Clinical trial NCT05369039: Roflumilust in Chronic Rhinosinusitis With Nasal Polyposis.
Official title: The Potential Therapeutic Effect of Roflumilust (a Selective Phosphodiesterase 4inhibitor) on Chronic Rhinosinusitis With Nasal Polyposis.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chronic Sinusitis
Keywords: Roflumilust
Chronic Sinusitis with nasal polyposis
Phosphodiesterase inhibitor
Lead sponsor: Menoufia University
Sponsor class: OTHER
First posted: 2022-05-11
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The current study will be a pilot study for a randomized controlled trial conducted on 60 patients recruited from the outpatient clinic of the Otorhinolaryngology Department, Menoufia Faculty of Medicine after approval of the institutional review board and taking informed written consent from every patient before participation in the study. The patients of this study will be randomly and equally distributed among case and control groups to compare the effect of Roflumilust administration with the effect of systemic and local corticosteroids on patients with chronic rhinosinusitis with nasal polyposis

Detailed description: The current study will be a pilot study for a randomized controlled trial conducted on 60 patients recruited from the outpatient clinic of the Otorhinolaryngology Department, Menoufia Faculty of Medicine after approval of the institutional review board and taking informed written consent from every patient before participation in the study. The patients of this study will be randomly and equally distributed among case and control groups.

To be included in the study, patients should be more than 18 years old, have chronic rhinosinusitis with nasal polyposis, and have no history of systemic steroid administration over the last three months. History of previous nasal surgery, underlying systemic diseases (like diabetes mellitus, hypertension, or autoimmune diseases), and hypersensitivity to Roflumilust were the exclusion criteria for this study.

Patients of the study will be randomly and equally distributed between case and control groups using block randomization methods using 4 blocks each comprising 4 patients with 6 patterns for every block one of which was selected randomly using random numbers generated by Excel program. The case group will receive a 10 days course of Roflumilust in a dose of 500 mg once daily. The Control group will receive a 10 days course of systemic steroids in the form of oral prednisolone in a dose of 40 mg per day.

Assessment protocol:

Patients of the study will be assessed before and at the end of the treatment protocol with history taking to define the inclusion and exclusion criteria and to assess the burden of nasal symptoms using SNOT-22 scale. Endoscopic examination of the nasal cavity will be performed to confirm the presence of bilateral nasal polyposis and to assess the degree of nasal polyposis using the Lund Kennedy score. Serum IL17 and periostin will be assessed using ELISA technique before and after treatment to assess the anti-inflammatory effects of the drug.

Outcome measures:

Primary outcome measures will include a comparison between the pre and post treatment values of SNOT-22 and Lund Kennedy scores, serum IL17, and serum priostin in both case and control groups. Another outcome measure will be the comparison between the case and control groups regarding the posttreatment and posttreatment values of the previous indices. Secondary outcome measures will include an assessment of the side effects of Roflumilust among the case group.

Eligibility criteria: Inclusion Criteria:

* chronic rhinosinusitis with nasal polyposis,
* No history of systemic steroid administration over the last three months

Exclusion Criteria:

* History of previous nasal surgery,
* Underlying systemic diseases (like diabetes mellitus, hypertension, or autoimmune diseases),
* Hypersensitivity to Roflumilust

Primary outcomes:
measure: Comparison between pretreatment and posttreatment SNOT-22 score in both groups
timeFrame: 2 weeks after start of treatment
measure: Comparison between pretreatment and posttreatment Lund Kennedy scores in both groups
timeFrame: Two weeks after start of treatment
measure: Comparison between pretreatment and posttreatment Serum periostin levels in both groups
timeFrame: Two weeks after start of treatment
measure: Comparison between case and control groups regarding SNOT 22 score
timeFrame: Two weeks after start of treatment
measure: Comparison between case and control groups regarding Lund Kennedy score
timeFrame: Two weeks after start of treatment
measure: Comparison between case and control groups regarding serum periostin level
timeFrame: Two weeks after start of treatment
Secondary outcomes:
measure: Assessment of the side effects of Roflumilust
timeFrame: Two weeks after start of treatment
Other outcomes:
Locations:
city: Shibīn Al Kawm
country: Egypt
facility: Menoufia Faculty of Medicine
state: Menoufia
Study officials:
References:
citation: Hulse KE, Stevens WW, Tan BK, Schleimer RP. Pathogenesis of nasal polyposis. Clin Exp Allergy. 2015 Feb;45(2):328-46. doi: 10.1111/cea.12472.
citation: Ryu G, Bae JS, Kim JH, Kim EH, Lyu L, Chung YJ, Mo JH. Role of IL-17A in Chronic Rhinosinusitis With Nasal Polyp. Allergy Asthma Immunol Res. 2020 May;12(3):507-522. doi: 10.4168/aair.2020.12.3.507.
citation: Maxfield AZ, Landegger LD, Brook CD, Lehmann AE, Campbell AP, Bergmark RW, Stankovic KM, Metson R. Periostin as a Biomarker for Nasal Polyps in Chronic Rhinosinusitis. Otolaryngol Head Neck Surg. 2018 Jan;158(1):181-186. doi: 10.1177/0194599817737967. Epub 2017 Oct 17.
citation: Janosova V, Calkovsky V, Pedan H, Behanova E, Hajtman A, Calkovska A. Phosphodiesterase 4 Inhibitors in Allergic Rhinitis/Rhinosinusitis. Front Pharmacol. 2020 Jul 22;11:1135. doi: 10.3389/fphar.2020.01135. eCollection 2020.
citation: Inagaki N, Miura T, Daikoku M, Nagai H, Koda A. Inhibitory effects of beta-adrenergic stimulants on increased vascular permeability caused by passive cutaneous anaphylaxis, allergic mediators, and mediator releasers in rats. Pharmacology. 1989;39(1):19-27. doi: 10.1159/000138567.