MicroRNA and MicroRNA Inhibitors Socket Study, Pilot Clinical Trial

Gustavo Avila-Ortiz DDS, MS, PhD

Status and phase

Withdrawn

Phase 1

Conditions

Tooth Extraction Status Nos

Treatments

Procedure: cross mattress suture

Drug: 10µg of pSil-miR200c

Other: PVS impression

Other: Photos/videos

Procedure: tooth extraction

Other: clinical measurements

Radiation: periapical xray

Procedure: saliva

Drug: Biodegradable sponge (type I bovine collagen)

Drug: 10µg of PMIS miR200a plasmids

Procedure: Wound fluid

Procedure: Blood

Radiation: CBCT scan

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

Drug: Anesthesia

Study type

Interventional

Funder types

Other

Identifiers

NCT02579187

201607780

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

25 to 65 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

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).

Trial design

Primary purpose

Health Services Research

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Single Blind

0 participants in 4 patient groups, including a placebo group

control group

Placebo Comparator group

Description:

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.

Treatment:

Drug: Anesthesia

Radiation: CBCT scan

Procedure: Blood

Drug: Biodegradable sponge (type I bovine collagen)

Procedure: cross mattress suture

Procedure: tooth extraction

Radiation: periapical xray

Other: clinical measurements

Other: PVS impression

Other: Photos/videos

Procedure: saliva

Procedure: Wound fluid

Experimental group 1

Active Comparator group

Description:

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.

Treatment:

Drug: Anesthesia

Radiation: CBCT scan

Procedure: Blood

Procedure: cross mattress suture

Procedure: tooth extraction

Radiation: periapical xray

Other: clinical measurements

Other: PVS impression

Other: Photos/videos

Drug: 10µg of pSil-miR200c

Procedure: saliva

Procedure: Wound fluid

Experimental group 2

Active Comparator group

Description:

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.

Treatment:

Drug: Anesthesia

Radiation: CBCT scan

Procedure: Blood

Drug: 10µg of PMIS miR200a plasmids

Procedure: cross mattress suture

Procedure: tooth extraction

Radiation: periapical xray

Other: clinical measurements

Other: PVS impression

Other: Photos/videos

Procedure: saliva

Procedure: Wound fluid

Experimental group 3

Active Comparator group

Description:

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.

Treatment:

Drug: Anesthesia

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

Radiation: CBCT scan

Procedure: Blood

Procedure: cross mattress suture

Procedure: tooth extraction

Radiation: periapical xray

Other: clinical measurements

Other: PVS impression

Other: Photos/videos

Procedure: saliva