Clinical trial NCT06070311: Wound Healing After Endoscopic Sinus Surgery
Official title: Effect of Thymoquinone and Olive Oil on Wound Healing After Endoscopic Sinus Surgery in Patients With Nasal Polyposis
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Nasal Polyps
Chronic Sinusitis
Lead sponsor: Assiut University
Sponsor class: OTHER
First posted: 2023-10-06
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study aims to determine the effect of Thymoquinone (0.5%) and olive oil ointment on Wound healing after Endoscopic sinus surgery.

Detailed description: Endoscopic sinus surgery (ESS) has become a widely accepted procedure for medically refractory chronic rhino sinusitis and nasal polyps. Over 250,000 endoscopic sinus surgeries are performed yearly in the United States alone, however, postoperative complications and disease recurrence requiring revision surgery are reported in 14% to 24% of patients in long-term follow-up.

There is an increasing interest in interventions and therapies targeted at optimizing outcomes and preventing revision surgery which often depends on good wound healing and less adhesion formation.

The choice of appropriate post-surgical topical treatments is important for healing time and for preventing mucosal complications such as adhesions, crusting formation, and atrophy with secondary bacterial and fungal infections in this light this study aims to determine the effect of thymoquinone and olive oil ointment on wound healing after ESS.

Thymoquinone (TQ) is the most abundant constituent of the volatile oil of Nigella sativa seeds and most properties of Nigella sativa are mainly attributed to TQ. Several pharmacological actions and therapeutic potentials of TQ have been investigated including being antioxidant, anti-inflammatory, antihistaminic, antimicrobial, anti-allergic, anti-fibrotic, and anti-cancer.

Olive oil plays an important role in wound healing process due to its content of phenolic compounds accelerating wound healing through their anti-inflammatory, antioxidant, and antimicrobial properties and their stimulation of angiogenic activities required for granulation tissue formation and wound re-epithelialization.

This Double Blinded Randomized Prospective Comparative study will follow patients with nasal polyposis who are indicated for endoscopic sinus surgery at the Department of Otorhinolaryngology in Assiut University Hospital during the period from the 1st of October 2023 to the 31st of September 2025.

At baseline (before surgery), a full medical history, an otorhinolaryngological examination, and pre-operative screening will be performed to ensure eligibility for the study. The patients will be informed about the surgical procedures, the potential risks of the surgery, and the aim and methodology of the study.

(A) Preoperative:

Full history taking:

1. Personal History
2. History of Sino-nasal symptoms e.g., nasal obstruction, nasal discharge, headache, hyposmia, facial congestion, etc.
3. Other ENT symptoms
4. General symptoms e.g., asthma, allergy, etc.
5. Medical history e.g., steroids, antibiotics, anticholinergics, etc.
6. History of nasal surgery
7. SNOT 22 questionnaire: To assess preoperative severity of symptoms.

Full medical examination:

1. General examination
2. Full ENT examination
3. Nasal Endoscopy:

   * To evaluate polyp size, site, extent, and consistency.

Investigations:

1. Routine preoperative investigations: CBC, prothrombin time and concentration
2. Radiological investigations: Multi-slice CT scan of the nose and paranasal sinuses axial and coronal cuts without contrast and each patient will be scored according to Lund-Mackay CT scoring.

Preparation of the Thymoquinone and Olive oil ointment:

Thymoquinone Oleaginous base ointment containing olive oil will be prepared for intranasal administration. The ointment will be prepared using the fusion method as follows:

Anhydrous lanolin and white soft paraffin will be melted at 70°C and then olive oil will be added with continuous stirring, Thymoquinone will be added to the congealing mixture as it is being cooled and stirred finally, the congealing mixture is left to cool at room temperature tell solidification and sterilized using UV radiation. The final product will be characterized for spreadability, drug content, drug release and stability.

(B) Intraoperative: All cases will be performed under general anaesthesia and the ESS procedure performed by the senior author is that defined by Kennedy.

Immediately after performing the ESS, Thymoquinone and olive oil Ointment will be applied to fill the ethmoidal and different sinuses cavities of one randomly chosen side of the nose, the selected side will be chosen randomly using the following online randomizer tool:

Randomizer \| Random Name/Number Picker - AnnaBet.com Then nasal packing with nasal sponge will be done for both sides.

