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MicroRNA and MicroRNA Inhibitors Socket Study, Pilot Clinical Trial

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02579187
Recruitment Status : Withdrawn (withdrawn study from IRB)
First Posted : October 19, 2015
Last Update Posted : July 17, 2019
Sponsor:
Information provided by (Responsible Party):
Gustavo Avila-Ortiz DDS, MS, PhD, University of Iowa

Tracking Information
First Submitted Date  ICMJE October 12, 2015
First Posted Date  ICMJE October 19, 2015
Last Update Posted Date July 17, 2019
Estimated Study Start Date  ICMJE December 31, 2025
Estimated Primary Completion Date September 2030   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
Percent of mineralized tissue upon histomorphometric analysis of bone core biopsies [ Time Frame: at 16 weeks postoperatively ]
compared using exact Wilcoxon rank sum tests
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
  • Bucco-lingual width changes of the alveolar ridge (in mm) [ Time Frame: up to 16 weeks postoperatively ]
    Fisher's exact tests will be used to compare the treatment groups
  • Mid-buccal height changes of the alveolar ridge (in mm) [ Time Frame: up to 16 weeks postoperatively ]
    compared using exact Wilcoxon rank sum tests
  • Mid-lingual height changes of the alveolar ridge (in mm) [ Time Frame: up to 16 weeks postoperatively ]
    compared using exact Wilcoxon rank sum tests
  • Volumetric reduction of the alveolar ridge (in cc) via CBCT scan analyses [ Time Frame: at 16 weeks postoperatively ]
    compared using exact Wilcoxon rank sum tests
  • Expression of different biomarkers (VEGF, PDGF, TGF-b, IL-1b, TNF-a) in wound fluid expressed in pg/ml [ Time Frame: up to 4 weeks postoperatively ]
    compared using exact Wilcoxon rank sum tests
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE MicroRNA and MicroRNA Inhibitors Socket Study, Pilot Clinical Trial
Official Title  ICMJE 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Health Services Research
Condition  ICMJE Tooth Extraction Status Nos
Intervention  ICMJE
  • 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 Name: local infiltrative anesthesia
  • 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
    Other Name: Bovine collagen
  • 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
    Other Name: pSil-miR-200C plasmids
  • 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
    Other Name: PMIS miR200a plasmids
  • 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
    Other Name: 5µg of pSil-miR200c and 5µg of PMIS miR200a plasmids
  • 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 Name: venipuncture
  • 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.
Study Arms  ICMJE
  • Placebo Comparator: 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.
    Interventions:
    • Procedure: tooth extraction
    • Radiation: CBCT scan
    • Drug: Anesthesia
    • Other: clinical measurements
    • Drug: Biodegradable sponge (type I bovine collagen)
    • Procedure: cross mattress suture
    • Procedure: Blood
    • Other: Photos/videos
    • Procedure: Wound fluid
    • Procedure: saliva
    • Radiation: periapical xray
    • Other: PVS impression
  • Active Comparator: 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.
    Interventions:
    • Procedure: tooth extraction
    • Radiation: CBCT scan
    • Drug: Anesthesia
    • Other: clinical measurements
    • Drug: 10µg of pSil-miR200c
    • Procedure: cross mattress suture
    • Procedure: Blood
    • Other: Photos/videos
    • Procedure: Wound fluid
    • Procedure: saliva
    • Radiation: periapical xray
    • Other: PVS impression
  • Active Comparator: 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.
    Interventions:
    • Procedure: tooth extraction
    • Radiation: CBCT scan
    • Drug: Anesthesia
    • Other: clinical measurements
    • Procedure: cross mattress suture
    • Drug: 10µg of PMIS miR200a plasmids
    • Procedure: Blood
    • Other: Photos/videos
    • Procedure: Wound fluid
    • Procedure: saliva
    • Radiation: periapical xray
    • Other: PVS impression
  • Active Comparator: 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.
    Interventions:
    • Procedure: tooth extraction
    • Radiation: CBCT scan
    • Drug: Anesthesia
    • Other: clinical measurements
    • Procedure: cross mattress suture
    • Drug: 5µg of pSil-miR200c and 5µg of PMIS miR200a
    • Procedure: Blood
    • Other: Photos/videos
    • Procedure: Wound fluid
    • Procedure: saliva
    • Radiation: periapical xray
    • Other: PVS impression
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Withdrawn
Actual Enrollment  ICMJE
 (submitted: July 15, 2019)
0
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2015)
10
Estimated Study Completion Date  ICMJE September 2030
Estimated Primary Completion Date September 2030   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 25 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02579187
Other Study ID Numbers  ICMJE 201607780
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Gustavo Avila-Ortiz DDS, MS, PhD, University of Iowa
Study Sponsor  ICMJE Gustavo Avila-Ortiz DDS, MS, PhD
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Brad Amendt, MS UIowa College of Dentistry
PRS Account University of Iowa
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP