This will be a single-blind, single-center, 3-way crossover, randomized controlled clinical trial with 3 treatment periods utilizing 32 subjects. (Fig 1, in protocol) Each treatment period will be 4 days (96 hours +/-3 hours) in accordance with the plaque accumulation model using one of the following treatment groups: an active compound MIIP-E2 gum (experimental regimen), an inactive compound gum (negative control regimen), and a no-gum (control regimen).
treatment periods utilizing 32 subjects. (Fig 1, in protocol) Each treatment period will be 4 days (96 hours +/-3 hours) in accordance with the plaque accumulation model using one of the following treatment groups: an active compound MIIP-E2 gum (experimental regimen), an inactive compound gum (negative control regimen), and a no-gum (control regimen). Each subject will be assigned to one of the following three treatment regimen sequences: 1. Control regimen followed by experimental regimen, followed by a negative control regimen, or 2. Experimental regimen followed by negative control regimen, followed by control regimen or 3. Negative control regimen followed by control regimen, followed by an experimental regimen Subjects will be asked to refrain from oral hygiene (OH) procedures and chewing gum 12 hours (+/- 2 hours) and from eating or drinking (except for water) 2 hours prior to the screening visit. During the 4-day study treatment periods, subjects will also be asked to refrain from oral hygiene practices or any elective dental treatment. Subjects can resume their regular oral hygiene procedures during the wash-out periods of approximately 10 days. At the screening, potential subjects will be given the IRB (Institutional Review Board)-approved informed consent form to read and ask questions. Also, adequate time to decide about their participation will be provided. A study representative trained and delegated by the Principal Investigator will review the IRB-approved consent and answer any questions the potential subject might have before the subject signs/dates the consent. After the subject signs and dates the consent, the study representative will sign and date the consent to confirm that the consent process was completed before initiating any study procedures. The subject will be given a copy of the signed/dated consent. A designated staff member will collect the medical and concomitant medication information for the study dentist's review. The dentist will perform an oral examination and a PLI to assess the subject's whole-mouth plaque accumulation. A score of 2 or greater will be needed to comply with the study inclusion criteria based on the Turesky modification of the Quigley and Hein Plaque Index (PLI). Other dental characteristics specified on the inclusion/ exclusion criteria will be assessed to determine study eligibility. Eligible subjects will receive a dental prophylaxis and be scheduled for a baseline appointment. During the baseline appointment, the subjects' continuance criteria and OST (oral specimen test) examination will be assessed, and an unstimulated saliva sample will be collected. Subjects' teeth will be polished, flossed, and subsequently stained to evaluate total plaque removal and an oral assessment will be performed to confirm the complete removal of plaque. If any plaque is found, the plaque will be removed by either flossing, repolishing the surface, or with an instrument. The dental examiner will assess PLI. Intraoral photos will be taken, including one front and two lateral images (right and left side). 32 subjects will be enrolled and randomly assigned to one of the treatment regimens. Subjects assigned to experimental and negative treatment regimens will perform the first product use under supervision. Each subject will be instructed to refrain from using any oral dental hygiene procedures during the study treatment period (4 days). Subjects assigned to the experimental and negative treatment regimen will use only the provided gum product three times a day for 10 minutes after meals (breakfast, lunch, and dinner). Starting on one side of the mouth, chewing for 1 minute, and switching to the other side for another minute. Afterward, they continue chewing for the remaining time however they like. To assess compliance, each subject assigned to a chewing gum product will be provided a diary to record every time they use the product and record any events associated with their study participation. Finally, subjects will be scheduled to return for an end-of-regimen visit. The last product-use treatment will be after dinner the day before the visit. Subjects will refrain from eating or drinking (except water) for two hours before their appointment. They will also be asked to rinse their mouths with water approximately 30 minutes before their visit. During the end of the treatment visit, subjects' continuance criteria will be assessed; the diary will be reviewed for compliance; an OST exam will be performed; and an unstimulated saliva sample will be collected. Subjects will rinse with a disclosing solution to reveal the accumulation of dental plaque. Intraoral photos, including one front and two lateral images (right and left sides), will be taken. Afterward, the examiner will assess the PLI, and subjects will be taken to a brushing station to brush their teeth using a provided toothbrush, fluoride-containing toothpaste, and dental floss. They will be scheduled for the next visit after a washout period of