, Vicenza, 36014

  • General Practice

    Sovizzo, Vicenza, 36050

  • Ospedale Boldrini

    Thiene, Vicenza, 36016

  • Ospedale San Luca

    Trecenta, Rovigo, 45027

  • Ospedale di Valdagno

    Valdagno, Vicenza, 36078

  • Family Health Centre

    Verona, 37122

  • General Practice

    Verona, 37126

  • Ospedale Civile Maggiore

    Verona, 37126

  • General Practice

    Verona, 37129

  • Family Health Centre

    Verona, 37131

  • Policlinico G.B. Rossi

    Verona, 37134

  • Ospedale di Vicenza

    Vicenza, VI, 36100

  • Family Health Practice

    Villorba, Treviso, 31020

  • Family Health Centre

    Vogonovo, Venezia, 30030

Other trials in Italy

About this study

Official title: Randomized Clinical Trial to Evaluate the Efficacy of High Dose of Folic Acid to Prevent the Occurrence of Congenital Malformations

In 1991 the Medical Research Council Vitamin Study Group and in 1992 the Hungarian randomised clinical trial have shown conclusively that the risk of neural tube defects can be reduced substantially by taking folic acid during the peri-conceptional period. At present there is enough evidence to support the hypothesis that folic acid supplementation can reduce the risk of all congenital malformations or of a specific and selected group of them, namely: neural tube defects, oral clefts, cardiac defects, urinary tract anomalies except hypospadias, limb reduction defects, omphalocele, anal atresia and trisomy 21.

The hypothesis that a higher intake of folic acid is related to an higher risk reduction of neural tube defects and of other congenital malformations is the main rationale for the present study.

Read more

The present study is a randomized, double-blind, controlled trial evaluating whether supplementation with folic acid at high dose (4 mg/day) reduces the overall risk of major congenital malformations in the population more than the standard recommended dose (0.4 mg/day). At the enrolment visit all the eligible women will be interviewed to assess sociodemographic, life style and health status. After randomization, women will be interviewed every 4 months to evaluate pregnancy status. Women who have a pregnancy diagnosis during the study period will be interviewed by telephone at the expected 16, 24 and 40 weeks of gestation to evaluate the pregnancy outcome. The health status of live births will be evaluated at the child's age of 1 month, 3 months and 1 year.

The primary aim of this project is conducting a study to assess the effect of folic acid periconceptional supplementation of 4 mg/day compared to the 0.4 mg/day standard dose on reducing the occurrence of all congenital malformations. Secondary aims of this study include comparing severity of CMs in offspring of trial mothers, rates of "selected congenital malformations", rates of twinning, miscarriages, recurrent abortions, small-for-gestational age, preeclampsia and abruptio placentae. The sample size is not easy to be computed because lacking robust estimate of the size effect of the treatment. Three hypotheses of a size effect of 45%, 26% and 13% were considered. A sample size of outcomes (and women) respectively of 2,006 (5,015), 8,510 (21,275) and 30,126 (75,315) is needed. Since the sample size needed to evaluate different scenarios is large, the present study is also the pilot study to promote an international prospective meta-analysis.

Being tested
folic acid
Keywords
folic acid, malformations, prevention
Medical subject headings
Congenital Abnormalities

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • folic acidDrug

  • folic acidDrug

Study groups in NCT01244347
Study groupRoleWhat they receive
folic acid 4 mgExperimentalNot described
Receives: Drug: folic acid
folic acid 0.4 mgActive comparatorNot described
Receives: Drug: folic acid

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. number of congenital malformations

    The time frame was computed as an average of 32 weeks before conception, plus an average of 28 weeks to all possible outcomes, plus 52 weeks of baby observation.

    Measured: 112 weeks

Secondary outcomes (7)

  1. rate of selected congenital malformations

    The time frame was computed as an average of 32 weeks before conception, plus an average of 28 weeks to all possible outcomes, plus 52 weeks of baby observation.

    Measured: 112 weeks

  2. Miscarriages and recurrent abortions

    The time frame was computed as an average of 32 weeks before conception, plus an average of 15 weeks as a mean of time from conception to different clinical conditions related to miscarriage.