(C) Postoperative: Patients will attend routine follow-up at 1, 2,3,4,8 and 12 weeks after surgery. At these visits, an endoscopic inspection will be performed, and the patients will undergo debridement of the ethmoid cavities when necessary. In addition, endoscopic data regarding the health of the Sino nasal mucosa will be collected. An independent investigator blinded to the side of TQ, and olive oil ointment placement will assess and compare the wound healing in both sides regarding adhesions, crust formation, granulation, infection and score each item using the scoring mentioned below.

Crust formation:

0: No crust formation observed.

1. Thin and easily removable crusts.
2. Moderate crust formation, requiring gentle removal.
3. Thick and adherent crusts, requiring careful and meticulous removal.

Adhesions:

0: No adhesions observed.

1. Mild adhesions, limited to small areas.
2. Moderate adhesions, affecting larger areas but without complete obstruction.
3. Severe adhesions, causing significant obstruction and impaired sinus drainage. 3.Granulation:

0: No granulations observed.

1. Mild granulation tissue, with minimal vascularity and minimal elevation.
2. Moderate granulation tissue, with moderate vascularity and noticeable elevation.
3. Severe granulation tissue, with marked vascularity and significant elevation. 4.Infection:

0: No signs or symptoms of infection observed.

1. Mild infection, mucopurulent discharge limited to small area of the ethmoidal cavity.
2. Moderate infection, mucopurulent discharge filling one sinus.
3. Severe infection, mucopurulent discharge filling more than one sinus.

Participants will take the SNOT-22 questionnaire after the operation at the follow up visits to evaluate sino nasal symptoms.

Eligibility criteria: Inclusion Criteria:

- All patients who will be clinically diagnosed and radiologically confirmed cases with bilateral nasal polyposis indicated for Endoscopic sinus surgery.

Exclusion Criteria:

1. Unfit patient for surgery
2. Pregnant and lactating women.
3. Patients unwilling to participate.
4. Patients who have unilateral disease.
5. Patients with a history of the following underlying medical conditions, which are associated with an increased rate of revision surgery, will be excluded from the study:

   1. Aspirin intolerance
   2. Asthma
   3. Mucociliary disorder
   4. Immunocompromised status.
6. Patients with known allergic reactions to Thymoquinone or olive oil.
7. Injury of the orbit with any tear in the periorbital area.

