Preterm BirthEarly Phase 1NCT02536352
Effect of Supplementation of Fluoride on Maternal Periodontal Health, Preterm Delivery, and Perinatal Well-Being
A Early Phase 1 study testing Prenatal vitamin-mineral containing 3 mg fluoride and Prenatal vitamin-mineral containing 0 mg fluoride in people with Preterm Birth and Preterm Labor, run by Johns Hopkins University at 1 site in United States.
Trial summary
The purpose of this study is to determine whether fluoride supplementation during pregnancy is effective in extending the length of gestation and improving overall perinatal well-being. Read more about this study
- Who is it for?
- Ages 18 to 55 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Birth, Preterm Labor, Bacteremia
- What is being tested?
- Prenatal vitamin-mineral containing 3 mg fluoride and Prenatal vitamin-mineral containing 0 mg fluoride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 43 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to 1 Oct 2019
- Phase
- Early Phase 1
- 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 55 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Women who are between 10-20 weeks gestational age at the time of recruitment
- Delivery at Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center
Who cannot join
- Use of prescription strength, high dose fluoride products (greater than 0.76% of fluoride), prescribed by a dental professional (toothpastes, mouthwashes, topical treatments). All over-the-counter toothpaste and mouthwash products are acceptable to use.
- Occupational exposure to fluoride.
- The daily amount of fluoride ingested should not exceed 10 mg/day, according to the Institute of Medicine and the FDA. Any participants consuming amounts of fluoride close to 10 mg/day will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
The purpose of this study is to determine whether fluoride supplementation during pregnancy is effective in extending the length of gestation and improving overall perinatal well-being.
Read the detailed description
The Centers for Disease Control and Prevention (CDC) reports that preterm birth affected about 1 in 10 infants born in the United States in 2015. These statistics emphasize the significance of implementing a safe and effective therapy into routine clinical care aimed at reducing the rate of preterm birth. There has been evidence to suggest that fluoride supplementation to women during pregnancy can provide other medical benefits, in addition to a reduction in dental caries.
Fluoride is recognized by the Food and Nutrition Board (F\&NB) of the American Academy of Sciences and the Food \& Drug Administration (FDA) as an essential ion due to its association with a reduction in dental caries.
Upon entering the body, fluoride is taken up into the bones/calcified tissues, and excreted by the kidneys. When supplied during pregnancy in small aliquots, as with water fluoridation, the fluoride is likely taken up in the mother's bones and excreted by her kidneys so rapidly, that the fetus is denied a meaningful amount of fluoride, unless it is supplied in a pulse dose by supplement. The Institute of Medicine's Food and Nutrition Board recommends 3 mg/day for Adequate Intake in pregnancy and deems 10 mg/day as the Upper Limit.
After several papers elucidating an association between poor dentition, periodontal disease, and preterm birth, subsequent RCT's of regular periodontal scaling and treatment during pregnancy are still inconclusive in regards to preterm birth.
The investigators hypothesize that fluoride supplementation during pregnancy may have a beneficial effect on the natural microbiome of the maternal oral cavity and genital tract, capable of protecting against transient bacteremia and ascending infection, respectively, which are known antecedents to both preterm labor and preterm premature rupture of membranes. The research team predicts that the testing and analysis of specimens collected will demonstrate microbiome changes toward a more favorable profile not associated with preterm birth.
The proposed randomized, double-blinded, placebo-controlled clinical trial aims to confirm the efficacy of fluoride supplementation in pregnancy to extend length of gestation and increase overall perinatal well-being, and to confirm transplacental transfer of supplemental fluoride. This research may also identify other beneficial maternal and neonatal outcomes associated with the administration of fluoride during the perinatal period by attempting to characterize and compare the microbiomes of the maternal oral cavity and genital tracts between supplemented and unsupplemented gravidas.
- Being tested
- Prenatal vitamin-mineral containing 3 mg fluoride, Prenatal vitamin-mineral containing 0 mg fluoride
- Keywords
- Fluoride Supplementation, Prenatal Vitamin, Pregnancy Nutrition, Prenatal Nutrition
- Medical subject headings
- Premature Birth, Obstetric Labor, Premature, Bacteremia, Fetal Membranes, Premature Rupture
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Prenatal vitamin-mineral containing 3 mg fluorideDrug
Prenatal vitamin-mineral containing 3 mg fluoride to be taken daily, starting at 10-20 weeks gestation until delivery.
