ClinicalTrials.gov

History of Changes for Study: NCT01771198
Efficacy Study of SIMVASTATIN to Treat Chronic Rhinosinusitis After Failure of Optimal Treatment
Latest version (submitted July 9, 2015) on ClinicalTrials.gov
  • A study version is represented by a row in the table.
  • Select two study versions to compare. One each from columns A and B.
  • Choose either the "Merged" or "Side-by-Side" comparison format to specify how the two study versions are to be displayed. The Side-by-Side format only applies to the Protocol section of the study.
  • Click "Compare" to do the comparison and show the differences.
  • Select a version's Submitted Date link to see a rendering of the study for that version.
  • The yellow A/B choices in the table indicate the study versions currently compared below. A yellow table row indicates the study version currently being viewed.
  • Hover over the "Recruitment Status" to see how the study's recruitment status changed.
  • Study edits or deletions are displayed in red.
  • Study additions are displayed in green.
Study Record Versions
Version A B Submitted Date Changes
1 January 16, 2013 None (earliest Version on record)
2 July 9, 2015 Recruitment Status, Study Status, Contacts/Locations and Study Design
Comparison Format:

Scroll up to access the controls

Study NCT01771198
Submitted Date:  January 16, 2013 (v1)

Open or close this module Study Identification
Unique Protocol ID: CE11.288
Brief Title: Efficacy Study of SIMVASTATIN to Treat Chronic Rhinosinusitis After Failure of Optimal Treatment
Official Title: Preliminary Evaluation of SIMVASTATIN as an Alternative Anti-inflammatory Agent in Chronic Rhinosinusitis Refractory to Conventional Medical and Surgical Treatment
Secondary IDs: Control Number: 156827 [Health Canada]
Open or close this module Study Status
Record Verification: August 2012
Overall Status: Recruiting
Study Start: August 2012
Primary Completion: August 2013 [Anticipated]
Study Completion: October 2013 [Anticipated]
First Submitted: December 3, 2012
First Submitted that
Met QC Criteria:
January 16, 2013
First Posted: January 18, 2013 [Estimate]
Last Update Submitted that
Met QC Criteria:
January 16, 2013
Last Update Posted: January 18, 2013 [Estimate]
Open or close this module Sponsor/Collaborators
Sponsor: Centre hospitalier de l'Université de Montréal (CHUM)
Responsible Party: Sponsor
Collaborators: Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Open or close this module Oversight
U.S. FDA-regulated Drug:
U.S. FDA-regulated Device:
Data Monitoring: No
Open or close this module Study Description
Brief Summary: 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.
Detailed 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).

Open or close this module Conditions
Conditions: Rhinosinusitis
Keywords: Chronic rhinosinusitis
Refractory to treatment
SIMVASTATIN
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 20 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: SIMVASTATIN 40mg
SIMVASTATIN tablet of 40mg once a day during 30 days. Single arm with pre and post treament assessment
Drug: SIMVASTATIN
SIMVASTATIN tablet of 40mg once a day during 30 days
Other Names:
  • ZOCOR (trade name)
  • pms-SIMVASTATIN
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Sino-Nasal symptomatology
[ Time Frame: Between Day 30 and Day 60 ]

Day 0: Day of recruitment/screening; Day 30: Thirty days after recruitment, day of enrollment of subjects with normal hepatic and renal blood tests, and initiation of SIMVASTATIN 40mg once a day during 30 days; Day 60: Thirty days after Day 30, end of treatment administration; Day 90: Thirty days after Day 60, follow-up visit
Secondary Outcome Measures:
1. Bacterial culture
[ Time Frame: Between Day 30 and Day 60 ]

2. Assessemt of liver and kidney functions
[ Time Frame: Between Day 0 and Day 60 ]

Alterations in hepatic and renal functions will be assessed at screening to exclude indivudals with pre-existing disturbances. These will be repated at day 60 of treatment to monitor potential treatment-related effects.
3. RNA measurement of inflammatory biomarkers
[ Time Frame: Between Day 30 and Day 60 ]

Total RNA will be extracted from sinus brushing samples.
4. Sinus-Specific Quality of Life (22 questions Sino-nasal outcome test; SNOT-22)
[ Time Frame: At Day 0 and Day 30 compared to Day 60 and Day 90 ]

5. Aspect of sinus mucosa aspect assessed by sinus endoscopy
[ Time Frame: At Day 0 and Day 30 compared to Day 60 and Day 90 ]

Assessement of the inflammatory aspect of the sinus mucosa by direct endoscopy of the operated sinus cavities. Grading using the Lund-Kennedy grading system.
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 65 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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)
Open or close this module Contacts/Locations
Central Contact Person: Leandra Mfuna Endam, MSc
Telephone: 514-890-8000 Ext. 14170
Email: leandra.mfuna-endam.chum@ssss.gouv.qc.ca
Central Contact Backup: Martin Desrosiers, MD, FRCSC
Telephone: 514-890-8444
Email: desrosiers_martin@hotmail.com
Study Officials: Martin Desrosiers, MD, FRCSC
Principal Investigator
Centre hospitalier de l'Université de Montréal (CHUM)
Locations: Canada, Quebec
Centre Hospitalier de l'Université de Montréal (CHUM)
[Recruiting]
Montreal, Quebec, Canada, H2W 1T8
Contact:Contact: Leandra Mfuna Endam, MSc 514-890-8000 Ext. 14170 leandra.mfuna-endam.chum@ssss.gouv.qc.ca
Contact:Contact: Martin Desrosiers, MD, FRCSC 514-890-8444 desrosiers_martin@hotmail.com
Contact:Principal Investigator: Martin Desrosiers, MD, FRCSC
Open or close this module IPDSharing
Plan to Share IPD:
Open or close this module References
Citations: Vaidyanathan S, Barnes M, Williamson P, Hopkinson P, Donnan PT, Lipworth B. Treatment of chronic rhinosinusitis with nasal polyposis with oral steroids followed by topical steroids: a randomized trial. Ann Intern Med. 2011 Mar 1;154(5):293-302. doi: 10.7326/0003-4819-154-5-201103010-00003. PubMed 21357906
Rezaie-Majd A, Maca T, Bucek RA, Valent P, Müller MR, Husslein P, Kashanipour A, Minar E, Baghestanian M. Simvastatin reduces expression of cytokines interleukin-6, interleukin-8, and monocyte chemoattractant protein-1 in circulating monocytes from hypercholesterolemic patients. Arterioscler Thromb Vasc Biol. 2002 Jul 1;22(7):1194-9. PubMed 12117737
McKay A, Leung BP, McInnes IB, Thomson NC, Liew FY. A novel anti-inflammatory role of simvastatin in a murine model of allergic asthma. J Immunol. 2004 Mar 1;172(5):2903-8. PubMed 14978092
Sakoda K, Yamamoto M, Negishi Y, Liao JK, Node K, Izumi Y. Simvastatin decreases IL-6 and IL-8 production in epithelial cells. J Dent Res. 2006 Jun;85(6):520-3. PubMed 16723648
Wang W, Le W, Ahuja R, Cho DY, Hwang PH, Upadhyay D. Inhibition of inflammatory mediators: role of statins in airway inflammation. Otolaryngol Head Neck Surg. 2011 Jun;144(6):982-7. doi: 10.1177/0194599811400367. Epub 2011 Apr 5. PubMed 21493317
Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995 Oct;167:17-21. PubMed 7574265
Links:
Available IPD/Information:

Scroll up to access the controls Scroll to the Study top

U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services