Anti plaque/gingivitis efficacy of two toothpastes
Research type
Research Study
Full title
A study to measure the efficacy of a toothpaste containing 2% zinc citrate, 0.5% curcumin and micronutrients on gingival condition and supra-gingival plaque over a period of 14 weeks compared to a toothpaste containing 0.3% triclosan
IRAS ID
123862
Contact name
Iain Chapple
Contact email
Sponsor organisation
Unilever
Research summary
Lay Summary of Results
Executive Summary
The below clinical report documented on pages 3-7 was prepared on 22nd October 2013 at the completion of the clinical phase of the study. All study activities ceased at the study site on 18th September 2014. Data was analysed by the study statistician at Unilever Port Sunlight and shared with the PI on 8th December 2014. Due to the confidential nature of the study and the intellectual property and patent filing by the sponsor, the clinical outcomes for the novel test product containing Curcumin 0.5% + 2% Zinc Citrate Trihydrate, tested against a positive control paste (Colgate Total) were not published as part of the below report. This summary is to fulfil the requirements of REC conditions of approval, but providing a high-level overview of the clinical outcomes (not reported in the below report as data had not been analysed at the time) within this executive summary, and to share the detailed clinical study report from 22nd October 2013.
The primary objective of the study was to measure the efficacy of a novel test toothpaste containing 2% zinc citrate trihydrate, 0.5% curcumin and micronutrients on improving the gingival condition and reducing supra-gingival plaque over a period of 15 weeks compared to a toothpaste containing 0.3% Triclosan (Colgate Total).
The test toothpaste out performed the Colgate Total positive control paste for reducing measures of gingival inflammation measured as the Modified Gingival Index and the gingival bleeding score. The same was true for reductions in plaque index (Quigley Hein Plaque Index). The results were statistically significant for these primary outcomes.
There were no major adverse events, or serious incidents. One patient developed a delayed hypersensitivity reaction to the test paste in the form of Erythema Multifome (see report). This was diagnosed by the PI, the patient withdrawn from the study and reviewed 1 week later, when the condition had resolved. Study volunteers did observe that the test toothpaste colour (yellow due to the curcumin) stained sinks and clothes, and this was deemed to be a disadvantage and a likely barrier to the development of the formulation into a commercial product.
To date, the sponsor has not developed or marketed a product based around the test formulation, despite the positive clinical outcomes.
Contacts
SPONSOR
Unilever Research and Development Port Sunlight,
Quarry Road East
Bebington
Wirral
CH63 3JW
Sponsor Contact
Julie Nicholson
Tel: 0151 641 3677
Fax: 0151 641 1889
MONITOR
Unilever Research and Development Port Sunlight,
Quarry Road East
Bebington
Wirral
CH63 3JW
PRINCIPAL INVESTIGATOR
Professor Iain Chapple
Periodontal Research Group,
The University of Birmingham;
School of Dentistry;
Birmingham B4 6NN;
UK;
Tel: 0121 4665129
Fax: 0121 4665661
STUDY DENTIST
Dr Mike Milward
Periodontal Research Group,
The University of Birmingham;
School of Dentistry;
Birmingham B4 6NN;
UK;
Tel: 0121 4665132
Fax: 0121 4665661
REPORTING EXPEDITED ADVERSE EVENTS
Dr Mike Milward
Periodontal Research Group,
The University of Birmingham;
School of Dentistry;
Birmingham B4 6NN;
UK;
Tel: 0121 4665132
Fax: 0121 4665661
OTHER INSTITUTIONS
Analysis of GCF Samples - Unilever Vlaardingen
1.0 Rationale for Study
The study was conducted to provide in vivo efficacy data for the curcumin containing toothpaste. The data will form part of the claim support dossier.
2.0 Study Objectives
2.1 Primary Objective
The primary objective of the study was to measure the efficacy of a toothpaste containing 2% zinc citrate trihydrate, 0.5% curcumin and micronutrients on improving the gingival condition and reducing supra-gingival plaque over a period of 15 weeks compared to a toothpaste containing 0.3% Triclosan (Colgate Total).
