MicroRNA and MicroRNA Inhibitors Socket Study, Pilot Clinical Trial

NCT ID: NCT02579187

Last Updated: 2019-07-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-31

Study Completion Date

2030-09-30

Brief Summary

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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

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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

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Tooth Extraction Status Nos

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

HEALTH_SERVICES_RESEARCH

Blinding Strategy

SINGLE

Participants

Study Groups

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control group

CBCT scan limited to the dental arch that includes the study site will be obtained. All subjects will receive local infiltrative anesthesia, following which minimally invasive tooth extraction will be performed. After tooth extraction clinical measurements of the site will also be obtained and recorded for both groups (i.e. keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness). A biodegradable sponge (type I bovine collagen) to stabilize the blood clot will be placed.The site will be stabilized with a simple external, cross mattress suture. Blood , wound fluid, and saliva samples will be taken periodicallly. In addition, photos/videos, periapical xrays and PVS impressions will be obtained.

Group Type PLACEBO_COMPARATOR

tooth extraction

Intervention Type PROCEDURE

The study tooth will be removed

CBCT scan

Intervention Type RADIATION

a CBCT scan limited to the dental arch that includes the study side will be obtained

Anesthesia

Intervention Type DRUG

all subjects will receive local infiltrative anesthesia, prior to extraction of the tooth

clinical measurements

Intervention Type OTHER

After tooth extraction, clinical measurements of the site will be obtained and recorded (keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness

Biodegradable sponge (type I bovine collagen)

Intervention Type DRUG

control group subjects will receive a biodegradable sponge (type I bovine collagen) to stabilize the clot

cross mattress suture

Intervention Type PROCEDURE

The site will be stabilized with a simplet external, cross mattress suture

Blood

Intervention Type PROCEDURE

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)

Photos/videos

Intervention Type OTHER

subjects will have photos and/or videos of the extraction site and/or implant taken at each visit.

Wound fluid

Intervention Type PROCEDURE

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

Intervention Type PROCEDURE

approximately 2 mls of saliva will be obtained in a minimally invasive manner at the time of extraction and at 14 weeks post extraction.

periapical xray

Intervention Type RADIATION

periapical xrays will be obtained at screening, 16 weeks and at 12 month followup time point

PVS impression

Intervention Type OTHER

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.

Experimental group 1

CBCT scan limited to the dental arch that includes the study site will be obtained. All subjects will receive local infiltrative anesthesia, following which minimally invasive tooth extraction will be performed. After tooth extraction clinical measurements of the site will also be obtained and recorded for both groups (i.e. keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness). 10µg of pSil-miR200c plasmids in a biodegradable sponge (type I bovine collagen) will be locally delivered. The site will be stabilized with a simple external, cross mattress suture. Blood, wound fluid, and saliva samples will be taken periodicallly. In addition, photos/videos, periapical xrays and PVS impressions will be obtained.

Group Type ACTIVE_COMPARATOR

tooth extraction

Intervention Type PROCEDURE

The study tooth will be removed

CBCT scan

Intervention Type RADIATION

a CBCT scan limited to the dental arch that includes the study side will be obtained

Anesthesia

Intervention Type DRUG

all subjects will receive local infiltrative anesthesia, prior to extraction of the tooth

clinical measurements

Intervention Type OTHER

After tooth extraction, clinical measurements of the site will be obtained and recorded (keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness

10µg of pSil-miR200c

Intervention Type DRUG

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

cross mattress suture

Intervention Type PROCEDURE

The site will be stabilized with a simplet external, cross mattress suture

Blood

Intervention Type PROCEDURE

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)

Photos/videos

Intervention Type OTHER

subjects will have photos and/or videos of the extraction site and/or implant taken at each visit.

Wound fluid

Intervention Type PROCEDURE

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

Intervention Type PROCEDURE

approximately 2 mls of saliva will be obtained in a minimally invasive manner at the time of extraction and at 14 weeks post extraction.

periapical xray

Intervention Type RADIATION

periapical xrays will be obtained at screening, 16 weeks and at 12 month followup time point

PVS impression

Intervention Type OTHER

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.

Experimental group 2

CBCT scan limited to the dental arch that includes the study site will be obtained. All subjects will receive local infiltrative anesthesia, following which minimally invasive tooth extraction will be performed. After tooth extraction clinical measurements of the site will also be obtained and recorded for both groups (i.e. keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness). 10µg of PMIS miR200a plasmids in a biodegradable sponge (type I bovine collagen) will be locally delivered. The site will be stabilized with a simple external, cross mattress suture. Blood, wound fluid, and saliva samples will be taken periodicallly. In addition, photos/videos, periapical xrays and PVS impressions will be obtained.

