Effects of Azithromycin as an Adjunct to Scaling and Root Planning in the Treatment of Periodontitis

NCT05506371 | Completed DMC

• 1 other identifier: 0122U00049
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

The growing interest in the possibilities of modulating macrophages in inflammatory diseases with therapeutic purpose has prompted the development of new approaches for the treatment of periodontitis. This randomized add-on open clinical study evaluated the short-term effects of azithromycin (Az) as an adjunct to scaling and root planing (SRP) in patients with chronic periodontitis. The investigators measured periodontal parameters, and collected gingival biopsies from patients with periodontitis (P group, n=50) before and 1 month after scaling and root planning (SRP group, n=25), after scaling and root planning with oral azithromycin administration (Az group, n=25), and from periodontally healthy individuals (H group, n=25). The last served as a reference group. Macrophage subpopulations were identified through immunohistochemistry as single positive CD68+ and CD163+ cells. The levels of M1-, and M2-related cytokines (IL1-β, IL-6, IL-10, TGF-β) assay in the tissue culture medium was provided by ELISA. The data were statistically analyzed by appropriate methods. The null hypothesis tested was that L-arginine and L-ornithine have no influences on CD68+ and CD163+ Mφs densities.

Conditions

Periodontitis

Keywords

Azithromycin; M1 macrophages; M2 macrophages; Macrophages-targeted therapy; Periodontitis

Outcome Measures

Primary Outcomes (2)

• Change in clinical attachment loss (CAL)

  Mean CAL, measured at six periodontal sites around each tooth (including the third molars) to the nearest 1 mm

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

• Change in periodontal pocket depth (PPD)

  Mean periodontal pocket depth, measured at six periodontal sites around each tooth (including the third molars) to the nearest 1 mm

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

Secondary Outcomes (7)

• Change in bleeding on probing (BOP)

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

• Change in density of CD68+ macrophages

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

• Change in density of CD163+ macrophages

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

• Change in mean level of IL1-β in periodontitis-affected gingiva

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

• Change in mean level of IL-6 in periodontitis-affected gingiva

  The pre-treatment stage (T0) and 4 weeks ±5 days after the completion of SRP

Study Arms (3)

Az group

EXPERIMENTAL

Periodontitis patients, who underwent scaling and root planning (SRP) as one-stage full-mouth disinfection procedure and additionally received oral azithromycin ("Health" Pharmaceutical Company, Kharkiv, Ukraine) in a dose of 500 mg q.d. for 7 days, then 500 mg q.w. for the next 3 weeks

Drug: Az+SRP

SRP group

ACTIVE COMPARATOR

Periodontitis patients who underwent scaling and root planning (SRP) as one-stage full-mouth disinfection procedure.

Drug: SRP

H group

OTHER

Reference group. 25 healthy volunteers who underwent only diagnostics to confirm the clinical healthy state of the gingiva

Drug: No interventions

Interventions

Az+SRP DRUG

Azithromycin as an adjunct to scaling and root planning in the treatment of periodontitis

Also known as: Azithromicyn group

Az group

SRP DRUG

Scaling and root planning (SRP) treatment of periodontitis

Also known as: Periodontal conventional treatment group

SRP group

No interventions DRUG

Diagnostocs to confirm the healthy state of the gingiva

Also known as: Reference/periodontal health group

H group

Eligibility Criteria

• Age: 19 Years - 54 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Presence of more than 20 teeth (for each tooth, the probing pocket depth ≤3 mm
• Absence of clinical gingival inflammation at intact or reduced periodontium
• The presence of at least 15 natural teeth, at least 10 sites with the periodontal pocket depth (PPD) ≥4 mm, and/or clinical attachment loss of ≥4 mm at the same site, and satisfactory general health

You may not qualify if:

• Taking antibiotics or anti-inflammatory medications within the previous 3 months
• Periodontal therapy within the previous 6 months
• Purulent exudation from periodontal pockets
• Pregnancy or breastfeeding
• Severe, uncontrolled (decompensated) diseases of the internal organs, or neuropsychiatric disorders
• Other conditions that determined the patient's inability to understand the nature and possible consequences of the study

Sponsors & Collaborators

• Ukrainian Medical Stomatological Academy: lead

Study Sites (1)

Department of Postgraduate Education for Dentists of Poltava State Medical University,

Poltava, 36011, Ukraine

Location

Related Publications (15)

• Morales A, Contador R, Bravo J, Carvajal P, Silva N, Strauss FJ, Gamonal J. Clinical effects of probiotic or azithromycin as an adjunct to scaling and root planning in the treatment of stage III periodontitis: a pilot randomized controlled clinical trial. BMC Oral Health. 2021 Jan 7;21(1):12. doi: 10.1186/s12903-020-01276-3.