approximately 10 days. For treatments 2 and 3, the procedures mentioned in the baseline visit will be repeated (except for randomization). A new product (or no product) will be given according to the randomization assignment. The end of the treatment visit will be repeated on the fourth day of each treatment period. Lactea Therapeutics has formulated a gum product containing an active innate immune protein, MIIP-E2. This product is an ultrapure (\>99%) fully native and completely active form of bovine lactoferrin extracted and purified directly from raw milk. MIIP-E2 aims to develop a field-deployable dental care solution to enhance on-the-go oral care targeting military use. Due to the capability of the MIIP-E2 gum to coat the inner surfaces of the mouth, it can function as a barrier to biofilm adherence. The dosage of MIIP-E2 proposed for use in this study is dramatically below these acceptable levels in milk-based infant formulas, which range between 101.3 and 60.1 mg daily.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
SINGLE
Enrollment
32
Each subject will be instructed to refrain from using any oral dental hygiene procedures during the study treatment period (4 days). Subjects assigned to the experimental and negative treatment regimen will use only the provided gum product three times a day for 10 minutes after meals (breakfast, lunch, and dinner). Starting on one side of the mouth, chewing for 1 minute, and switching to the other side for another minute. Afterward, they continue chewing for the remaining time however they like. To assess compliance, each subject assigned to a chewing gum product will be provided a diary to record every time they use the product and record any events associated with their study participation. Finally, subjects will be scheduled to return for an end-of-regimen visit. MIIP-E2 is an ultrapure (\>99%) fully native and completely active form of bovine lactoferrin purified directly from raw milk.
Each subject will be instructed to refrain from using any oral dental hygiene procedures during the study treatment period (4 days). Subjects assigned to the experimental and negative treatment regimen will use only the provided gum product three times a day for 10 minutes after meals (breakfast, lunch, and dinner). Starting on one side of the mouth, chewing for 1 minute, and switching to the other side for another minute. Afterward, they continue chewing for the remaining time however they like. To assess compliance, each subject assigned to a chewing gum product will be provided a diary to record every time they use the product and record any events associated with their study participation. Finally, subjects will be scheduled to return for an end-of-regimen visit.
Oral Health Research Institute
Indianapolis, Indiana, United States
RECRUITINGdental plaque
Dental plaque was identified using a disclosing solution and scored using the Turesky modification of the Quigley-Hein Plaque Index (PLI). The index score was scored between 0 and 5, with 0 = no plaque detected and 5= = Plaque covering 2/3 or more of the tooth's crown. The remaining values are based on the amount of plaque covering the tooth. The higher the score, the more plaque accumulated and the worse the outcome for the surface. Each tooth, except the third molars, will be scored at six sites: Mesio-Buccal, buccal, disto-buccal, mesio-lingual, lingual, and disto-lingual. The plaque score index for an individual is determined by adding all the individual scores and dividing the total score by the number of surfaces examined. A score would range from 0.1 to 3.0 (0.1-1.0= = mild inflammation; 1.1-2.0= = moderate inflammation; and 2.1-3.0= = severe inflammation).
Time frame: At the end of 4 days of intervention.
16S sequencing
In addition, patient saliva samples will be taken before and after each treatment regimen for 16S rRNA (ribosomal ribonucleic acid) microbiome sequencing using the Qiagen PAXgene Saliva Collector and protocols that accompany the collection kit (https://www.qiagen.com /us/products/discovery-and-translational-research/sample-collection-stabilization/dna/pax gene-saliva-collector). Sequencing will be performed at CD Genomics (a third-party vendor) using protocols for full-length PacBio (Pacific Biosciences) sequencing and IRB#: 25945 Version Date: February 3, 2025 Page 6 of 18 analyzed using standard methodologies to identify microbial taxonomy. No human genetic information will be collected or analyzed using this methodology.
Time frame: At the end of 4 days of intervention.
Dental Plaque Visual Assessment with photographs
Images of dental plaque will be used for both qualitative representations of outcomes in future reports as well as used as a secondary, complementary quantitative analysis for the PLI assessment. For the quantitative analysis, plaque coverage on teeth will be assessed using an image thresholding area measurement as previously described. This analysis is anticipated to provide similar results to the PLI as mentioned earlier but may allow for further analysis and quantitative precision. Depending on preliminary analysis, these measurements may be used to further assess details of product efficacy, such as regional changes in plaque across teeth, to understand whether the reduction in plaque occurred primarily on surfaces with direct exposure to the gum or throughout the mouth.
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Time frame: At the end of 4 days of intervention.