Group Type ACTIVE_COMPARATOR

tooth extraction

Intervention Type PROCEDURE

The study tooth will be removed

CBCT scan

Intervention Type RADIATION

a CBCT scan limited to the dental arch that includes the study side will be obtained

Anesthesia

Intervention Type DRUG

all subjects will receive local infiltrative anesthesia, prior to extraction of the tooth

clinical measurements

Intervention Type OTHER

After tooth extraction, clinical measurements of the site will be obtained and recorded (keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness

cross mattress suture

Intervention Type PROCEDURE

The site will be stabilized with a simplet external, cross mattress suture

10µg of PMIS miR200a plasmids

Intervention Type DRUG

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

Blood

Intervention Type PROCEDURE

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)

Photos/videos

Intervention Type OTHER

subjects will have photos and/or videos of the extraction site and/or implant taken at each visit.

Wound fluid

Intervention Type PROCEDURE

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

Intervention Type PROCEDURE

approximately 2 mls of saliva will be obtained in a minimally invasive manner at the time of extraction and at 14 weeks post extraction.

periapical xray

Intervention Type RADIATION

periapical xrays will be obtained at screening, 16 weeks and at 12 month followup time point

PVS impression

Intervention Type OTHER

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.

Experimental group 3

CBCT scan limited to the dental arch that includes the study site will be obtained. All subjects will receive local infiltrative anesthesia, following which minimally invasive tooth extraction will be performed. After tooth extraction clinical measurements of the site will also be obtained and recorded for both groups (i.e. keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness). 5µg of pSil-miR200c and 5µg of PMIS miR200a plasmids in a biodegradable sponge (type I bovine collagen) will be locally delivered. The site will be stabilized with a simple external, cross mattress suture. Blood, wound fluid, and saliva samples will be taken periodicallly. In addition, photos/videos, periapical xrays and PVS impressions will be obtained.

Group Type ACTIVE_COMPARATOR

tooth extraction

Intervention Type PROCEDURE

The study tooth will be removed

CBCT scan

Intervention Type RADIATION

a CBCT scan limited to the dental arch that includes the study side will be obtained

Anesthesia

Intervention Type DRUG

all subjects will receive local infiltrative anesthesia, prior to extraction of the tooth

clinical measurements

Intervention Type OTHER

After tooth extraction, clinical measurements of the site will be obtained and recorded (keratinized mucosa width, horizontal ridge width, facial and lingual bone thickness

cross mattress suture

Intervention Type PROCEDURE

The site will be stabilized with a simplet external, cross mattress suture

5µg of pSil-miR200c and 5µg of PMIS miR200a

Intervention Type DRUG

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

Blood

Intervention Type PROCEDURE

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)

Photos/videos

Intervention Type OTHER

subjects will have photos and/or videos of the extraction site and/or implant taken at each visit.

Wound fluid

Intervention Type PROCEDURE

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

Intervention Type PROCEDURE

approximately 2 mls of saliva will be obtained in a minimally invasive manner at the time of extraction and at 14 weeks post extraction.

periapical xray

Intervention Type RADIATION

periapical xrays will be obtained at screening, 16 weeks and at 12 month followup time point

PVS impression

Intervention Type OTHER

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.

Interventions

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tooth extraction

The study tooth will be removed

Intervention Type PROCEDURE

CBCT scan

a CBCT scan limited to the dental arch that includes the study side will be obtained

Intervention Type RADIATION

Anesthesia

all subjects will receive local infiltrative anesthesia, prior to extraction of the tooth

Intervention Type DRUG

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

Intervention Type OTHER

Biodegradable sponge (type I bovine collagen)

control group subjects will receive a biodegradable sponge (type I bovine collagen) to stabilize the clot

Intervention Type 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

Intervention Type DRUG

cross mattress suture

The site will be stabilized with a simplet external, cross mattress suture

Intervention Type PROCEDURE

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

Intervention Type 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

Intervention Type DRUG

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)

Intervention Type PROCEDURE

Photos/videos

subjects will have photos and/or videos of the extraction site and/or implant taken at each visit.

Intervention Type OTHER

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

Intervention Type 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.

Intervention Type PROCEDURE

periapical xray

periapical xrays will be obtained at screening, 16 weeks and at 12 month followup time point

Intervention Type RADIATION

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.

Intervention Type OTHER

Other Intervention Names

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local infiltrative anesthesia Bovine collagen pSil-miR-200C plasmids PMIS miR200a plasmids 5µg of pSil-miR200c and 5µg of PMIS miR200a plasmids venipuncture

Eligibility Criteria

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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).
Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Gustavo Avila-Ortiz DDS, MS, PhD

OTHER

Sponsor Role lead

Responsible Party

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Gustavo Avila-Ortiz DDS, MS, PhD

DDS

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Brad Amendt, MS

Role: STUDY_DIRECTOR

UIowa College of Dentistry

Locations

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UIowa

Iowa City, Iowa, United States

Site Status

Countries

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United States

Other Identifiers

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201607780

Identifier Type: -

Identifier Source: org_study_id

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