Clinical trial NCT06041178: Flurbiprofen Versus Aloe Vera Gel in the Treatment of Chronic Periodontitis in Smoking Patients.
Official title: Efficiency of Flurbiprofen 2.5% in Comparison to 98% Aloe Vera Gel as an Adjunctive Therapy to Scaling and Root Planning in the Initial Treatment of Stage III Chronic Periodontitis in Smoking Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Periodontitis Chronic Generalized Severe
Lead sponsor: Beirut Arab University
Sponsor class: OTHER
First posted: 2023-09-18
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: This study aims to evaluate clinically the efficacy of flurbiprofen gel in comparison to Aloe Vera gel as adjunctive to SRP in the reduction of periodontal pockets in patients with chronic periodontitis in smoking patients.

All patients will receive SRP prior to treatment.

* Group 1: one site will receive flurbiprofen while the contralateral site will receive a placebo
* Group 2: one site will receive aloe vera while the contralateral site will receive a placebo
* Group 3: one site will receive flurbiprofen while the contralateral site will receive aloe vera Researchers will compare the inter and intra-groups differences to check if there's a variation in the periodontal parameters measured.

Detailed description: Complete medical and dental histories as well as informed consent will be collected from eligible participants, and periodontal charting will be done for them.

Medical history and laboratory screening for all patients will be carried out at baseline. All participants will undergo scaling and root planning. The selected patients will be allocated into three groups with the help of a computerized randomizer (Randomizer.org) and sites will be assigned as control or test based on a coin flip method:

* Group 1 (G1): 20 patients who received treatment involving the application of flurbiprofen gel as an adjunct to scaling and root planing. Specifically, on the test site of each patient, one milliliter of 2.5% flurbiprofen gel was applied, while on the contralateral side, placebo gel was administered as the control intervention.
* Group 2 (G2): 20 patients who received treatment involving the application of aloe Vera gel as an adjunct to scaling and root planing. Specifically, on the test site of each patient, one milliliter of 98% aloe Vera was applied, while on the contralateral side, placebo gel was administered as the control intervention.
* Group 3 (G3): The intervention involved applying flurbiprofen gel on one site, while the contralateral side received an application of 98% aloe vera.

The clinical examiner will not be informed of the treatment groups' distribution.

Patients will be informed on self-performed plaque control measures. In the 4th week, 8th week, 12th week, 6 months week clinical examination will be performed to measure the periodontal pocket depth, gingival index, plaque index, clinical attachment level (CAL),and bleeding on probing.

Statistical analysis was done using SAS 9.4 Software (SAS Institute Inc., Cary, NC, USA). Means and standard deviations (SD) were calculated for all continuous variables (periodontal parameters: CAL, PD, BOP, GI, PI) at the baseline, fourth week, eighth week, and twelfth week and 6 months. Repeated linear mixed-effects models (PROC MIXED in SAS) were used to examine the changes in all periodontal parameters over the five-time points within each group and between groups. An unstructured covariance matrix was used, residual plots were visually reviewed to check model fit, and extreme outliers were eliminated using the restricted likelihood distance. A Tukey-Kramer 8 correction was applied to all pairwise comparisons. One-way ANOVA was used to examine group differences in PD reduction and CAL. A p-value of 0.05 was considered statistically significant.

Eligibility criteria: Inclusion criteria: 60 patients were selected who had clinical periodontal loss and radiographic bone loss of stage III/grade C with no history of systemic disease. They had at least 2 periodontal sites with a pocket depth of six mm or greater, radiographic evidence of bone loss extending to the middle third of the root, and clinical attachment loss of five mm or more. Eligible subjects were categorized as current smokers if they consistently smoked more than 10 cigarettes per day for a minimum of 5 years. Additionally, individuals with no record of undergoing any periodontal treatment within the six months preceding the study were considered for inclusion.

Exclusion criteria: Patients with systemic illnesses such as diabetes mellitus or conditions that could potentially impair wound healing were excluded from participation. Additionally, individuals who were pregnant or lactating were not considered for inclusion in the study. Subjects who had been prescribed systemic antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs) within the three months preceding the study were also excluded. Furthermore, individuals with confirmed or suspected hypersensitivity to Flurbiprofen or aloe Vera, the focus of the investigation, were not included in the study population.

