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

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

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

Study Overview

• Status: Completed
• Conditions: Gingivitis
• Intervention / Treatment: Drug: 0.3X ACCS; Drug: 1X ACCS (Amnion-derived Cellular Cytokine Solution); Drug: Normal saline

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 54
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02142
      • Forsyth Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose 0.3X ACCS; 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; 0.3X ACCS will be applied to the gingival margin daily 5 days per week for 2 weeks; Other Names: Diluted ACCS
Experimental: High dose 1X ACCS; 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); 1X ACCS will be applied to the gingival margin daily 5 days per week for 2 weeks; Other Names: ACCS
Placebo Comparator: Normal saline; 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; Saline will be applied to the gingival margin daily 5 days per week for 2 weeks; Other Names: saline placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Noveome Biotherapeutics, formerly Stemnion
• Investigators: Study Director: David L Steed, MD, Noveome Biotherapeutics, formerly Stemnion

Study record dates

Study Major Dates

• Study Start: March 1, 2014
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 24, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): November 29, 2016
• Last Update Submitted That Met QC Criteria: November 28, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Periodontitis; Gingivitis; ACCS
• Additional Relevant MeSH Terms: Infections; Stomatognathic Diseases; Periodontal Diseases; Mouth Diseases; Gingival Diseases; Gingivitis
• Other Study ID Numbers: ST-04-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO