MicroRNA and MicroRNA Inhibitors Socket Study, Pilot Clinical Trial

Tooth Extraction Status Nos Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02579187
• Other study ID #: 201607780
• Status: Withdrawn
• Phase: Phase 1
• Start date: December 31, 2025
• Est. completion date: September 2030

Study information

• Verified date: July 2019
• Source: University of Iowa
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 2030
• Est. primary completion date: September 2030
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 25 Years to 65 Years

Eligibility

INCLUSION CRITERIA

• Age: 25 to 65 years.

• Gender: No restriction.

• Subjects must require a single-rooted tooth extraction (Tooth deemed as periodontally, endodontically and/or restoratively hopeless).

• Subjects must be able and willing to follow instructions related to the study procedures.

• Subjects must have read, understood and signed an informed consent form.

EXCLUSION CRITERIA

• Reported allergy or hypersensitivity to any of the products to be used in the study.

• Severe hematologic disorders, such as leukemia.

• Active severe infectious diseases that may compromise normal healing.

• Liver or kidney dysfunction/failure.

• Currently under cancer treatment or history of cancer of any kind.

• Subjects who have a long-term history of oral bisphosphonate use (i.e. 4 years or more).

• Subjects with a history of IV bisphosphonates.

• Subjects with uncontrolled diabetes.

• Subjects with severe metabolic bone diseases, such as Paget's disease of bone, will be excluded.

• Pregnant women or nursing mothers.

• Smokers: Within 6 months of study onset.

• Concomitant medications: Subjects on concomitant drug therapy for systemic conditions, such as antibiotics or patient taking non-steroidal anti-inflammatory (NSAID) agents that may affect the outcomes of the study will not be included in the study. Subjects taking biologics or disease modifying agents will also be excluded. Occasional, short-term use (7-14 days) of analgesics or common cold medications is permitted.

• Any other non-specified reason that from the point of views of the investigators will make a candidate not a suitable subject for the study (e.g. limited mouth opening).

Related Conditions & MeSH terms

• Tooth Extraction Status Nos

Intervention

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
• 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
• 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
• 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.

Locations

Country	Name	City	State
United States	UIowa	Iowa City	Iowa

Sponsors (1)

Lead Sponsor	Collaborator
Gustavo Avila-Ortiz DDS, MS, PhD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of mineralized tissue upon histomorphometric analysis of bone core biopsies	compared using exact Wilcoxon rank sum tests	at 16 weeks postoperatively
Secondary	Bucco-lingual width changes of the alveolar ridge (in mm)	Fisher's exact tests will be used to compare the treatment groups	up to 16 weeks postoperatively
Secondary	Mid-buccal height changes of the alveolar ridge (in mm)	compared using exact Wilcoxon rank sum tests	up to 16 weeks postoperatively
Secondary	Mid-lingual height changes of the alveolar ridge (in mm)	compared using exact Wilcoxon rank sum tests	up to 16 weeks postoperatively
Secondary	Volumetric reduction of the alveolar ridge (in cc) via CBCT scan analyses	compared using exact Wilcoxon rank sum tests	at 16 weeks postoperatively
Secondary	Expression of different biomarkers (VEGF, PDGF, TGF-b, IL-1b, TNF-a) in wound fluid expressed in pg/ml	compared using exact Wilcoxon rank sum tests	up to 4 weeks postoperatively