Primary outcomes:
measure: clinical attachment level
timeFrame: 6 months
measure: Probing Depth
timeFrame: 6 months
Secondary outcomes:
measure: Bleeding on Probing
timeFrame: 6 months
measure: Plaque index
timeFrame: 6 months
measure: Gingival index
timeFrame: 6 months
Other outcomes:
Locations:
city: Beirut
country: Lebanon
facility: Beirut Arab University
Study officials:
affiliation: Professor and Chairman of Periodontology department - BeirutArabU
name: Nayer Aboelsaad, PhD
role: STUDY_CHAIR
References:
citation: Zhang S, Yu N, Arce RM. Periodontal inflammation: Integrating genes and dysbiosis. Periodontol 2000. 2020 Feb;82(1):129-142. doi: 10.1111/prd.12267.
citation: Sanchavanakit N, Saengtong W, Manokawinchoke J, Pavasant P. TNF-alpha stimulates MMP-3 production via PGE2 signalling through the NF-kB and p38 MAPK pathway in a murine cementoblast cell line. Arch Oral Biol. 2015 Jul;60(7):1066-74. doi: 10.1016/j.archoralbio.2015.04.001. Epub 2015 Apr 20.
citation: Offenbacher S, Farr DH, Goodson JM. Measurement of prostaglandin E in crevicular fluid. J Clin Periodontol. 1981 Aug;8(4):359-67. doi: 10.1111/j.1600-051x.1981.tb02045.x.
citation: Khan KM, Kothari P, Du B, Dannenberg AJ, Falcone DJ. Matrix metalloproteinase-dependent microsomal prostaglandin E synthase-1 expression in macrophages: role of TNF-alpha and the EP4 prostanoid receptor. J Immunol. 2012 Feb 15;188(4):1970-80. doi: 10.4049/jimmunol.1102383. Epub 2012 Jan 6.
citation: Eke PI, Wei L, Thornton-Evans GO, Borrell LN, Borgnakke WS, Dye B, Genco RJ. Risk Indicators for Periodontitis in US Adults: NHANES 2009 to 2012. J Periodontol. 2016 Oct;87(10):1174-85. doi: 10.1902/jop.2016.160013. Epub 2016 Jul 1.
citation: Kim J, Amar S. Periodontal disease and systemic conditions: a bidirectional relationship. Odontology. 2006 Sep;94(1):10-21. doi: 10.1007/s10266-006-0060-6.
citation: Ehizele A, Akhionbare O. Effect of non-surgical periodontal therapy on the concentration of volatile sulfur compound in mouth air of a group of nigerian young adults. Ann Med Health Sci Res. 2013 Jul;3(3):433-7. doi: 10.4103/2141-9248.117951.
citation: Choi YM, Lee JY, Choi J, Joo JY. Effect of root planing on the reduction of probing depth and the gain of clinical attachment depending on the mode of interproximal bone resorption. J Periodontal Implant Sci. 2015 Oct;45(5):184-9. doi: 10.5051/jpis.2015.45.5.184. Epub 2015 Nov 2.
citation: Morozumi T, Kubota T, Abe D, Shimizu T, Nohno K, Yoshie H. Microbiological effect of essential oils in combination with subgingival ultrasonic instrumentation and mouth rinsing in chronic periodontitis patients. Int J Dent. 2013;2013:146479. doi: 10.1155/2013/146479. Epub 2013 Sep 19.
citation: Goodson JM, Dewhirst FE, Brunetti A. Prostaglandin E2 levels and human periodontal disease. Prostaglandins. 1974 Apr 10;6(1):81-5. doi: 10.1016/s0090-6980(74)80043-2. No abstract available.
citation: Bacchi S, Palumbo P, Sponta A, Coppolino MF. Clinical pharmacology of non-steroidal anti-inflammatory drugs: a review. Antiinflamm Antiallergy Agents Med Chem. 2012;11(1):52-64. doi: 10.2174/187152312803476255.
