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WithdrawnNCT03291327Updated Mar 7, 2018

Evaluation of Two Active Lactobacilli for the Maintenance of Gingival Health

An interventional study of Probiotics in Gingivitis, sponsored by Queen Mary University of London. Withdrawn. Open to participants aged 18 Years to 30 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-03-07.

Sponsored by Queen Mary University of London · Not applicable, Interventional, and Prevention

Why this study was withdrawn
Due to recruitment issues
Phase
Not applicable
Study type
Interventional
Enrollment
0
Allocation
Randomized
Ages
18 Years to 30 Years
Sex
All
01

Study summary

The objective of the study will be to demonstrate the effects of two active lactobacilli (A/B) and determine whether there are any changes in plaque accumulation, gingival health, immunological and microbial markers compared to a placebo (P) over a 2-week period of refraining from normal oral hygiene practice. This is a single centre, randomised, double-blind, parallel group study (3-Arm) of healthy subjects aged 18-30 years designed to demonstrate the effectiveness of two active lactobacilli using the experimental gingivitis Model: A proof of principle study on plaque, gingival status, immunological and microbial markers compared to placebo.

Read the detailed description

This is a single centre, randomised, double-blind, parallel group study (3-Arm) of healthy subjects aged 18-30 years designed to demonstrate whether two active lactobacilli in the Experimental Gingivitis Model modify plaque accumulation, gingival status, immunological and microbial markers compared to placebo. Participants will be screened at a pre-baseline visit by a Study Dentist to determine their suitability for the study which will include healthy volunteers and exclude subjects with initial signs of gingival inflammation. Those volunteers considered to be suitable for the study will receive a pre-baseline dental prophylaxis. Participants will be required to return to the Study Centre 14 days following the screening visit and volunteers who comply with all the inclusion and exclusion criteria will be randomly allocated to one of three treatment groups at the baseline visit. Two of the groups will receive one of two probiotics containing either Lactobacillus (A) or Lactobacillus (B). The third group will receive placebo (P) which does not contain any active ingredient. Each subject will receive a fluoride toothpaste (Colgate Regular) and toothbrush (Oral-B) at the pre-baseline visit to reduce any carry-over (anti-microbial) effects from their normal toothpaste usage.

The initial brushing with the gum shield in place will be conducted under supervision by the study staff at the study centre to enable participants to be familiar with using the gum shield during their unsupervised brushing at home. Each participant will be given both verbal and written instructions, to enable them to correctly insert the gum shield under supervision; the placement of the gum shield will be checked by a study staff member, followed by supervised brushing of the upper teeth.

At the baseline visit those participants who fulfil the inclusion/exclusion criteria will receive a fluoride toothpaste (Colgate Regular) and toothbrush (Oral-B) for use throughout the duration of the study. All treatments will be unsupervised at the subject's home. Participants will be provided with a participant diary at the screening visit to check for compliance with tooth brushing throughout the study period. At the baseline visit those volunteers who successfully completed the inclusion/exclusion criteria will continue to complete the participant diary for compliance with twice daily tooth brushing, the test and control products and the placement of the gum shield over the lower teeth when brushing the upper teeth during the study. Those participants who fail to satisfy the inclusion/exclusion criteria will return the diary together with the fluoride toothpaste and toothbrush at the baseline visit.