    Measured: 47 weeks

  3. pre-eclampsia

    The time frame was computed as an average of 32 weeks before conception, plus an average of 28 weeks to the occurrence of pre-eclampsia.

    Measured: 60 weeks

  4. abruptio placentae

    The time frame was computed as an average of 32 weeks before conception, plus an average of 34 weeks to the occurrence of abruptio placentae.

    Measured: 34 weeks

  5. intrauterine growth restriction

    The time frame was computed as an average of 32 weeks before conception, plus an average of 31 weeks to the occurrence of intrauterine growth restriction.

    Measured: 31 weeks

  6. pre-term delivery

    The time frame was computed as an average of 32 weeks before conception, plus an average of 30 weeks to the occurrence of pre-term delivery.

    Measured: 30 weeks

  7. multiple births

    The time frame was computed as an average of 32 weeks before conception, plus an average of 24 weeks to the possible diagnosis of twinnings or delivery.

    Measured: 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Nov 2010 (estimated)
  2. Study startJul 2009
  3. Primary completionSep 2015 (estimated)
  4. Study completionSep 2016 (estimated)

Resources

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
5,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01244347
Sponsor's protocol ID
FARM 6KWTCT
Other IDs
2008-004334-25, 2008
Status last verified
Jan 2015
First submitted
11 Oct 2010
Last updated
14 Jan 2015
Results posted
No
Data monitoring committee
Yes

Publications

  • Badovinac RL, Werler MM, Williams PL, Kelsey KT, Hayes C. Folic acid-containing supplement consumption during pregnancy and risk for oral clefts: a meta-analysis. Birth Defects Res A Clin Mol Teratol. 2007 Jan;79(1):8-15. doi: 10.1002/bdra.20315.

    PubMed 17133404

  • Berry RJ, Li Z, Erickson JD, Li S, Moore CA, Wang H, Mulinare J, Zhao P, Wong LY, Gindler J, Hong SX, Correa A. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med. 1999 Nov 11;341(20):1485-90. doi: 10.1056/NEJM199911113412001.

    PubMed 10559448

  • Botto LD, Olney RS, Erickson JD. Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet. 2004 Feb 15;125C(1):12-21. doi: 10.1002/ajmg.c.30004.

    PubMed 14755429

  • Catov JM, Bodnar LM, Ness RB, Markovic N, Roberts JM. Association of periconceptional multivitamin use and risk of preterm or small-for-gestational-age births. Am J Epidemiol. 2007 Aug 1;166(3):296-303. doi: 10.1093/aje/kwm071. Epub 2007 May 11.

    PubMed 17496313

  • Czeizel AE, Dudas I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992 Dec 24;327(26):1832-5. doi: 10.1056/NEJM199212243272602.

    PubMed 1307234

  • Ingrid Goh Y, Bollano E, Einarson TR, Koren G. Prenatal multivitamin supplementation and rates of congenital anomalies: a meta-analysis. J Obstet Gynaecol Can. 2006 Aug;28(8):680-689. doi: 10.1016/S1701-2163(16)32227-7.

    PubMed 17022907

  • Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet. 1991 Jul 20;338(8760):131-7.

    PubMed 1677062

  • Bortolus R, Blom F, Filippini F, van Poppel MN, Leoncini E, de Smit DJ, Benetollo PP, Cornel MC, de Walle HE, Mastroiacovo P; Italian and Dutch folic acid trial study groups. Prevention of congenital malformations and other adverse pregnancy outcomes with 4.0 mg of folic acid: community-based randomized clinical trial in Italy and the Netherlands. BMC Pregnancy Childbirth. 2014 May 13;14:166. doi: 10.1186/1471-2393-14-166.

    PubMed 24884885

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing folic acid in people with Congenital Malformations, run by Azienda Ospedaliera Universitaria Integrata Verona at 34 sites in Italy.

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 19 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: status not confirmed, as of the sponsor's last update on 14 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 34 sites in Italy. 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?

Results are not available in the source record.

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?

number of congenital malformations (time frame: 112 weeks). 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 NCT01244347, which also lists 8 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 14 Jan 2015.

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