citation: Ren J, Fok MR, Zhang Y, Han B, Lin Y. The role of non-steroidal anti-inflammatory drugs as adjuncts to periodontal treatment and in periodontal regeneration. J Transl Med. 2023 Feb 25;21(1):149. doi: 10.1186/s12967-023-03990-2.
citation: Marcum ZA, Hanlon JT. Recognizing the Risks of Chronic Nonsteroidal Anti-Inflammatory Drug Use in Older Adults. Ann Longterm Care. 2010;18(9):24-27.
citation: Sholapurkar A, Sharma D, Glass B, Miller C, Nimmo A, Jennings E. Professionally Delivered Local Antimicrobials in the Treatment of Patients with Periodontitis-A Narrative Review. Dent J (Basel). 2020 Dec 22;9(1):2. doi: 10.3390/dj9010002.
citation: Salvi GE, Lang NP. The effects of non-steroidal anti-inflammatory drugs (selective and non-selective) on the treatment of periodontal diseases. Curr Pharm Des. 2005;11(14):1757-69. doi: 10.2174/1381612053764878.
citation: Howell TH, Fiorellini J, Weber HP, Williams RC. Effect of the NSAID piroxicam, topically administered, on the development of gingivitis in beagle dogs. J Periodontal Res. 1991 May;26(3 Pt 1):180-3. doi: 10.1111/j.1600-0765.1991.tb01643.x.
citation: Deshpande NC, Bhat KM, Bhat GS, Deshpande AN. Randomized, controlled clinical study to evaluate efficacy of novel indigenously designed controlled release flurbiprofen gel system for management of periodontal diseases. Contemp Clin Dent. 2013 Jan;4(1):32-6. doi: 10.4103/0976-237X.111591.
citation: Saglam M, Kantarci A, Dundar N, Hakki SS. Clinical and biochemical effects of diode laser as an adjunct to nonsurgical treatment of chronic periodontitis: a randomized, controlled clinical trial. Lasers Med Sci. 2014 Jan;29(1):37-46. doi: 10.1007/s10103-012-1230-0. Epub 2012 Nov 16.
citation: Pradeep AR, Bajaj P, Agarwal E, Rao NS, Naik SB, Kalra N, Priyanka N. Local drug delivery of 0.5% azithromycin in the treatment of chronic periodontitis among smokers. Aust Dent J. 2013 Mar;58(1):34-40. doi: 10.1111/adj.12019. Epub 2013 Jan 30.
citation: Agarwal E, Pradeep AR, Bajaj P, Naik SB. Efficacy of local drug delivery of 0.5% clarithromycin gel as an adjunct to non-surgical periodontal therapy in the treatment of current smokers with chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2012 Sep;83(9):1155-63. doi: 10.1902/jop.2012.110600. Epub 2012 Jan 16.
citation: Eick S, Renatus A, Heinicke M, Pfister W, Stratul SI, Jentsch H. Hyaluronic Acid as an adjunct after scaling and root planing: a prospective randomized clinical trial. J Periodontol. 2013 Jul;84(7):941-9. doi: 10.1902/jop.2012.120269. Epub 2012 Oct 22.
citation: Prasad D, Kunnaiah R. Punica granatum: A review on its potential role in treating periodontal disease. J Indian Soc Periodontol. 2014 Jul;18(4):428-32. doi: 10.4103/0972-124X.138678.
citation: Krayer JW, Leite RS, Kirkwood KL. Non-surgical chemotherapeutic treatment strategies for the management of periodontal diseases. Dent Clin North Am. 2010 Jan;54(1):13-33. doi: 10.1016/j.cden.2009.08.010.
citation: Eid Abdelmagyd HA, Ram Shetty DS, Musa Musleh Al-Ahmari DM. Herbal medicine as adjunct in periodontal therapies- A review of clinical trials in past decade. J Oral Biol Craniofac Res. 2019 Jul-Sep;9(3):212-217. doi: 10.1016/j.jobcr.2019.05.001. Epub 2019 May 14.