2.2 Secondary Objective
The secondary objective of the study was to evaluate the effect on biochemical parameters of toothpaste containing 2% zinc citrate trihydrate, 0.5% curcumin and micronutrients over a period of 15 weeks compared to a toothpaste containing 0.3% Triclosan (Colgate Total).
2.3 Tertiary Objective(s)
The tertiary objective of the study was to evaluate the effect on the subgingival microbiome of toothpaste containing 2% zinc citrate trihydrate, 0.5% curcumin and micronutrients over a period of 15 weeks compared to a toothpaste containing 0.3% Triclosan (Colgate Total).
3.0 Study Outline
The study was conducted according to the study protocol (Version 4.0, 22nd February 2013). This brief report summarises the consent and enrolment statistics, along with withdrawals and failed completions. It also reports any adverse events and how these were followed up. The report does not present clinical outcomes or biological outcomes since these are currently under analysis by Unilever.
3.1 Assessments at Each Visit
All assessments planned for each study visit are presented in Table 1.
Table 1. Time and Event Schedule
Visit 1
(Run-In Phase)
Visit 2
(Test phase
Week 0)
Visit 3
(Test Phase
Week 7)
Visit 4
(Test Phase
Week 14)
Refrain from all oral hygiene on morning of test visit
X
X
x
X
Informed Consent
X
Medical History Collection / Review
X
X
x
X
Soft Tissue & BPE Assessment
X
X
x
X
MGI Assessment
X
X
x
X
BI Assessment
X
X
x
X
Plaque Assessment
X
X
x
X
GCF Sampling
X
X
Supragingival plaque sampling (weighed)
X
X
X
Subgingival plaque sampling (weighed)
X
X
X
Issue of Run-In toothpaste and toothbrush
X
Collection of Run-In toothpaste - weight
X
Issue of test product and toothbrush
X
x (if required)
Collection of test product - weight
X
AE Recording
X
x
X
Remuneration
x*
X
*those volunteers not meeting the inclusion criteria
4. Study Products
4.1 Presentation and Administration
The principal constituents of the test and control tooth pastes, as well as the “wash out” or “run in” paste are documented in Table 2.
Table 2. Time and Event Schedule
Description
No of Tubes
Actives
Supplied by
Test paste 1
Toothpaste containing 0.5% curcumin and 2% Zinc Citrate Trihydrate
240
0.32% NaF, 1% α-tocopheryl acetate; 2% ascorbyl phosphate; 0.5% curcumin; 2% zinc citrate trihydrate
GTC Casale
Test Paste 2
Colgate Total.
240
0.32% NaF
0.3% Triclosan
Italian Commercial Product
Run-in Toothpaste
Silica toothpaste
240
0.22% NaF
GCT Casale
Test toothpaste 1 was supplied in plain white laminate tubes and labeled accordingly.
Test toothpaste 2 was supplied in its commercial packaging and over wrapped and labeled. The Colgate Total used in this study will be purchased in Italy prior to shipping to the UK.
The run-in toothpaste was supplied in plain white laminate tubes and labeled accordingly.
Soft Signal/Pepsodent toothbrushes were supplied in their commercial packaging.
5.0 Ethical Approval and R&D Approval
The study was approved by the NRES London-Surrey Borders Research Ethics Committee on 27th March 2013 (13/LO/0405), having been cleared by the MHRA as not requiring their approval. R&D approval was provided by Birmingham Community Healthcare Trust (BCHCDent319.123862).
6.0 Sponsorship
Unilever acted as sponsor for the study.
7.0 Study Conduct and Performance Outcomes
The study commenced on 7th May 2013. 109 volunteers were consented to take part in the study and screened for suitability according to inclusion and exclusion criteria. After examination by Dr M Milward 91 volunteers were enrolled to take part, the remaining 18 did not fulfil inclusion/exclusion criteria.