  PMID: 33413320 BACKGROUND

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  PMID: 3860518 BACKGROUND

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  PMID: 25762997 BACKGROUND

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  PMID: 30285304 BACKGROUND

• Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT, Sahebkar A. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol. 2018 Sep;233(9):6425-6440. doi: 10.1002/jcp.26429. Epub 2018 Mar 1.

  PMID: 29319160 BACKGROUND

• Allam JP, Duan Y, Heinemann F, Winter J, Gotz W, Deschner J, Wenghoefer M, Bieber T, Jepsen S, Novak N. IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions. J Clin Periodontol. 2011 Oct;38(10):879-86. doi: 10.1111/j.1600-051X.2011.01752.x. Epub 2011 Aug 31.

  PMID: 21883359 BACKGROUND

• Fabriek BO, Dijkstra CD, van den Berg TK. The macrophage scavenger receptor CD163. Immunobiology. 2005;210(2-4):153-60. doi: 10.1016/j.imbio.2005.05.010.

  PMID: 16164022 BACKGROUND

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  PMID: 24631273 BACKGROUND

• Fujise O, Miura M, Hamachi T, Aida Y, Nishimura F. Regenerative effect of azithromycin on periodontitis with different levels of gingival inflammation: three case reports. Aust Dent J. 2014 Jun;59(2):245-51. doi: 10.1111/adj.12177.

  PMID: 24861402 BACKGROUND

• Nepokupnaia-Slobodianuk TS, Skripnikov PN. [The clinical effectiveness of long-term azithromycin in patients with chronic generalized periodontitis]. Georgian Med News. 2014 Nov;(236):27-31. Russian.

  PMID: 25541821 BACKGROUND

• Hai R, Chu A, Li H, Umamoto S, Rider P, Liu F. Infection of human cytomegalovirus in cultured human gingival tissue. Virol J. 2006 Oct 5;3:84. doi: 10.1186/1743-422X-3-84.

  PMID: 17022821 BACKGROUND

• Loos BG, Needleman I. Endpoints of active periodontal therapy. J Clin Periodontol. 2020 Jul;47 Suppl 22(Suppl 22):61-71. doi: 10.1111/jcpe.13253.

  PMID: 31912527 BACKGROUND

• Garaicoa-Pazmino C, Fretwurst T, Squarize CH, Berglundh T, Giannobile WV, Larsson L, Castilho RM. Characterization of macrophage polarization in periodontal disease. J Clin Periodontol. 2019 Aug;46(8):830-839. doi: 10.1111/jcpe.13156. Epub 2019 Jun 25.

  PMID: 31152604 BACKGROUND

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  PMID: 25340307 BACKGROUND

• Zhu LF, Li L, Wang XQ, Pan L, Mei YM, Fu YW, Xu Y. M1 macrophages regulate TLR4/AP1 via paracrine to promote alveolar bone destruction in periodontitis. Oral Dis. 2019 Nov;25(8):1972-1982. doi: 10.1111/odi.13167. Epub 2019 Oct 18.

  PMID: 31361069 BACKGROUND

MeSH Terms

Conditions

Periodontitis

Condition Hierarchy (Ancestors)

Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Igor P. Kaidashev, MD

  Ukrainian Medical Stomatological Academy Poltava, Ukraine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: All biopsies were reviewed by the same pathologist, blinded to experimental group affiliation of biopsies
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Honored Master of Science and Technology of Ukraine, Doctor of Medical Sciences, Professor Vice-Rector for Research and Development of Poltava State Medical University

Model Details: Randomized controlled short-term clinical trial

Study Record Dates

• First Submitted: August 14, 2022
• First Posted: August 18, 2022
• Study Start: September 16, 2017
• Primary Completion: June 28, 2019
• Study Completion: June 28, 2019
• Last Updated: October 31, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

UA (1)