citation: Taleghani F, Rezvani G, Birjandi M, Valizadeh M. Impact of green tea intake on clinical improvement in chronic periodontitis: A randomized clinical trial. J Stomatol Oral Maxillofac Surg. 2018 Nov;119(5):365-368. doi: 10.1016/j.jormas.2018.04.010. Epub 2018 Apr 30.
citation: Mekhemar M, Geib M, Kumar M, Radha, Hassan Y, Dorfer C. Salvadora persica: Nature's Gift for Periodontal Health. Antioxidants (Basel). 2021 Apr 30;10(5):712. doi: 10.3390/antiox10050712.
citation: Vogler BK, Ernst E. Aloe vera: a systematic review of its clinical effectiveness. Br J Gen Pract. 1999 Oct;49(447):823-8.
citation: Harlev E, Nevo E, Lansky EP, Ofir R, Bishayee A. Anticancer potential of aloes: antioxidant, antiproliferative, and immunostimulatory attributes. Planta Med. 2012 Jun;78(9):843-52. doi: 10.1055/s-0031-1298453. Epub 2012 Apr 19.
citation: Pareek S, Nagaraj A, Sharma P, Atri M, Walia S, Naidu S, Yousuf A. Disinfection of dental unit water line using aloe vera: in vitro study. Int J Dent. 2013;2013:618962. doi: 10.1155/2013/618962. Epub 2013 Sep 8.
citation: Im SA, Kim KH, Kim HS, Lee KH, Shin E, Do SG, Jo TH, Park YI, Lee CK. Processed Aloe vera gel ameliorates cyclophosphamide-induced immunotoxicity. Int J Mol Sci. 2014 Oct 24;15(11):19342-54. doi: 10.3390/ijms151119342.
citation: Athiban PP, Borthakur BJ, Ganesan S, Swathika B. Evaluation of antimicrobial efficacy of Aloe vera and its effectiveness in decontaminating gutta percha cones. J Conserv Dent. 2012 Jul;15(3):246-8. doi: 10.4103/0972-0707.97949.
citation: Doddanna SJ, Patel S, Sundarrao MA, Veerabhadrappa RS. Antimicrobial activity of plant extracts on Candida albicans: an in vitro study. Indian J Dent Res. 2013 Jul-Aug;24(4):401-5. doi: 10.4103/0970-9290.118358.
citation: Babaee N, Zabihi E, Mohseni S, Moghadamnia AA. Evaluation of the therapeutic effects of Aloe vera gel on minor recurrent aphthous stomatitis. Dent Res J (Isfahan). 2012 Jul;9(4):381-5.
citation: Pradeep AR, Agarwal E, Naik SB. Clinical and microbiologic effects of commercially available dentifrice containing aloe vera: a randomized controlled clinical trial. J Periodontol. 2012 Jun;83(6):797-804. doi: 10.1902/jop.2011.110371. Epub 2011 Nov 16.
citation: Namiranian H, Serino G. The effect of a toothpaste containing aloe vera on established gingivitis. Swed Dent J. 2012;36(4):179-85.
citation: Chandrahas B, Jayakumar A, Naveen A, Butchibabu K, Reddy PK, Muralikrishna T. A randomized, double-blind clinical study to assess the antiplaque and antigingivitis efficacy of Aloe vera mouth rinse. J Indian Soc Periodontol. 2012 Oct;16(4):543-8. doi: 10.4103/0972-124X.106905.
citation: Ashouri Moghaddam A, Radafshar G, Jahandideh Y, Kakaei N. Clinical Evaluation of Effects of Local Application of Aloe vera Gel as an Adjunct to Scaling and Root Planning in Patients with Chronic Periodontitis. J Dent (Shiraz). 2017 Sep;18(3):165-172.
citation: Nayer Aboelsaad, et al. (2014) Clinical Efficacy of Local Delivered Minocycline in the Treatment of Chronic Periodontitis Smoker Patients. J Dent Oral Health 1: 1-5
citation: Brad W. Neville DDS, ... Angela C. Chi DMD, in Color Atlas of Oral and Maxillofacial Diseases, 2019