Prenatal vitamin-mineral containing 0 mg fluorideDietary supplement
Prenatal vitamin-mineral containing 0 mg fluoride to be taken daily, starting at 10-20 weeks gestation until delivery.
| Study group | Role | What they receive |
|---|---|---|
| Fluoride prenatal vitamin | Experimental | Prenatal vitamin-mineral containing 3 mg fluoride Receives: Drug: Prenatal vitamin-mineral containing 3 mg fluoride |
| Standard prenatal vitamin | Active comparator | Prenatal vitamin-mineral containing 0 mg fluoride Receives: Dietary Supplement: Prenatal vitamin-mineral containing 0 mg fluoride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Length of gestation
the length of gestation will be measured in weeks at time of delivery
Measured: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Secondary outcomes (4)
Birth weight
Birth weight will be measured in grams and pounds
Measured: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Birth length
birth length will be measured in inches
Measured: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Preterm birth
Preterm birth will be measured in weeks at time of delivery
Measured: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Preterm premature rupture of membranes (PPROM)
PPROM will be measured in weeks at time of PPROM
Measured: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2015 (estimated)
- Study startOct 2015
- Primary completion1 Oct 2019
- Study completion1 Oct 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Preterm BirthStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Irina Burd, M.D., Ph.D., Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02536352
- Sponsor's protocol ID
- IRB00038838
- Status last verified
- Nov 2019
- First submitted
- 27 Aug 2015
- Last updated
- 5 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Leverett DH, Adair SM, Vaughan BW, Proskin HM, Moss ME. Randomized clinical trial of the effect of prenatal fluoride supplements in preventing dental caries. Caries Res. 1997;31(3):174-9. doi: 10.1159/000262394.
PubMed 9165186Srinivas SK, Sammel MD, Stamilio DM, Clothier B, Jeffcoat MK, Parry S, Macones GA, Elovitz MA, Metlay J. Periodontal disease and adverse pregnancy outcomes: is there an association? Am J Obstet Gynecol. 2009 May;200(5):497.e1-8. doi: 10.1016/j.ajog.2009.03.003.
PubMed 19375568Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US); 1997. Available from http://www.ncbi.nlm.nih.gov/books/NBK109825/
PubMed 23115811Iheozor-Ejiofor Z, Middleton P, Esposito M, Glenny AM. Treating periodontal disease for preventing adverse birth outcomes in pregnant women. Cochrane Database Syst Rev. 2017 Jun 12;6(6):CD005297. doi: 10.1002/14651858.CD005297.pub3.
PubMed 28605006
Study at a glance
From the registry record, last updated by the sponsor on 5 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Supplementation of Fluoride on Maternal Periodontal Health, Preterm Delivery, and Perinatal Well-Being
- ClinicalTrials.gov ID
- NCT02536352
- Acronym / sponsor ID
- IRB00038838
- Keywords
- Fluoride Supplementation, Prenatal Vitamin, Pregnancy Nutrition, Prenatal Nutrition
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- 1 Oct 2019 (actual)
- Study completion
- 1 Oct 2019 (actual)
- First posted
- 31 Aug 2015 (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 determine whether fluoride supplementation during pregnancy is effective in extending the length of gestation and improving overall perinatal well-being.
Detailed description
The Centers for Disease Control and Prevention (CDC) reports that preterm birth affected about 1 in 10 infants born in the United States in 2015. These statistics emphasize the significance of implementing a safe and effective therapy into routine clinical care aimed at reducing the rate of preterm birth. There has been evidence to suggest that fluoride supplementation to women during pregnancy can provide other medical benefits, in addition to a reduction in dental caries.
Fluoride is recognized by the Food and Nutrition Board (F\&NB) of the American Academy of Sciences and the Food \& Drug Administration (FDA) as an essential ion due to its association with a reduction in dental caries.
Upon entering the body, fluoride is taken up into the bones/calcified tissues, and excreted by the kidneys. When supplied during pregnancy in small aliquots, as with water fluoridation, the fluoride is likely taken up in the mother's bones and excreted by her kidneys so rapidly, that the fetus is denied a meaningful amount of fluoride, unless it is supplied in a pulse dose by supplement. The Institute of Medicine's Food and Nutrition Board recommends 3 mg/day for Adequate Intake in pregnancy and deems 10 mg/day as the Upper Limit.
After several papers elucidating an association between poor dentition, periodontal disease, and preterm birth, subsequent RCT's of regular periodontal scaling and treatment during pregnancy are still inconclusive in regards to preterm birth.
