NCT02579187

MicroRNA and MicroRNA Inhibitors Socket Study, Pilot Clinical Trial

Efficacy of Local Delivery of MicroRNAs and MicroRNA Inhibitors in Promoting Osteogenesis and Modulating Local Inflammation: A Pilot Clinical Trial Using the Tooth Socket Model

• Status: Withdrawn
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 0 (actual)
• Sponsor: Gustavo Avila-Ortiz DDS, MS, PhD · Academic / Other
• Sex: All
• Age: 25 Years – 65 Years
• Healthy volunteers: Accepted

Summary

To evaluate the efficacy of locally delivering plasmid DNAs encoding microRNAs, and/or microRNA inhibitors, in the promotion of osteogenesis and modulation of the inflammatory response on the basis of different clinical, radiographic, histologic and biomolecular outcomes in post-extraction socket defects in humans.

Detailed description

The purpose of this study is to evaluate the efficacy of locally delivering plasmid DNAs encoding microRNAS and/or microRNA inhibitors, a naturally occurring microRNA molecule, in the promotion of bone formation and attenuation of local inflammation in a tooth socket model in humans. Patients requiring tooth extractions and future tooth replacement therapy with a dental implant will be eligible for the study. Recruited subjects will be randomly assigned to either a control (tooth extraction and 10µg empty vector in bovine collagen sponge) or one of 3 experimental groups: * Experimental group 1: Tooth extraction and bovine collagen sponge containing 10µg of pSil-miR200c * Experimental Group 2: Tooth extraction and bovine Collagen sponge containing 10µg of PMIS miR200a * Experimental Group 3: Tooth extraction and bovine Collagen sponge containing 5µg of pSil-miR200c and 5µg of PMIS miR200a Subjects will be clinically re-evaluated at 1, 2, 3 and 4 weeks. In each one of these visits, a fluid sample will be obtained from the healing site in a minimally invasive manner to assess local biomolecular profiles. Blood samples will be drawn at 1, 2, 3, 4 and 14 week visits to assess for miR-200c and PMIS-miR 200a expression and liver function. Photos and/or videos will also be obtained. A CBCT scan and a saliva sample (approx. 2 ml) will also be obtained at baseline and at 14 weeks to assess bone volume and intraoral biomolecular profiles, respectively. Implant placement surgery will be performed at 16 weeks from the time of tooth extraction. A bone core biopsy will be harvested at this time for histologic analysis. A periapical radiograph (small dental x-ray image) will be obtained at baseline (before tooth extraction) and at 14 weeks (prior to implant placement) to assess bone height changes. Follow-up visits will occur at 6 months and 12 months post implant at which time measurements and photos will be taken.

Conditions

• Tooth Extraction Status Nos

Interventions

Type	Name	Description
PROCEDURE	tooth extraction	The study tooth will be removed
RADIATION	CBCT scan	a CBCT scan limited to the dental arch that includes the study side will be obtained
DRUG	Anesthesia	all subjects will receive local infiltrative anesthesia, prior to extraction of the tooth
OTHER	clinical measurements	After tooth extraction, clinical measurements of the site will be obtained and recorded (keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness
DRUG	Biodegradable sponge (type I bovine collagen)	control group subjects will receive a biodegradable sponge (type I bovine collagen) to stabilize the clot
DRUG	10µg of pSil-miR200c	subjects in the experimental group will receive a 10µg of pSil-miR200c plasmids in a biodegradable sponge (type I bovine collagen) to stabilize the clot
PROCEDURE	cross mattress suture	The site will be stabilized with a simplet external, cross mattress suture
DRUG	10µg of PMIS miR200a plasmids	subjects in the experimental group will receive a 10µg of PMIS miR200a plasmids in a biodegradable sponge (type I bovine collagen) to stabilize the clot
DRUG	5µg of pSil-miR200c and 5µg of PMIS miR200a	subjects in the experimental group will receive a 5µg of pSil-miR200c and 5µg of PMIS miR200a plasmids in a biodegradable sponge (type I bovine collagen) to stabilize the clot
PROCEDURE	Blood	Subjects will have venipuncture performed to obtain a small blood sample (approx. 2 ml) to assess for miR-200c and PMIS-miR-200a expression and liver function (AST, ALT, bilirubin levels)
OTHER	Photos/videos	subjects will have photos and/or videos of the extraction site and/or implant taken at each visit.
PROCEDURE	Wound fluid	a small sample of wound fluid will be obtained from the extraction site in a minimally invasive manner using a paper point at 1, 2, 3 \& 4 weeks post extraction
PROCEDURE	saliva	approximately 2 mls of saliva will be obtained in a minimally invasive manner at the time of extraction and at 14 weeks post extraction.
RADIATION	periapical xray	periapical xrays will be obtained at screening, 16 weeks and at 12 month followup time point
OTHER	PVS impression	PVS impressions will be taken to plan the implant placement surgery. This will be done at the screening visit and also at 14 weeks post extraction.

Timeline

• Start date: 2025-12-31
• Primary completion: 2030-09-01
• Completion: 2030-09-01
• First posted: 2015-10-19
• Last updated: 2019-07-17

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study