Participants will be instructed to abstain from all methods of tooth cleaning in the lower (mandible) jaw for two weeks apart from the fluoride toothpaste provided by the study centre. A soft acrylic stent (gum shield) will be fabricated to cover the teeth in the lower jaw (mandible) whilst brushing the teeth in the upper (maxilla) jaw and will be removed 10 minutes after brushing. The soft stent can be easily inserted and removed without disturbance of the developing plaque whilst ensuring participants do not brush their lower teeth and thus disrupt plaque formation. Modified Gingival Index (MGI) (Lobene et al. 1986) assessments will be undertaken prior to the other assessments as this is non-invasive assessment. At baseline and after two weeks (+ 14 days) four sites/tooth (mesial, mid-buccal, distal and lingual) will be probed using the Gingival Bleeding Index [GBI]) as defined by Saxton \& van der Ouderaa (1989) to assess the health status of the gingiva. Probing following one week of plaque accumulation will be avoided as bleeding in the gingival crevice may influence the developing biofilm. Non-invasive samples of gingival crevicular fluid (GCF) will however, be collected at all-time intervals before the BOP measurements or plaque sampling as the volume of GCF (Kistler et al. 2013) has been shown to increase before the development of clinically evident inflammation e.g. GBI. The GCF samples will be collected from the mesio-buccal sites of 4 selected sites (two teeth in each quadrant of the lower [mandible] jaw) on perio strips (ProFlow Inc. Amityville, NY) (Thunell et al. 2010). The strip will be applied in the gingival sulcus for 30 seconds to collect a standardised GCF fluid sample. The GCF samples will be pooled from 4 sites of each participant as indicated above at each time point and analysed on an individual basis. The number of sites with clearly visible plaque following the disclosing of the teeth in the lower (mandible) jaw (modified Quigley-Hein) (Turesky et al. 1970) will be recorded. Plaque will be collected from the buccal and lingual surfaces of teeth in the lower (mandible) jaw excluding 3rd molars from each participant using a sterile curette and placed in tubes with saturated saline-DMSO buffer. The plaque samples, and GCF samples in tubes with Phosphate Buffered Saline (PBS), will be transported on dry ice and stored at -80°C. All assessments and sample collection will be undertaken by trained and calibrated personnel. After two weeks, all participants who complete the study will receive a dental prophylaxis following the collection of samples and will be asked to resume their normal oral hygiene regime.

02

Conditions studied

  • Gingivitis

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03

Who can participate

Ages eligible
18 Years to 30 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  1. Informed Consent Demonstrates understanding of the study and willingness to participate as evidenced by voluntary written informed consent and has received a signed and dated copy of the informed consent form.
  2. Age Aged 18-30 years.
  3. Compliance Understands and is willing, able and likely to comply with all study procedures and restrictions.
  4. General Health Healthy volunteer

    Good general and mental health, in the opinion of the investigator or medically qualified designee:

    No clinically significant and relevant abnormalities of medical history or physical and oral examination.

    Absence of any condition that would impact on the subject's safety, or wellbeing, or affect the individual's ability to understand the study procedures and requirements.

  5. Contraception Females of childbearing potential who are, in the opinion of the investigator, practising a reliable method of contraception. To exclude any confounding effects of pregnancy related changes in dental health. Adequate contraception is defined as abstinence, oral contraceptive, either combined or progestogen alone OR injectable progestogen OR implants of levonorgestrel OR estrogenic vaginal ring OR percutaneous contraceptive patches OR intrauterine device or intrauterine system OR double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] plus spermicidal agent [foam, gel, film, cream, suppository]) OR male partner sterilization prior to the female subject's entry into the study, and this male is the sole partner for that subject. Following consent, Females will be required to use a pregnancy test kit administered at the study centre at Visit 1, results will be recorded on the relevant Case Report Form (CRF) and treated in confidence.
  6. Dental Requirements At least eight teeth in the lower jaw with a minimum of 4 teeth in each quadrant BPE scores 0-2 in the lower (mandible) jaw Bleeding Score of \<15% of sites in the lower (mandible) jaw (BOP) Following the dental prophylaxis, participants should have little or no gingival inflammation (\<1) in the lower (mandible) jaw as assessed by MGI.
  7. General Requirement Agree not to consume any other probiotic or yoghurt products during the study. Agree not to chew chewing gum during the study.