The investigators hypothesize that fluoride supplementation during pregnancy may have a beneficial effect on the natural microbiome of the maternal oral cavity and genital tract, capable of protecting against transient bacteremia and ascending infection, respectively, which are known antecedents to both preterm labor and preterm premature rupture of membranes. The research team predicts that the testing and analysis of specimens collected will demonstrate microbiome changes toward a more favorable profile not associated with preterm birth.
The proposed randomized, double-blinded, placebo-controlled clinical trial aims to confirm the efficacy of fluoride supplementation in pregnancy to extend length of gestation and increase overall perinatal well-being, and to confirm transplacental transfer of supplemental fluoride. This research may also identify other beneficial maternal and neonatal outcomes associated with the administration of fluoride during the perinatal period by attempting to characterize and compare the microbiomes of the maternal oral cavity and genital tracts between supplemented and unsupplemented gravidas.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fluoride prenatal vitamin | Experimental | Drug: Prenatal vitamin-mineral containing 3 mg fluoridePrenatal vitamin-mineral containing 3 mg fluoride |
| Standard prenatal vitamin | Active comparator | Dietary Supplement: Prenatal vitamin-mineral containing 0 mg fluoridePrenatal vitamin-mineral containing 0 mg fluoride |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Women who are between 10-20 weeks gestational age at the time of recruitment
- Delivery at Johns Hopkins Hospital or Johns Hopkins Bayview Medical Center
Key exclusion criteria (3 listed)
- Use of prescription strength, high dose fluoride products (greater than 0.76% of fluoride), prescribed by a dental professional (toothpastes, mouthwashes, topical treatments). All over-the-counter toothpaste and mouthwash products are acceptable to use.
- Occupational exposure to fluoride.
- The daily amount of fluoride ingested should not exceed 10 mg/day, according to the Institute of Medicine and the FDA. Any participants consuming amounts of fluoride close to 10 mg/day will be excluded.
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 |
|---|---|---|
| Prenatal vitamin-mineral containing 3 mg fluoridePrenatal vitamin-mineral containing 3 mg fluoride to be taken daily, starting at 10-20 weeks gestation until delivery. | Drug | Fluoride prenatal vitamin |
| Prenatal vitamin-mineral containing 0 mg fluoridePrenatal vitamin-mineral containing 0 mg fluoride to be taken daily, starting at 10-20 weeks gestation until delivery. | Dietary supplement | Standard prenatal vitamin |
Primary outcome
Length of gestation
Time frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
the length of gestation will be measured in weeks at time of delivery
4 secondary outcomes
Birth weight
Time frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Birth length
Time frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Preterm birth
Time frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
Preterm premature rupture of membranes (PPROM)
Time frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study
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 5 Nov 2019.
- Background: PubMed 9165186Leverett DH, Adair SM, Vaughan BW, Proskin HM, Moss ME. Randomized clinical trial of the effect of prenatal fluoride supplements in preventing dental caries. Caries Res. 1997;31(3):174-9. doi: 10.1159/000262394.
- Background: PubMed 19375568Srinivas SK, Sammel MD, Stamilio DM, Clothier B, Jeffcoat MK, Parry S, Macones GA, Elovitz MA, Metlay J. Periodontal disease and adverse pregnancy outcomes: is there an association? Am J Obstet Gynecol. 2009 May;200(5):497.e1-8. doi: 10.1016/j.ajog.2009.03.003.
- Background: PubMed 23115811Institute of Medicine (US) Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington (DC): National Academies Press (US); 1997. Available from http://www.ncbi.nlm.nih.gov/books/NBK109825/
- Background: PubMed 28605006Iheozor-Ejiofor Z, Middleton P, Esposito M, Glenny AM. Treating periodontal disease for preventing adverse birth outcomes in pregnant women. Cochrane Database Syst Rev. 2017 Jun 12;6(6):CD005297. doi: 10.1002/14651858.CD005297.pub3.
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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.
Irina Burd, M.D., Ph.D. principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Prenatal vitamin-mineral containing 3 mg fluoride and Prenatal vitamin-mineral containing 0 mg fluoride in people with Preterm Birth and Preterm Labor, run by Johns Hopkins University 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 3 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 5 Nov 2019. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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?
Length of gestation (time frame: Participants will be followed from the time of study enrollment until delivery, up to 30 weeks total in the study). 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 NCT02536352, which also lists 4 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 5 Nov 2019.