Evaluation of Anti-biofilm Effects of Ferumoxytol (Feraheme) Using an in Situ Biofilm Demineralization Model

NCT03678012 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: 1802077294
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 2

Brief Summary

To evaluate the effects of a clinically approved and commercially available iron oxide formulation Ferumoxytol (Feraheme®) to control cariogenic biofilms and enamel demineralization. This study will be testing topical application of Ferumoxytol extra-orally using a standard in situ biofilm demineralization model.

Conditions

Dental Caries

Outcome Measures

Primary Outcomes (2)

• Biofilm Analyses-cell viability

  The effect of the treatments will be analyzed in terms of biochemical and microbiological composition of the biofilm formed. Colony forming unit (CFU) will be used to quantify the number of viable cells in biofilms.

  14 days

• Biofilm Analysis-extracellular polysaccharides

  Biofilm EPS amount (weight in milligram) will be determined using colorimetric assay.

  14 days

Secondary Outcomes (1)

• Assessment of Enamel Demineralization by Means of Surface Microhardness Test (SMH)

  14 days

Study Arms (3)

Ferumoxytol/Hydrogen peroxide

ACTIVE COMPARATOR

1.5% Ferumoxytol / 3% Hydrogen Peroxide (H2O2) 1:1 ratio

Drug: Ferumoxytol/Hydrogen peroxide

Hydrogen peroxide

PLACEBO COMPARATOR

Sham Solution / 3% Hydrogen Peroxide (H2O2) 1:1 ratio

Drug: Hydrogen Peroxide

Water

SHAM COMPARATOR

Sham solution (water; negative control)

Drug: Water

Interventions

Ferumoxytol/Hydrogen peroxide DRUG

1.5% Ferumoxytol / 3% Hydrogen Peroxide (H2O2) 1:1 ratio. Each subject will use this product during one of three treatment periods in the crossover study design.

Also known as: Feraheme

Ferumoxytol/Hydrogen peroxide

Hydrogen Peroxide DRUG

Sham Solution / 3% Hydrogen Peroxide (H2O2) 1:1 ratio. Each subject will use this product during one of three treatment periods in the crossover study design.

Hydrogen peroxide

Water DRUG

Sham solution (water; negative control). Each subject will use this product during one of three treatment periods in the crossover study design.

Water

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females 18 to 85 years of age and in good general and oral health without any known allergies to commercial dental products;
• Evidence of a personally signed and dated informed consent document indicating the subject has been informed of all pertinent aspects of the trial;
• Willingness to use the assigned products according to instructions, availability for appointments and likelihood of completing the clinical trial;
• Willing to adhere to the study requirements and restrictions;
• Lower partial denture wearers who have a lower partial denture made for them as a part of a partial denture panel under study 14-I-098 (IRB # 1407637739) or who agree to wear their own pre-approved lower partial denture that can house both specimens on one side of their partial denture.

You may not qualify if:

