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

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

Study Overview

• Status: Terminated
• Conditions: Axial Spondyloarthritis
• Intervention / Treatment: Drug: Celecoxib; Drug: Naproxen; Drug: Meloxicam

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • The University of Texas Health Science Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Celecoxib, Then Meloxicam, Then Naproxen, Then A, Then B; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Celecoxib, Then Meloxicam, Then Naproxen, Then B, Then A; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Celecoxib, Then Naproxen, Then Meloxicam, Then A, Then B; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Celecoxib, Then Naproxen, Then Meloxicam, Then B, Then A; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Meloxicam, Then Celecoxib, Then Naproxen, Then A, Then B; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Meloxicam, Then Celecoxib, Then Naproxen, Then B, Then A; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Meloxicam, Then Naproxen, Then Celecoxib, Then A, Then B; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Meloxicam, Then Naproxen, Then Celecoxib, Then B, Then A; Each participant will be randomized to a different initial drug sequence (6 possibilities: ABC, 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Naproxen, Then Celecoxib, Then Meloxicam, Then A, Then B; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Naproxen, Then Celecoxib, Then Meloxicam, Then B, Then A; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Naproxen, Then Meloxicam, Then Celecoxib, Then A, Then B; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules
Experimental: Naproxen, Then Meloxicam, Then Celecoxib, Then B, Then A; 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. After these 3 initial treatment sessions, participants are then randomized to the 2 best-performing drugs for 2 additional treatment sessions [randomized to either alphabetical order (A then B) or reverse alphabetical order (B then A)] There will be no washout periods. All 3 medications will be over-encapsulated in identical opaque capsules.	Drug: Celecoxib; Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Naproxen; Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules; Drug: Meloxicam; Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Disease Activity as Measured by the Ankylosing Spondylitis Disease Activity Score (ASDAS)	The ASDAS total score ranges from 0-10, with a higher score meaning worse disease activity. The change in score is reported as [(ASDAS score at baseline) - (ASDAS score at 4 weeks)]--a positive value indicates that the score (and disease activity) decreased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Bath Ankylosing Spondylitis Metrology Index (BASMI)	BASMI total score ranges from 0 - 10.The higher the BASMI score, the more severe the patient's limitation of movement due to their ankylosing spondylitis. The change in score is reported as [(BASMI score at baseline) - (BASMI score at 4 weeks)]--a positive value indicates that the score (and limitation of movement) decreased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks
Change in Health Related Quality of Life as Assessed by the Standard Gamble Utility Assessment	The Standard Gamble Utility assessment is scored between 0-1, with 0 being the worst outcome and 1 being the best outcome. The change in score is reported as [(Standard Gamble score at baseline) - (Standard Gamble score at 4 weeks)]--a negative value indicates that the Health Related Quality of Life increased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval.	Baseline, 4 weeks
Change in Health-Related Quality of Life as Assessed by the PROMIS-Preference (PROPr) Score	The reported Patient-Reported Outcomes Measurement Information System-Preference (PROPr) Score ranges from 0 to 1, with 0 being the worst outcome and 1 being the best outcome. The change in score is reported as [(PROPr score at baseline) - (PROPR score at 4 weeks)] - a negative value indicates that the person's Health Related Quality of Life increased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks
Change in Ability to Perform Tasks as Assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI)	BASFI score ranges from 0-10, with 0 being easy and 10 being impossible. The change in score is reported as [(BASFI score at baseline) - (BASFI score at 4 weeks)], and a positive value indicates that the score (and difficulty with tasks) decreased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks
Change in 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). The change in score is reported as [(BASDAI score at baseline) - (BASDAI score at 4 weeks)] -- a positive value indicates that the score (and disease activity) decreased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks
Change in Pain as Assessed by the Visual Analog Scale-Pain (VAS-Pain)	The VAS-Pain total score is 0 - 100, with 0 being no pain and 100 being unbearable pain. The change in score is reported as [(VAS- Pain score at baseline) - (VAS- Pain score at 4 weeks)] --a positive value indicates that the score (and pain level) decreased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks
Change in Visual Analog Scale-Global (VAS-Global)	The VAS-Global is scored from 0-100, with 0 being not active and 100 being very active. The change in score is reported as [(VAS- Global score at baseline) - (VAS- Global score at 4 weeks)] --a negative value indicates that the score (and activity level) increased over time. The "Measure of Dispersion/Precision" indicated as "95% Confidence Interval" actually refers to a "95% Credible Interval."	Baseline, 4 weeks

Collaborators and Investigators

• Sponsor: The University of Texas Health Science Center, Houston
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Mark C Hwang, MD, The University of Texas Health Science Center, Houston

Study record dates

Study Major Dates

• Study Start (Actual): June 25, 2020
• Primary Completion (Actual): August 11, 2023
• Study Completion (Actual): August 11, 2023

Study Registration Dates

• First Submitted: October 2, 2019
• First Submitted That Met QC Criteria: October 2, 2019
• First Posted (Actual): October 3, 2019

Study Record Updates

• Last Update Posted (Actual): August 13, 2025
• Last Update Submitted That Met QC Criteria: August 8, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: spondylitis
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Arthritis; Joint Diseases; Infections; Bone Diseases, Infectious; Spinal Diseases; Spondylarthropathies; Ankylosis; Axial Spondyloarthritis; Spondylitis; Spondylarthritis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Gout Suppressants; Antirheumatic Agents; Sensory System Agents; Analgesics, Non-Narcotic; Analgesics; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Cyclooxygenase 2 Inhibitors; Celecoxib; Meloxicam; Naproxen
• Other Study ID Numbers: HSC-MS-19-0677; KL2TR003168 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No