Individualizing Anti-Inflammatory Medications for Adults With Axial Spondyloarthritis: A Series of N-of 1 Trials

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to compare selective cyclooxygenase-2 (COX-2) and non selective COX inhibitors with respect to the extent to which disease activity is improved without self reported, unacceptable side effects among individual patients with axial spondyloarthritis (AxSpA),to compare selective COX-2 and nonselective COX inhibitors impact on Health related Quality of Life (HrQOL) and how this relates to changes in disease activity and to conduct proteomic assessment of predictive biomarkers of non steroidal anti-inflammatory drug(NSAID) response

Official Title
-----------------
Individualizing Anti-Inflammatory Medications for Adults With Axial Spondyloarthritis: A Series of N-of 1 Trials

Conditions
-----------------
Axial Spondyloarthritis

Intervention / Treatment
-----------------
* Drug: Drug order 1
* Drug: Drug order 2
* Drug: Drug order 3
* Drug: Drug order 4
* Drug: Drug order 5
* Drug: Drug order 6


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must meet modified New York Classification and/or Assessment of Spondyloarthritis International Society (ASAS) criteria for Classification Criteria for AxSpA Ankylosing Spondylitis Disease Activity Score greater than or equal to 2.1. Exclusion Criteria: Changing background biologic/disease modifying-rheumatic medications within less than 3 months. Opioid medication use Current or expected pregnancy History of cardiovascular disease (previous stroke, myocardial infarction, or percutaneous intervention. End stage liver disease Chronic Kidney Disease greater than Stage IIIb

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug order 1<br> | Drug: Drug order 1<br>* each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, ACB, BAC, BCA, CBA, CAB) of the following three drugs: Naproxen 500 mg tablets twice daily (BID), Meloxicam 7.5 mg tablets BID and Celecoxib 200 mg capsules BID. Patients will be randomized in blocks of 6 to ensure that no drug is assigned to be the first drug tested more often than the others. Medications will be obtained by the investigation team, and then all 3 medications will be overencapsulated in identical opaque capsules.<br>|
| Experimental: Drug order 2<br> | Drug: Drug order 2<br>* each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, ACB, BAC, BCA, CBA, CAB) of the following three drugs: Naproxen 500 mg tablets twice daily (BID), Meloxicam 7.5 mg tablets BID and Celecoxib 200 mg capsules BID. Patients will be randomized in blocks of 6 to ensure that no drug is assigned to be the first drug tested more often than the others. Medications will be obtained by the investigation team, and then all 3 medications will be overencapsulated in identical opaque capsules.<br>|
| Experimental: Drug order 3<br> | Drug: Drug order 3<br>* each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, ACB, BAC, BCA, CBA, CAB) of the following three drugs: Naproxen 500 mg tablets twice daily (BID), Meloxicam 7.5 mg tablets BID and Celecoxib 200 mg capsules BID. Patients will be randomized in blocks of 6 to ensure that no drug is assigned to be the first drug tested more often than the others. Medications will be obtained by the investigation team, and then all 3 medications will be overencapsulated in identical opaque capsules.<br>|
| Experimental: Drug order 4<br> | Drug: Drug order 4<br>* each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, ACB, BAC, BCA, CBA, CAB) of the following three drugs: Naproxen 500 mg tablets twice daily (BID), Meloxicam 7.5 mg tablets BID and Celecoxib 200 mg capsules BID. Patients will be randomized in blocks of 6 to ensure that no drug is assigned to be the first drug tested more often than the others. Medications will be obtained by the investigation team, and then all 3 medications will be overencapsulated in identical opaque capsules.<br>|
| Experimental: Drug order 5<br> | Drug: Drug order 5<br>* each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, ACB, BAC, BCA, CBA, CAB) of the following three drugs: Naproxen 500 mg tablets twice daily (BID), Meloxicam 7.5 mg tablets BID and Celecoxib 200 mg capsules BID. Patients will be randomized in blocks of 6 to ensure that no drug is assigned to be the first drug tested more often than the others. Medications will be obtained by the investigation team, and then all 3 medications will be overencapsulated in identical opaque capsules.<br>|
| Experimental: Drug order 6<br> | Drug: Drug order 6<br>* each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, ACB, BAC, BCA, CBA, CAB) of the following three drugs: Naproxen 500 mg tablets twice daily (BID), Meloxicam 7.5 mg tablets BID and Celecoxib 200 mg capsules BID. Patients will be randomized in blocks of 6 to ensure that no drug is assigned to be the first drug tested more often than the others. Medications will be obtained by the investigation team, and then all 3 medications will be overencapsulated in identical opaque capsules.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Baseline | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 1,week 5 | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 2,week 9 | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 3,week 13 | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 4,week 17 | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 5,week 21 | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 6,week 25 | 
| Extent of disease activity as measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS) | The ASDAS score ranges from 0-10 with a higher score meaning worse disease activity. | Visit 7,week 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | baseline,week 1 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 1,week 5 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 2,week 9 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 3,week 13 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 4,week 17 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 5,week 21 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 6,week 25 | 
| Health related quality of life as assessed by the Standard Gamble Utility assessment | The Standard Gamble Utility assessment is scored between 0-1,0 being worst outcome and 1 being best outcome | Visit 7,week 29 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Baseline,Week 1 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 1,week 5 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 2,week 9 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 3,week 13 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 4,week 17 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 5,week 21 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 6,week 25 | 
| Patient-Information Measurement Information System (PROMIS-29) | The PROMIS-29 has 29 questions which are each scored form 1-5,1 being unable to do and 5 being able to do without difficulty | Visit 7,week 29 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Baseline,Week1 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 1,week 5 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 2,week 9 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 3,week 13 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 4,week 17 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 5,week 21 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 6,week 25 | 
| Change in ability to perform tasks as assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI) | BASFI score ranges form 0-10, 0 being easy and 10 being impossible | Visit 7,week 29 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Baseline,Week1 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 1,week 5 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 2,week 9 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 3,week 13 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 4,week 17 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 5,week 21 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 6,week 25 | 
| Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), | The BASDAI consists of a 0 - 10 scale measuring discomfort, pain, and fatigue (0 being no problem and 10 being the worst problem) | Visit 7,week 29 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | Baseline,Week1 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | Visit 1,week 5 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | Visit 2, week 9 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | Visit 3,week 13 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | Visit 4,week 17 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | Visit 5,week 21 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | visit 6,week 25 | 
| Bath Ankylosing Spondylitis Metrology Index (BASMI) | BASMI score of 0-10 is calculated.The higher the BASMI score the more severe the patient's limitation of movement due to their ankylosing spondylitis | visit 7,week 29 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Baseline,Week 1 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 1,Week 5 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 2,Week 9 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 3,Week13 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 4,Week17 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 5,Week 21 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 6,Week 25 | 
| Change in pain as assessed by the Visual Analog Scale-Pain (VAS-Pain) | The VAS Pain is scored form 0-10 0 being no pain and 10 being unbearable pain | Visit 7,Week 29 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Baseline,week1 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit1,week5 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit2,week9 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit 3,week 13 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit 4,week 17 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit 5,week 21 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit 6,week 25 | 
| Visual Analog Scale-Global VAS-Global | The VAS-Global is scored form 0-10 0 being not active and 10 being very active | Visit 7,week 29 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
spondylitis