Efficacy Study of SIMVASTATIN to Treat Chronic Rhinosinusitis After Failure of Optimal Treatment

Centre hospitalier de l'Université de Montréal (CHUM)

Status and phase

Terminated

Phase 2

Conditions

Rhinosinusitis

Treatments

Drug: SIMVASTATIN

Study type

Interventional

Funder types

Other

Identifiers

NCT01771198

Control Number: 156827 (Other Identifier)

CE11.288

Details and patient eligibility

About

The purpose of this study is to investigate the clinical efficacy of oral treatment with a statin, SIMVASTATIN 40mg, in a target population of patients with severe chronic rhinosinusitis resistant to surgery followed by conventional medical and surgical treatment.

Full description

Visit Day 0 (Screening visit):

Once the consent form is signed by the participant identified as eligible, a blood test for the detection of potential biological contraindications to statins will be done the same day called Day 0. It will include a complete blood count, liver function tests (AST, ALT, GGT, bilirubin, ALP), serum CPK and serum electrolytes for renal function (CREAT, urea). For woman who is capable of having children, a serum pregnancy test will be done. The final inclusion of the subject will be confirmed once the biological results obtained and validated.

The patient will be evaluated by Dr. Desrosiers according to clinical and endoscopic criteria. The participant will have to complete two questionnaires: one questionnaire with questions that assess quality of life (SNOT-22), and another questionnaire on nasal and sinus symptoms.

The subject must comply with an observation period of 30 days during which he/she will pursue only washes the salt water.

Visit Day 30 :

Thirty days after the screening visit, only the subjects with normal results of blood tests, are definitely included and will continue the clinical trial. A clinical and endoscopic sinus exam, a serum pregnancy test will be performed again before the administration of the study drug. Bacterial culture sinus using a swab, and brushing of the sinus mucosa under local anesthesia, will also be performed. Brushing sinus will collect the RNA present in epithelial cells and inflammatory nasal mucosa for the identification of markers of inflammation such as IL6, IL8, IL10, TNF. In addition, the participant must complete again the questionnaire on nasal and sinus symptoms and SNOT-22 questionnaire.

The study medication will consist of taking one tablet of 40mg SIMVASTATIN once a day for 30 days. This visit will be seen as the beginning of treatment (Day 30). The subject will also continue with irrigation of sinus with saline for 30 days until the next visit.

Visit Day 60:

This follow-up visit will take place 4 weeks after the beginning of treatment. A clinical and endoscopic sinus exam, blood collections to assess renal and hepatic function, a bacterial sinus culture, and brushing of sinus mucosa will again be performed. The subject must complete again the questionnaire on nasal and sinus symptoms and SNOT-22 questionnaire.

The participant will continue with irrigation of sinus with saline for 30 days until the next visit.

Visit Day 90:

This follow-up visit will take place 8 weeks after the beginning of treatment. A clinical and endoscopic sinus exam will be done again, and the participant must again complete the questionnaire on nasal and sinus symptoms and SNOT-22 questionnaire.

Statistical analysis:

Each participant is his/her own control. At Day 0, Day 30, Day 60 and Day 90, clinical and endoscopic data will be analyzed using the test Brapkar for the qualitative matched observations which is a generalization of the McNemar test for a number of categories greater than 2.

For each gene (IL6, IL8, IL10, TNF), deltaCt values from the analysis of quantitative PCR (Polymerase Chain Reaction) will be compared before and after treatment with SIMVASTATIN using tests for paired samples: a parametric test (t test) or non-parametric test (Wilcoxon Signed-Rank Test).

Enrollment

7 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Men and women aged between 18 and 65 years.
Chronic rhinosinusitis with or without nasal polyposis requiring functional endoscopic surgery type of bilateral total ethmoidectomy older than six months
Failure (clinical and endoscopic score > 1 on a scale of 3) of conventional treatment after surgery followed by local treatment with corticosteroids and saline irrigation)

Exclusion criteria

Cystic Fibrosis
Primary immunodeficiencies or documented acquired
Diabetes
Taking anticoagulants or bleeding disorders
Taking oral cortisone within 30 days prior to the inclusion
Taking antibiotics within 30 days prior to the inclusion
Sinus or nasal surgery in past six months
Contraindication to statins (pregnancy or lactating; people consuming high quantities of alcohol (3 drinks/day or more), liver disease, severe renal failure, myopathy, hypersensitivity to statins, abnormally elevated transaminase coagulation)