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出境医 / 临床实验 / Connection Between Periodontitis and Exudative Age-related Macular Degeneration (FLAREPARO)

Connection Between Periodontitis and Exudative Age-related Macular Degeneration (FLAREPARO)

Study Description
Brief Summary:
Aqueous flare is increased in different kind of inflammations of eye. This is caused by disruption of blood-aqueous-barrier. The investigators assume that low grade systemic inflammation, such as periodontitis, increase aqueous flare and possibly activates exudative age-related macular degeneration.

Condition or disease Intervention/treatment Phase
Periodontitis Procedure: Anti-infective treatment of periodontal pockets Not Applicable

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Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Connection Between Periodontitis and Exudative Age-related Macular Degeneration
Actual Study Start Date : January 1, 2020
Estimated Primary Completion Date : June 1, 2022
Estimated Study Completion Date : June 1, 2022
Arms and Interventions
Arm Intervention/treatment
Calculus removement
Anti-infective treatment of teeth
Procedure: Anti-infective treatment of periodontal pockets
Removing calculi from teeths' periodontal pockets

Outcome Measures
Primary Outcome Measures :
  1. <10pu/msec to over 300pu/msec [ Time Frame: Change from Baseline aqueous flare value at 6 weeks ]
    Aqueous flare value before (in the same day) and after 6 weeks of anti-infective treatment of teeth


Eligibility Criteria
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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • periodontitis

Exclusion Criteria:

  • no periodontitis, any eye disease
Contacts and Locations

Contacts
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Contact: Petteri Karesvuo, M.D. +358 9 4711 petteri.karesvuo@helsinki.fi
Contact: Raimo Tuuminen, PhD raimo.tuuminen@helsinki.fi

Locations
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Finland
Kymeenlaakson keskussairaala Recruiting
Kotka, Finland
Contact: Sam Häyry    +358 (0)5 220 51      
Sponsors and Collaborators
University of Helsinki
Investigators
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Study Chair: Raimo Tuuminen, PhD Helsinki Retina Research Group
Tracking Information
First Submitted Date  ICMJE May 15, 2019
First Posted Date  ICMJE May 22, 2019
Last Update Posted Date September 1, 2020
Actual Study Start Date  ICMJE January 1, 2020
Estimated Primary Completion Date June 1, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2019)
<10pu/msec to over 300pu/msec [ Time Frame: Change from Baseline aqueous flare value at 6 weeks ]
Aqueous flare value before (in the same day) and after 6 weeks of anti-infective treatment of teeth
Original Primary Outcome Measures  ICMJE
 (submitted: May 17, 2019)
<10pu/msec to over 300pu/msec [ Time Frame: 1.6.2019-1.6.2020 ]
Aqueous flare value before and after 6 weeks of anti-infective treatment of teeth
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Connection Between Periodontitis and Exudative Age-related Macular Degeneration
Official Title  ICMJE Connection Between Periodontitis and Exudative Age-related Macular Degeneration
Brief Summary Aqueous flare is increased in different kind of inflammations of eye. This is caused by disruption of blood-aqueous-barrier. The investigators assume that low grade systemic inflammation, such as periodontitis, increase aqueous flare and possibly activates exudative age-related macular degeneration.
Detailed Description

Periodontitis is a chronic low-grade bacterial infection of supporting tissue of teeth. Chronic periodontitis is often non symptomatic. Inflammation is located usually in deepened periodontal pockets (> 4mm or >6mm) and it leads to alveolar bone loss and eventually detachment of teeth. In Finland, it is estimated that 64% of people have mild form of periodontitis and severe form approximately 21% according to Health 2000 and Health 2011 studies. Various gram negative and positive pathogens have been isolated in infected area, Porhyromonas Gingivalis, Prevotella intermedia, Treponema denticola, Tannerella forsynthesis, Campylobacter rectus, Aggregatibacter actinomycetemcomitans and Peptostreoptococcus micros. Periodontitis causes endotoxemia in circulation via inflamed supporting structure of teeth. Endotoxins such as lipopolysaccharide (LPS) and their concentrations are elevated in blood and it is found that C-reactive protein (CRP), interleukins and cytokines are also elevated in blood due to periodontitis. As a result periodontitis activates low-grade systemic inflammation and complement system activation classical and alternative pathway. In some studies, the treatment of periodontitis diminished CRP values and lowered the systemic inflammation. Periodontitis has been connected with many diseases, such as atherosclerosis, coronary artery disease, Alzheimer's disease and adverse pregnancy outcomes. Furthermore, various studies have found association between periodontitis and age-related macular degeneration. Severity of diabetic retinopathy was linked with severity of periodontitis furthermore scleritis was resoluted after periodontal treatment Aqueous flare is a hallmark of blood-aqueous-barrier. Increased aqueous flare is found in different types of inflammations and infections of eye for example in iritis and in endophthalmitis. In addition intraocular surgery promotes almost always aqueous flare postoperatively. Increased aqueous flare and macular thickening and postoperative cystoid macular edema (PCME) are found after uneventful cataract operation. The higher flare levels correlated with the activity in wet age-related macular degeneration and in addition in central retinal vein occlusion.