Table 3 documents details of the 8 volunteers withdrawn across the duration of the study. Three volunteers were lost at screening leaving 88 who attended the baseline sessions. Three volunteers were withdrawn at/or after baseline leaving 85 who attended the 7wk review sessions. A further two volunteers were withdrawn at / or after the 7wk review appointment leaving 83 volunteers who attended the final review sessions. The details of the reasons for withdrawals are documented in Table 3.
Table 3 – Withdrawn Volunteers
Volunteer no
Date With Drawn
Last Data Collection
Reasons
058
28 May 2013
Screening
Volunteer did not use wash out products as instructed.
085
10 June 2013
Screening
Volunteer wished to withdraw.
024
13 June 2013
Screening
Volunteer unable to make further appointments.
055
21 June 2013
Baseline
Volunteer concerned with staining.
032
25 June 2013
Baseline
Volunteer reported experiencing sickness due to toothpaste.
051
16 July 2013
Baseline
Volunteer hospitalized due to unrelated illness.
013
18 July 2013
7wk Review
Volunteer discovered she was pregnant.
004
16 August 2013
7wk Review
Volunteer suffered Adverse Event due to product. (Please see 7.1 AE below).
Table 4 documents details of one volunteer (015) who was unable to attend all of the sampling sessions, but who remained in the study as the 7-week review that was missed is unlikely to have affected study outcomes. A further seven volunteers who breached the inclusion criteria after enrolment are also documented. These volunteers were happy to remain in the study and so their full data was recorded. The recommendation is that Unilever analyse the data with and without these volunteers. If there is no difference in outcome then the volunteers could be left in, if there is a difference then they would need to be left out. This would then require a post-hoc power calculation to ensure the power of the study was not compromised.
Table 4 – Potentially Compromised Volunteers
Volunteer no
Reasons
Note to file number
015
Volunteer did not attend 7 week review appointment.
001
041
Volunteer prescribed a course of antibiotics - Metronidazole 200mg from 30th May to 2nd June 2013
002
035
Volunteer prescribed NSAD – Mefenamic Acid 500mg, taken for 2 days starting on 27th May – 28th May 2013
003
037
Volunteer prescribed course of antibiotics – Nitrofurantion 50mg for 3days, from 22nd May – 24th May 2013
004
074
Volunteer prescribed a course of antibiotics – Phenoxymethylpenicillin 250mg for 8 days, from 21st May – 28th May 2013
005
014
Volunteer prescribed a course of antibiotics – Eyrthromycin 200mg for 7days during July 2013
009
003
Volunteer prescribed long term use of Ibuprofen & Co-dydramol as of 12th July 2013 for back pain.
010
071
Volunteer prescribed a course of antibiotics – Amoxil 250mg for 7 days, from 1st August – 7th August
011
7.1 Adverse Events
Volunteer 004 presented at the 7-week review with symptoms of swelling of her cheeks and some mild ulceration/soreness. They were examined by the P.I. Prof Chapple, who diagnosed Erythema Multiforme, a rare reaction to either a drug the patient had been taking or to a previous herpes infection. The condition is non-infective and a delayed hypersensitivity. The P.I. deemed that it was likely to be due to a constituent of the toothpaste. The paste was withdrawn and upon review all signs and symptoms had resolved. This was not a serious adverse event, and not definitely product related, but likely to be.
Volunteer 032 was issued with toothpaste product code A90 and on Friday 21st June they reported that they had discontinued using the toothpaste (after 14 days) and requested to withdraw from the trial. They stopped using the paste due to feeling sick first thing in the morning and described an awful taste in the mouth following evening brushing. On two occasions subject 032 reported being physically sick, but did not experience these symptoms during the day. The symptoms stopped immediately on cessation of toothpaste use
REC name
London - Surrey Borders Research Ethics Committee
REC reference
13/LO/0405
Date of REC Opinion
27 Mar 2013
REC opinion
Further Information Favourable Opinion