RhinosinusitisPhase 2NCT01771198
Efficacy Study of SIMVASTATIN to Treat Chronic Rhinosinusitis After Failure of Optimal Treatment
A Phase 2 study testing SIMVASTATIN in people with Rhinosinusitis, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Rhinosinusitis
- What is being tested?
- SIMVASTATIN
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteCanada
- Study dates
- Aug 2012to Jul 2015
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Canada1 site
Centre Hospitalier de l'Université de Montréal (CHUM)
Montreal, Quebec, H2W 1T8
About this study
Official title: Preliminary Evaluation of SIMVASTATIN as an Alternative Anti-inflammatory Agent in Chronic Rhinosinusitis Refractory to Conventional Medical and Surgical Treatment
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.
Read the 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).
- Conditions
- Rhinosinusitis
- Being tested
- SIMVASTATIN
- Keywords
- Chronic rhinosinusitis, Refractory to treatment, SIMVASTATIN
- Medical subject headings
- Rhinosinusitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SIMVASTATINDrug
Also called ZOCOR (trade name), pms-SIMVASTATIN
SIMVASTATIN tablet of 40mg once a day during 30 days
| Study group | Role | What they receive |
|---|---|---|
| SIMVASTATIN 40mg | Experimental | SIMVASTATIN tablet of 40mg once a day during 30 days. Single arm with pre and post treament assessment Receives: Drug: SIMVASTATIN |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sino-Nasal symptomatology
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
Measured: Between Day 30 and Day 60
Secondary outcomes (5)
Bacterial culture
Measured: Between Day 30 and Day 60
Assessemt of liver and kidney functions
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.
Measured: Between Day 0 and Day 60
RNA measurement of inflammatory biomarkers
Total RNA will be extracted from sinus brushing samples.
Measured: Between Day 30 and Day 60
Sinus-Specific Quality of Life (22 questions Sino-nasal outcome test; SNOT-22)
Measured: At Day 0 and Day 30 compared to Day 60 and Day 90
Aspect of sinus mucosa aspect assessed by sinus endoscopy
Assessement of the inflammatory aspect of the sinus mucosa by direct endoscopy of the operated sinus cavities. Grading using the Lund-Kennedy grading system.
Measured: At Day 0 and Day 30 compared to Day 60 and Day 90
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2013 (estimated)
- Study startAug 2012
- Primary completionJul 2015
- Study completionJul 2015
Why it stopped: Lack of efficacy with one month of treatement
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for RhinosinusitisStudies of the same condition, open and under way.
- More trials run by Centre hospitalier de l'Université de Montréal (CHUM)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Responsible party
- Sponsor
- Investigators
- Martin Desrosiers, MD, FRCSC, Principal investigator, Centre hospitalier de l'Université de Montréal (CHUM)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01771198
- Sponsor's protocol ID
- CE11.288
- Other IDs
- Control Number: 156827
- Status last verified
- Aug 2012
- First submitted
- 3 Dec 2012
- Last updated
- 13 Jul 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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 21357906Rezaie-Majd A, Maca T, Bucek RA, Valent P, Muller 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. doi: 10.1161/01.atv.0000022694.16328.cc.
PubMed 12117737McKay 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. doi: 10.4049/jimmunol.172.5.2903.
PubMed 14978092Sakoda 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. doi: 10.1177/154405910608500608.
PubMed 16723648Wang 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 21493317Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995 Oct;167:17-21.
PubMed 7574265
Study at a glance
From the registry record, last updated by the sponsor on 13 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preliminary Evaluation of SIMVASTATIN as an Alternative Anti-inflammatory Agent in Chronic Rhinosinusitis Refractory to Conventional Medical and Surgical Treatment
- ClinicalTrials.gov ID
- NCT01771198
- Acronym / sponsor ID
- CE11.288
- Conditions
- Rhinosinusitis
- Keywords
- Chronic rhinosinusitis, Refractory to treatment, SIMVASTATIN
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of efficacy with one month of treatement
- Enrolment
- 7 participants (actual)
- Lead sponsor
- Centre hospitalier de l'Université de Montréal (CHUM)University, hospital or other
- Collaborators
- Centre de Recherche du Centre Hospitalier de l'Université de Montréal
- Study start
- Aug 2012
- Primary completion
- Jul 2015 (actual)
- Study completion
- Jul 2015 (actual)
- First posted
- 18 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| SIMVASTATIN 40mg | Experimental | Drug: SIMVASTATINSIMVASTATIN tablet of 40mg once a day during 30 days. Single arm with pre and post treament assessment |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
Key exclusion criteria (8 listed)
- Cystic Fibrosis
- Primary immunodeficiencies or documented acquired
- Diabetes
- Taking anticoagulants or bleeding disorders
- Taking oral cortisone within 30 days prior to the inclusion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SIMVASTATINAlso: ZOCOR (trade name), pms-SIMVASTATINSIMVASTATIN tablet of 40mg once a day during 30 days | Drug | SIMVASTATIN 40mg |
Primary outcome
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
5 secondary outcomes
Bacterial culture
Time frame: Between Day 30 and Day 60
Assessemt of liver and kidney functions
Time frame: Between Day 0 and Day 60
RNA measurement of inflammatory biomarkers
Time frame: Between Day 30 and Day 60
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
Aspect of sinus mucosa aspect assessed by sinus endoscopy
Time frame: At Day 0 and Day 30 compared to Day 60 and Day 90
Results and safety
The study was stopped early (reason given: Lack of efficacy with one month of treatement). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jul 2015.
- Background: PubMed 21357906Vaidyanathan 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.
- Background: PubMed 12117737Rezaie-Majd A, Maca T, Bucek RA, Valent P, Muller 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. doi: 10.1161/01.atv.0000022694.16328.cc.
- Background: PubMed 14978092McKay 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. doi: 10.4049/jimmunol.172.5.2903.
- Background: PubMed 16723648Sakoda 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. doi: 10.1177/154405910608500608.
- Background: PubMed 21493317Wang 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.
- Background: PubMed 7574265Lund VJ, Kennedy DW. Quantification for staging sinusitis. The Staging and Therapy Group. Ann Otol Rhinol Laryngol Suppl. 1995 Oct;167:17-21.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Martin Desrosiers, MD, FRCSC principal investigator
Centre hospitalier de l'Université de Montréal (CHUM)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing SIMVASTATIN in people with Rhinosinusitis, run by Centre hospitalier de l'Université de Montréal (CHUM) at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 13 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Lack of efficacy with one month of treatement). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Sino-Nasal symptomatology (time frame: Between Day 30 and Day 60). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01771198, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jul 2015.