• Normal salivary flow rate (stimulated and unstimulated flow of ≥ 0.8 mL/min and ≥ 0.2 mL/min, respectively) ascertained from the Screening visit;
• Willing and capable of wearing the lower partial denture 24 hours a day for the three, two-week treatment periods. Note: for persons who would otherwise qualify but whose lower partial denture needs repair, the individual may be listed as "pending". Once the partial denture has been repaired and adjusted to fit adequately for the subject to wear the lower partial denture 24 hours a day, the subject may be considered "qualified", complete their minimum 4 to 5 days washout period (of their own fluoridated toothpaste use) and continue with visit 2 in the study;
• Absence of significant oral soft tissue pathology and dental caries, based on the dentist's visual examination and at the discretion of the investigator. Note: for persons who would otherwise qualify but who present at screening with dental caries requiring treatment, the individual may be listed as "pending". If the subject completes the restorative work within an acceptable amount of time, the subject may be considered qualified, complete their minimum 4 to 5 day washout period (of their own fluoridated toothpaste use) and continue with visit 2 in the study; and
• Adequate oral hygiene (i.e. brush teeth daily and exhibit no signs of oral neglect).
• Are taking or have ever taken bisphosphonate drugs (i.e., Fosamax, Actonel and Boniva) for the treatment of osteoporosis;
• Use of blood thinning medications that prohibit the safe conduct of a dental cleaning (\*NOTE: Subjects who are taking blood thinners in which written verification is obtained from their physician indicating their PT/INR levels (anti-coagulation blood levels) are at an acceptable level to avoid serious complications, such as bleeding during dental cleanings, may be accepted into the study);
• Suspected alcohol or substance abuse (e.g., amphetamines, benzodiazepines, cocaine, marijuana, opiates) in the past year;
• Report allergy to products (Ferumoxytol or other drugs or specific ingredients) used in the study, a reported history of multiple drug allergies or known hypersensitivity to any iron products;
• Scheduled for MRI for the head region within three months after study participation involving Ferumoxytol application;
• Have a history of significant adverse effects following the use of oral hygiene products such as dentifrices and mouth rinses;
• Use of antimicrobial agents/antibiotics whether prescribed or over-the-counter within two weeks prior to each treatment visit;
• Presence of severe marginal gingivitis or moderate/advanced periodontitis based on the clinical examination and discretion of the dental examiner;
• Subjects who during the study will receive dental treatment, which may affect their participation (i.e. oral prophylaxis). Emergency treatment will be allowed if necessary;
• Those requiring antibiotic premedication prior to dental treatment;
• Participation in a dental clinical trial involving oral care products within 30 days of randomization (Baseline Visit);

Sponsors & Collaborators

• University of Pennsylvania: lead
• Indiana University: collaborator

Study Sites (2)

Oral Health Research Institute

Indianapolis, Indiana, 46202, United States

Location

University of Pennsylvania, School of dental medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (2)

• Cormode DP, Gao L, Koo H. Emerging Biomedical Applications of Enzyme-Like Catalytic Nanomaterials. Trends Biotechnol. 2018 Jan;36(1):15-29. doi: 10.1016/j.tibtech.2017.09.006. Epub 2017 Oct 26.

  PMID: 29102240 BACKGROUND

• Gao L, Liu Y, Kim D, Li Y, Hwang G, Naha PC, Cormode DP, Koo H. Nanocatalysts promote Streptococcus mutans biofilm matrix degradation and enhance bacterial killing to suppress dental caries in vivo. Biomaterials. 2016 Sep;101:272-84. doi: 10.1016/j.biomaterials.2016.05.051. Epub 2016 Jun 2.

  PMID: 27294544 BACKGROUND

MeSH Terms

Conditions

Dental Caries

Interventions

Ferrosoferric Oxide; Hydrogen Peroxide; Water

Condition Hierarchy (Ancestors)

Tooth Demineralization; Tooth Diseases; Stomatognathic Diseases

Intervention Hierarchy (Ancestors)

Ferric Compounds; Iron Compounds; Inorganic Chemicals; Ferrous Compounds; Minerals; Peroxides; Oxides; Anions; Ions; Electrolytes; Reactive Oxygen Species; Free Radicals; Oxygen Compounds; Organic Chemicals; Hydroxides; Alkalies

Study Officials

• Hyun Koo, Ph.D

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

• Domenick Zero, Ph.D

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The study dentist, specimen/sample analysis technicians and the statistician will be blinded to the product allocation of subjects.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This will be a randomized, crossover, single blind in situ study with three test periods utilizing 16 subjects. The subjects in this study are lower partial denture wearers who have already had a study partial denture made for them as a part of a partial denture panel under 14-I-098 (IRB # 1407637739) or who will wear their own lower partial denture which was previously approved as part of the panel. The study partial dentures or personal partial dentures can house the specimen holders in two hollowed out areas of the buccal surface of two posterior denture teeth. The subjects will wear the lower partial dentures with enamel specimens in place for three consecutive 14-day study periods.

Study Record Dates

• First Submitted: September 7, 2018
• First Posted: September 19, 2018
• Study Start: June 7, 2018
• Primary Completion: August 16, 2018
• Study Completion: August 16, 2018
• Last Updated: September 19, 2018

Record last verified: 2018-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)