Here in this study the investigators aimed to characterize the association between the periodontitis and elevated aqueous flare values as a potential risk factor for developing exudative macular degeneration.

Material and methods Study will be conducted at Kymenlaakso Central Hospital in Kotka, Finland. Time period is going to be between 1.6.2019-1.6.2021. One hundred participents will be enrolled in this study calculated with power analysis (0.8). Drop-out patients will be about 5%. The investigators will measure periodontal pockets (>4mm or >6mm) and number of affected teeth and give anti-infective treatment in addition to taking bacterial PCR samples. Follow up visits will be after 6 weeks.

Non-invasive and safe aqueous flare measurements will be performed by investigators with aqueous flare meter (FM-600 Kowa Company, Ltd., Nagoya, Japan) before and 1 hour after anti-infective treatment. The flare values varies between < 10 photon units pu/msec in healthy subjects without BAB disruption and over 300 pu/msec in eyes with severe BAB disruption. Automated reliability analysis of the measurements performed by the laser flare meter will be taken into account. The patient information will be stored in a password protected computer and no one else outside the study is not allowed to participate the study and process the data. Study material will be processed in a HUS computer or in a password protected personal computer via VPN communication link. Helsinki University Helpdesk will offer user interface. Participents personal infromation will be deleted after usage and anonymous registry and data will be stored for 5 years in a digital password protected SSD memory after the publication of the study findings.

Ethical perspectives The treatment models used in the study comply with Good Clinical Practice. The patient will be provided with both verbal and written information before signing the consent form. Study subjects may withdraw their consent after the study has begun. The study will have no effect in any way on the care that the patient receives. Information about the study subject and the results obtained from the study will be handled confidentially. The study aims to provide the latest definitive results, nor can it be conducted in any other way. The study may have a significant benefit on understanding wet AMD pathophysiology. The study will follow the principles of the Declaration of Helsinki of the World Medical Association.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Periodontitis
Intervention  ICMJE Procedure: Anti-infective treatment of periodontal pockets
Removing calculi from teeths' periodontal pockets
Study Arms  ICMJE Calculus removement
Anti-infective treatment of teeth
Intervention: Procedure: Anti-infective treatment of periodontal pockets
Publications *
  • Shin YU, Lim HW, Hong EH, Kang MH, Seong M, Nam E, Cho H. The association between periodontal disease and age-related macular degeneration in the Korea National health and nutrition examination survey: A cross-sectional observational study. Medicine (Baltimore). 2017 Apr;96(14):e6418. doi: 10.1097/MD.0000000000006418.
  • Wagley S, Marra KV, Salhi RA, Gautam S, Campo R, Veale P, Veale J, Arroyo JG. PERIODONTAL DISEASE AND AGE-RELATED MACULAR DEGENERATION: Results From the National Health and Nutrition Examination Survey III. Retina. 2015 May;35(5):982-8. doi: 10.1097/IAE.0000000000000427.
  • Karesvuo P, Gursoy UK, Pussinen PJ, Suominen AL, Huumonen S, Vesti E, Könönen E. Alveolar bone loss associated with age-related macular degeneration in males. J Periodontol. 2013 Jan;84(1):58-67. doi: 10.1902/jop.2012.110643. Epub 2012 Mar 13.

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 17, 2019)
95
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2022
Estimated Primary Completion Date June 1, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • periodontitis

Exclusion Criteria:

  • no periodontitis, any eye disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Petteri Karesvuo, M.D. +358 9 4711 petteri.karesvuo@helsinki.fi
Contact: Raimo Tuuminen, PhD raimo.tuuminen@helsinki.fi
Listed Location Countries  ICMJE Finland
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03958461
Other Study ID Numbers  ICMJE HRRG FLAREPARO
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Petteri Karesvuo, University of Helsinki
Study Sponsor  ICMJE University of Helsinki
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Raimo Tuuminen, PhD Helsinki Retina Research Group
PRS Account University of Helsinki
Verification Date August 2020

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