Exclusion criteria

Exclusion Criteria:

  1. Any inclusion criteria not met
  2. Any disease which in the investigator's opinion could affect the participant's response to treatment, including in particular:

    • Diabetes mellitus Type I and II
    • Presence or recent history of infectious diseases such as AIDS, Hepatitis and tuberculosis or other respiratory infections including those that can be transmitted in saliva.
    • Bronchitis, tonsillitis or sinusitis.
  3. Substance abuse e.g. smoking or chewing of tobacco or paan, drugs and alcoholism. E-cigarettes will also be excluded
  4. Recent use of antibiotics and/or anti-inflammatory medication (within 4 weeks of visit).
  5. Women who are known to be pregnant or who are intending to become pregnant over the duration of the study.
  6. Allergy/Intolerance to the test and placebo products (ingredients) in particular lactose and milk protein content (allergens) in the test products.
  7. Evidence of chronic periodontitis (BPE score >3 in any sextant of the lower jaw)
  8. Bleeding Score of >15% of sites in the lower (mandible) jaw
  9. MGI Score of >1 (mean) in the lower (mandible) jaw
  10. Currently ongoing treatment for chronic periodontitis
  11. Currently using an anti-microbial mouth rinse
  12. Participation in another clinical study or receipt of an investigational drug within 60 days of the screening visit.
  13. Previous participation in this study.
  14. Clinical dental students (2-5 years) will be excluded.
  15. Ongoing or planned elective dental treatment involving endodontic treatment and crown and bridge preparation.

Furthermore, any participant requiring to undergo any emergency dental treatment during the study period will be assessed to determine whether they should continue to participate or be excluded.

04

Study design

Phase
Not applicable
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
0 participants (actual)

Study arms

  • Active comparator
    Investigational product (Lactobacillus A)

    All volunteers considered to be suitable for the study will receive a pre-baseline dental prophylaxis. At baseline (BL) they will be instructed to abstain from all methods of tooth cleaning in mandible for 2 weeks (2W) apart from the fluoride toothpaste provided. A soft gum shield provided will cover the mandibular teeth whilst brushing and will be removed 10 minutes after brushing. Gingival health assessments and gingival crevicular fluid (GCF) and bacterial plaque samples be undertaken at BL and 2W. At 2W, all participants will receive a dental prophylaxis following the collection of samples and will be asked to resume their normal oral hygiene regime. Lactobacillus (A) in the form of a lozenge to be taken twice daily (in the morning and in the evening). The lactobacilli will be in the form of a lozenge, which should be placed on the tongue and allowed to dissolve. Any undissolved particles may be swallowed by the participant.

    Dietary Supplement: Probiotics

  • Active comparator
    Investigational product (Lactobacillus B)

    All volunteers considered to be suitable for the study will receive a pre-baseline dental prophylaxis. At baseline (BL) they will be instructed to abstain from all methods of tooth cleaning in mandible for 2 weeks (2W) apart from the fluoride toothpaste provided. A soft gum shield provided will cover the mandibular teeth whilst brushing and will be removed 10 minutes after brushing. Gingival health assessments and gingival crevicular fluid (GCF) and bacterial plaque samples be undertaken at BL and 2W. At 2W, all participants will receive a dental prophylaxis following the collection of samples and will be asked to resume their normal oral hygiene regime. Lactobacillus (B) in the form of a lozenge to be taken twice daily (in the morning and in the evening). The lactobacilli will be in the form of a lozenge, which should be placed on the tongue and allowed to dissolve. Any undissolved particles may be swallowed by the participant.

    Dietary Supplement: Probiotics

  • Placebo comparator
    Placebo Product (P)

    All volunteers considered to be suitable for the study will receive a pre-baseline dental prophylaxis. At baseline (BL) they will be instructed to abstain from all methods of tooth cleaning in mandible for 2 weeks (2W) apart from the fluoride toothpaste provided. A soft gum shield provided will cover the mandibular teeth whilst brushing and will be removed 10 minutes after brushing. Gingival health assessments and gingival crevicular fluid (GCF) and bacterial plaque samples be undertaken at BL and 2W. At 2W, all participants will receive a dental prophylaxis following the collection of samples and will be asked to resume their normal oral hygiene regime. Placebo (P) in the form of a lozenge to be taken twice daily (in the morning and in the evening). The placebo will be in the form of a lozenge, which should be placed on the tongue and allowed to dissolve. Any undissolved particles may be swallowed by the participant.

