Clinical trial NCT02579187: MicroRNA and MicroRNA Inhibitors Socket Study, Pilot 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Tooth Extraction Status Nos
Lead sponsor: University of Iowa
Sponsor class: OTHER
First posted: 2015-10-19
Enrollment: 0
Sex: ALL
Minimum age (years): 25
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief 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.

Eligibility 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).

Primary outcomes:
measure: Percent of mineralized tissue upon histomorphometric analysis of bone core biopsies
timeFrame: at 16 weeks postoperatively
Secondary outcomes:
measure: Bucco-lingual width changes of the alveolar ridge (in mm)
timeFrame: up to 16 weeks postoperatively
measure: Mid-buccal height changes of the alveolar ridge (in mm)
timeFrame: up to 16 weeks postoperatively
measure: Mid-lingual height changes of the alveolar ridge (in mm)
timeFrame: up to 16 weeks postoperatively
measure: Volumetric reduction of the alveolar ridge (in cc) via CBCT scan analyses
timeFrame: at 16 weeks postoperatively
measure: Expression of different biomarkers (VEGF, PDGF, TGF-b, IL-1b, TNF-a) in wound fluid expressed in pg/ml
timeFrame: up to 4 weeks postoperatively
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: UIowa
state: Iowa
Study officials:
affiliation: UIowa College of Dentistry
name: Brad Amendt, MS
role: STUDY_DIRECTOR
References: