Clinical trial NCT01986582: NoAL (HPMC) in Combination With Oxymetazoline in Patients With Allergic Rhinitis
Official title: Stage 2, Double-blind, Randomized, Parallel Groups, One Centre Study in Patients With Allergic Rhinitis Treated With Nasal Oxymetazoline in Combination With Nasal Hydroxyl-propyl-methyl Cellulose (HPMC) or Placebo
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Allergic Rhinitis
Keywords: Allergic Rhinitis
Congestion
Mucoadhesive Treatment
Nasal Decongestant
Lead sponsor: Association Asthma, Bulgaria
Sponsor class: OTHER
Collaborators: name: Nasaleze
First posted: 2013-11-18
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Allergic rhinitis is treated with a variety of systemic and locally applied drugs. The effectiveness of the intranasally applied formulations is diminished by the cleaning mechanisms of the nose, rhinorrhea in particular. Slowing down of the clearance of the nasal mucosa and prolonging the contact time of locally applied drugs with the nasal mucosa would improve their efficacy. One method is creating dosage forms containing mucoadhesive polymers. We have demonstrated that a mucoadhesive solution containing HPMC enhances the clinical efficacy of oxymetazoline. However, the industrial development of fixed combinations of pharmaceutical compound and mucoadhesive carrier requires substantial investments, escalating manifold if different pharmaceutical compounds have to be rendered mucoadhesive.

NoAl is a cellulose derivative powder, which forms a gel layer on contact with the mucosal surface of the nose blocking the contact of the pollen grains with the nasal mucosa in seasonal allergic rhinitis. However, there is another potential benefit of applying NoAl (HPMC) along with other commercially available drugs for local treatment of rhinitis, as the formation of a gel layer can substantially delay their clearance from the nose and thus increase their effectiveness. This hypothesis needs to be substantiated clinically.

Detailed description: The main objective of the trial is to test the synergy between HPMC and oxymetazoline (both applied nasally) on the increase of peak nasal inspiratory flow in patients suffering from moderately severe / severe persistent allergic rhinitis.

The design of the trial is parallel-groups, double blind, randomized, placebo controlled, single centre study.

Forty patients are randomly assigned to receive either oxymetazoline followed by HPMC (Group A) or oxymetazoline followed by placebo (Group B).

Each patient is followed up for 15 days. Day 1 is the screening and inclusion visit. Data will then be collected on day 8 \& 15. Patients will fill in diaries their everyday symptoms, adverse events and applied medications.

Eligibility criteria: Inclusion Criteria:

* Male or female patients
* Age ≥ 18 and ≤ 50 years
* Moderately severe / severe persistent allergic rhinitis
* Positive skin prick test for perennial aero-allergens
* Active symptoms with prominent congestion at the time of inclusion

Exclusion Criteria:

* Subjects with pollen sensitization during the respective pollen season
* Subjects with arterial hypertension, arrhythmia or evidence of heart ischemia
* Subjects with other serious chronic comorbidities and bad therapeutic control
* Subjects with nasal polyposis
* Flu-like episode during the past 30 days
* Subjects unable to give informed consent
* Subjects with any of the contra-indications of oxymetazoline or NoAL
* Pregnant or lactating women

Primary outcomes:
measure: Peak nasal inspiratory flow (PNIF) area under the curve (AUC) change between the placebo and active NoAl treatment on day 1
timeFrame: PNIF on Day 1, 8 and 15
Secondary outcomes:
measure: Difference between the PNIF AUC D1-D8 differences between the two groups
timeFrame: PNIF on D1 and D8
measure: Differences in nasal mucociliary clearance (Saccharine test) between both groups.
timeFrame: Performed on D1, D8 and D15
measure: Visual analogue scale (VAS) for the separate rhinitis symptoms between the two groups
timeFrame: On D1, D8 and D15
measure: Change of each symptom score for congestion over 8 days
timeFrame: From D1 to D8
measure: Change of total rhinitis symptom score (TRSS) over 8 days
timeFrame: From D1 to D8
measure: Difference in the applied rescue decongestant (total number of additional puffs of oxymetazoline or any other medications indicated for the treatment of allergic rhinitis) as needed between the two groups
timeFrame: For 15 days
measure: Number and severity of adverse events
timeFrame: 15 days
Other outcomes:
Locations:
city: Sofia
country: Bulgaria
facility: Medical University Sofia, University Hospital "Alexandrovska", Clinic of Allergy and Asthma
Study officials:
affiliation: Medical University Sofia
name: Todor A Popov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tzachev CT, Mandajieva M, Minkov EH, Popov TA. Comparison of the clinical efficacy of standard and mucoadhesive-based nasal decongestants. Br J Clin Pharmacol. 2002 Jan;53(1):107-9. doi: 10.1046/j.0306-5251.2001.01525.x.
citation: Valerieva A, Popov TA, Staevska M, Kralimarkova T, Petkova E, Valerieva E, Mustakov T, Lazarova T, Dimitrov V, Church MK. Effect of micronized cellulose powder on the efficacy of topical oxymetazoline in allergic rhinitis. Allergy Asthma Proc. 2015 Nov-Dec;36(6):e134-9. doi: 10.2500/aap.2015.36.3879. Epub 2015 Jun 29.