    Dietary Supplement: Probiotics

Interventions

  • Dietary supplementProbiotics

    Lozenges for Home use

05

What researchers measure

Primary outcomes

  1. Changes in gingival health status as indicated by changes in Gingival Bleeding Index (GBI)

    Changes in the gingival health status following the application of each test product will be performed using validated tools namely bleeding on probing (GBI) on test group subjects compared to placebo subjects. The presence or absence of bleeding will be scored within 30 seconds after probing with a Williams periodontal probe. Score Description 0 Absence of bleeding after 30 seconds. 1. Bleeding observed after 30 seconds. 2. Immediate bleeding observed.

    Time frame: Baseline to +14 days

  2. Changes in gingival health status as indicated by changes in Quigley-Hein Plaque Index (Q-H)

    Changes in the gingival health status following the application of each test product will be performed using assessment of plaque accumulation (Q-H) on test group subjects compared to placebo subjects. All teeth in mandible excluding third molars will be scored with Quigley-Hein Plaque Index (Q-H). The teeth will be lightly dried a disclosing solution (PlaqueSearch TePe® TePe Munhygienprodukter, Malmo, Sweden) will be applied to all teeth in the mandible jaw. All teeth in the lower (mandible) jaw excluding 3rd molars will be visually scored using the Index, both buccal and lingual aspects of each tooth will be assessed. Score Description 0 No plaque. 1. Isolated areas of plaque at gingival margin. 2. Thin band of plaque at gingival margin (\< 1mm). 3. Plaque covering up to 1/3 of tooth surface. 4. Plaque covering 1/3 to 2/3 of tooth surface. 5. Plaque covering \> 2/3 of tooth surface.

    Time frame: Baseline to +14 days

  3. Changes in gingival health status as indicated by changes in Modified Gingival Index (MGI)

    Changes in the gingival health status following the application of each test product will be performed using colour changes in the gingiva (MGI) of test group subjects compared to placebo subjects. All teeth in mandible excluding third molars will be scored with MGI Score Description 0 Absence of inflammation. 1. Mild inflammation; slight change in colour, little change in texture of any portion of but not the entire marginal or papillary gingival unit. 2. Mild inflammation; criteria as above but involving the entire marginal or papillary gingival unit. 3. Moderate inflammation; glazing, redness, oedema, and/or hypertrophy of the marginal or papillary gingival unit. 4. Severe inflammation; marked redness, oedema and/or hypertrophy of the marginal or papillary gingival unit, spontaneous bleeding, congestion or ulceration.

    Time frame: Baseline to +14 days

Secondary outcomes

  1. Changes in Inflammatory Markers

    To assess changes in inflammatory markers in Gingival Crevicular Fluid following use of each test product

    Time frame: Baseline to + 14 days

  2. Changes in Bacterial Composition

    To assess changes in bacterial composition in collected plaque samples following use of each test product

    Time frame: Baseline to + 14 days

06

Study locations

No study locations are listed for this record.

07

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

08

Registry details

Key details

Study ID
NCT03291327
Lead sponsor
Queen Mary University of London
Collaborators
Symrise AG
Responsible party
Sponsor
First posted
Sep 25, 2017
Start date
Mar 2018 (estimated)
Primary completion
Oct 2018 (estimated)
Completion
Oct 2018 (estimated)
Last update
Mar 7, 2018

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is withdrawn, as verified in Aug 2017. You cannot join it, but the record below documents what was studied.

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