Primary outcomes:
measure: Determining the effectiveness of Thymoquinone (0.5%) and olive oil on Wound healing after Endoscopic sinus surgery regarding crust formation by Endoscopic examination.
timeFrame: Patients will attend routine follow-up at 1, 2,3,4,8 and 12 weeks after surgery
measure: Determining the effectiveness of Thymoquinone (0.5%) and olive oil on Wound healing after Endoscopic sinus surgery regarding adhesions by Endoscopic examination.
timeFrame: Patients will attend routine follow-up at 1, 2,3,4,8 and 12 weeks after surgery
measure: Determining the effectiveness of Thymoquinone (0.5%) and olive oil on Wound healing after Endoscopic sinus surgery regarding granulation formation by Endoscopic examination
timeFrame: Patients will attend routine follow-up at 1, 2,3,4,8 and 12 weeks after surgery
measure: Determining the effectiveness of Thymoquinone (0.5%) and olive oil on Wound healing after Endoscopic sinus surgery regarding infection by Endoscopic examination.
timeFrame: Patients will attend routine follow-up at 1, 2,3,4,8 and 12 weeks after surgery
Secondary outcomes:
measure: Evaluation of symptoms of CRS and NP after Endoscopic Sinus Surgery using SNOT22 questionnaire.
timeFrame: Patients will attend routine follow-up at 1, 2,3,4,8 and 12 weeks after surgery
Other outcomes:
Locations:
Study officials:
affiliation: Assiut University
name: Mohamed Mostafa Osman, Professor
role: STUDY_CHAIR
affiliation: Assiut University
name: Ahmed Gamal Sholkamy, Doctor
role: STUDY_DIRECTOR
affiliation: Assiut University
name: Tarek Ashraf, Doctor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Alobid I, Anton E, Armengot M, Chao J, Colas C, del Cuvillo A, Davila I, Dordal MT, Escobar C, Fernandez-Parra B, Gras-Cabrerizo JR, Ibanez MD, Lluch M, Mateu V, Montoro J, Gili JR, Mullol J, Navarro AM, Pumarola F, Rondon C, Sanchez-Hernandez MC, Sarandeses A, Soler R, Valero AL; Rhinoconjunctivitis Committee; Spanish Society of Allergy and Clinical Immunology; Rhinology and Allergy Commission; Spanish Society of Otorhinolaryngology. SEAIC-SEORL. Consensus Document on Nasal Polyposis. POLINA Project. J Investig Allergol Clin Immunol. 2011;21 Suppl 1:1-58. No abstract available.
citation: Hastan D, Fokkens WJ, Bachert C, Newson RB, Bislimovska J, Bockelbrink A, Bousquet PJ, Brozek G, Bruno A, Dahlen SE, Forsberg B, Gunnbjornsdottir M, Kasper L, Kramer U, Kowalski ML, Lange B, Lundback B, Salagean E, Todo-Bom A, Tomassen P, Toskala E, van Drunen CM, Bousquet J, Zuberbier T, Jarvis D, Burney P. Chronic rhinosinusitis in Europe--an underestimated disease. A GA(2)LEN study. Allergy. 2011 Sep;66(9):1216-23. doi: 10.1111/j.1398-9995.2011.02646.x. Epub 2011 May 24.
citation: Stevens WW, Schleimer RP, Kern RC. Chronic Rhinosinusitis with Nasal Polyps. J Allergy Clin Immunol Pract. 2016 Jul-Aug;4(4):565-72. doi: 10.1016/j.jaip.2016.04.012.
citation: Bachert C, Bhattacharyya N, Desrosiers M, Khan AH. Burden of Disease in Chronic Rhinosinusitis with Nasal Polyps. J Asthma Allergy. 2021 Feb 11;14:127-134. doi: 10.2147/JAA.S290424. eCollection 2021.
citation: Sari H, Karaketir S, Kumral TL, Akgun MF, Gurpinar B, Hanci D, Berkiten G, Uyar Y. The effect of platelet-rich fibrin (PRF) on wound healing, adhesion, and hemostasis after endoscopic sinus surgery in patients with nasal polyposis. Am J Otolaryngol. 2021 Sep-Oct;42(5):103010. doi: 10.1016/j.amjoto.2021.103010. Epub 2021 Mar 29.
citation: Soler ZM, Smith TL. Endoscopic sinus surgery checklist. Laryngoscope. 2012 Jan;122(1):137-9. doi: 10.1002/lary.22430. Epub 2011 Nov 17.
citation: Loftus CA, Soler ZM, Koochakzadeh S, Desiato VM, Yoo F, Nguyen SA, Schlosser RJ. Revision surgery rates in chronic rhinosinusitis with nasal polyps: meta-analysis of risk factors. Int Forum Allergy Rhinol. 2020 Feb;10(2):199-207. doi: 10.1002/alr.22487. Epub 2019 Nov 21.
citation: Testa D, Marcuccio G, Panin G, Bianco A, Tafuri D, Thyrion FZ, Nunziata M, Piombino P, Guerra G, Motta G. Nasal mucosa healing after endoscopic sinus surgery in chronic rhinosinusitis of elderly patients: role of topic alpha-tocopherol acetate. Aging Clin Exp Res. 2017 Feb;29(Suppl 1):191-195. doi: 10.1007/s40520-016-0647-x. Epub 2016 Nov 25.
citation: Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015 May-Jun;95-96:138-58. doi: 10.1016/j.phrs.2015.03.011. Epub 2015 Mar 28.
citation: Melguizo-Rodriguez L, de Luna-Bertos E, Ramos-Torrecillas J, Illescas-Montesa R, Costela-Ruiz VJ, Garcia-Martinez O. Potential Effects of Phenolic Compounds That Can Be Found in Olive Oil on Wound Healing. Foods. 2021 Jul 15;10(7):1642. doi: 10.3390/foods10071642.
citation: Hopkins C, Browne JP, Slack R, Lund V, Brown P. The Lund-Mackay staging system for chronic rhinosinusitis: how is it used and what does it predict? Otolaryngol Head Neck Surg. 2007 Oct;137(4):555-61. doi: 10.1016/j.otohns.2007.02.004.
citation: Kennedy DW. Functional endoscopic sinus surgery. Technique. Arch Otolaryngol. 1985 Oct;111(10):643-9. doi: 10.1001/archotol.1985.00800120037003.