Treatment of Human Gingivitis With Amnion-derived Cellular Cytokine Solution (ACCS)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of oral topical application of Amnion-derived Cellular Cytokine Solution (ACCS) in subjects with gingivitis

Detailed Description
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This randomized blinded study will evaluate the use of ACCS in subjects with gingivitis. Two doses of ACCS will be used. It will be given topically intra-orally daily Monday through Friday for 2 weeks. In the first cohort, a low dose of ACCS or saline will be given by random chance. If there are no safety issues, cohort two will include a higher dose of ACCS randomized with saline. Pocket depth, plaque index, gingival index, and bleeding on probing will be assessed. To assess shifts in supragingival flora, a qualitative and quantitative microbial analysis will be performed for common oral bacteria. There will also be an analysis of inflammatory cytokines in crevicular fluid at the beginning and end of the study. Comparisons of adverse events and outcomes will be made between the subjects receiving low dose ACCS, high dose ACCS, and saline.

Official Title
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Treatment of Human Gingivitis With Topical ACCS: a Two Week Safety Dose-ranging and Proof-of-principle Trial

Conditions
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Gingivitis

Intervention / Treatment
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* Drug: 1X ACCS (Amnion-derived Cellular Cytokine Solution)
* Drug: Normal saline
* Drug: 0.3X ACCS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: good general health ages 18-70 years minimum of 20 natural teeth modified gingival index score of 2.0 or greater and >40 percent bleeding sites at initial presentation. Exclusion Criteria: presence of orthodontic appliance soft or hard tissue tumor of the oral cavity carious lesion requiring immediate treatment participation in another clinical trial within 30 days pregnant or breast-feeding women women of child-bearing potential refusing to use an acceptable method of birth control antibiotic therapy within the last 30 days chronic use (> 3 times/week) of non-steroidal anti-inflammatory medications (NSAID). Any use of steroids. Low dose (<325 mg) aspirin is allowed. immune-compromised subjects subjects with liver or kidney dysfunction on blood tests as evidenced by a value equal to or greater than 2X the upper limit of normal. any medical history or any concomitant medication that might affect the assessment of the study treatment or periodontal tissues such as diabetes rheumatoid arthritis, Crohn's disease, use of nifedipine, phenytoin (Dilantin), anticoagulant medications (e.g. warfarin), ongoing cancer treatment either with radiation of chemotherapy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose 0.3X ACCS<br>20 microliters of 0.3X ACCS per tooth is applied directly excluding third molars by dental professional daily Monday through Friday for two weeks | Drug: 0.3X ACCS<br>* 0.3X ACCS will be applied to the gingival margin daily 5 days per week for 2 weeks<br>* Other names: Diluted ACCS;|
| Experimental: High dose 1X ACCS<br>20 microliters of 1X ACCS per tooth is applied directly excluding third molars by dental professional daily Monday through Friday for two weeks | Drug: 1X ACCS (Amnion-derived Cellular Cytokine Solution)<br>* 1X ACCS will be applied to the gingival margin daily 5 days per week for 2 weeks<br>* Other names: ACCS;|
| Placebo Comparator: Normal saline<br>20 microliters of saline placebo per tooth is applied directly excluding third molars by dental professional daily Monday through Friday for two weeks | Drug: Normal saline<br>* Saline will be applied to the gingival margin daily 5 days per week for 2 weeks<br>* Other names: saline placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse/serious adverse events |  | End of two weeks of treatment and at two weeks follow-up visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Probing pocket depth | Depth will be measured at six sites per tooth | Bseline and after two weeks of treatment | 
| Modified gingival index | Gingival index will be measured at six sites per tooth | Baseline and after two weeks of treatment | 
| Bleeding on probing | Bleeding will be measured at six sites per tooth | Baseline and after two weeks of treatment | 
| Plaque index | Only the gingival third of the tooth will be evaluated | Baseline and after two weeks of treatment | 
| Microbial analysis | 6 teeth will be sampled | Baseline and after two weeks of treatment | 
| Cytokine analysis | Inflammatory cytokines will be sampled in crevicular fluid | Baseline and after two weeks of therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gingivitis, Periodontitis, ACCS