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

NCT04115098 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: HSC-MS-19-0677KL2TR003168
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Conditions

Axial Spondyloarthritis

Keywords

spondylitis

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Change in Health Related Quality of Life as Assessed by the Standard Gamble Utility Assessment

  Baseline, 4 weeks

• Change in Health-Related Quality of Life as Assessed by the PROMIS-Preference (PROPr) Score

  Baseline, 4 weeks

• Change in Ability to Perform Tasks as Assessed by the Bath Ankylosing Spondylitis Functional Index (BASFI)

  Baseline, 4 weeks

• Change in Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)

  Baseline, 4 weeks

• Change in Bath Ankylosing Spondylitis Metrology Index (BASMI)

  Baseline, 4 weeks

Study Arms (12)

Celecoxib, Then Meloxicam, Then Naproxen, Then A, Then B

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Celecoxib, Then Meloxicam, Then Naproxen, Then B, Then A

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Celecoxib, Then Naproxen, Then Meloxicam, Then A, Then B

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Celecoxib, Then Naproxen, Then Meloxicam, Then B, Then A

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Meloxicam, Then Celecoxib, Then Naproxen, Then A, Then B

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Meloxicam, Then Celecoxib, Then Naproxen, Then B, Then A

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Meloxicam, Then Naproxen, Then Celecoxib, Then A, Then B

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Meloxicam, Then Naproxen, Then Celecoxib, Then B, Then A

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Naproxen, Then Celecoxib, Then Meloxicam, Then A, Then B

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Naproxen, Then Celecoxib, Then Meloxicam, Then B, Then A

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Naproxen, Then Meloxicam, Then Celecoxib, Then A, Then B

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Naproxen, Then Meloxicam, Then Celecoxib, Then B, Then A

EXPERIMENTAL

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; Drug: Naproxen; Drug: Meloxicam

Interventions

Celecoxib DRUG

Celecoxib 200 mg capsules twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules

Celecoxib, Then Meloxicam, Then Naproxen, Then A, Then B; Celecoxib, Then Meloxicam, Then Naproxen, Then B, Then A; Celecoxib, Then Naproxen, Then Meloxicam, Then A, Then B; Celecoxib, Then Naproxen, Then Meloxicam, Then B, Then A; Meloxicam, Then Celecoxib, Then Naproxen, Then A, Then B; Meloxicam, Then Celecoxib, Then Naproxen, Then B, Then A; Meloxicam, Then Naproxen, Then Celecoxib, Then A, Then B; Meloxicam, Then Naproxen, Then Celecoxib, Then B, Then A; Naproxen, Then Celecoxib, Then Meloxicam, Then A, Then B; Naproxen, Then Celecoxib, Then Meloxicam, Then B, Then A; Naproxen, Then Meloxicam, Then Celecoxib, Then A, Then B; Naproxen, Then Meloxicam, Then Celecoxib, Then B, Then A

Naproxen DRUG

Naproxen 500 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules

Celecoxib, Then Meloxicam, Then Naproxen, Then A, Then B; Celecoxib, Then Meloxicam, Then Naproxen, Then B, Then A; Celecoxib, Then Naproxen, Then Meloxicam, Then A, Then B; Celecoxib, Then Naproxen, Then Meloxicam, Then B, Then A; Meloxicam, Then Celecoxib, Then Naproxen, Then A, Then B; Meloxicam, Then Celecoxib, Then Naproxen, Then B, Then A; Meloxicam, Then Naproxen, Then Celecoxib, Then A, Then B; Meloxicam, Then Naproxen, Then Celecoxib, Then B, Then A; Naproxen, Then Celecoxib, Then Meloxicam, Then A, Then B; Naproxen, Then Celecoxib, Then Meloxicam, Then B, Then A; Naproxen, Then Meloxicam, Then Celecoxib, Then A, Then B; Naproxen, Then Meloxicam, Then Celecoxib, Then B, Then A

Meloxicam DRUG

Meloxicam 7.5 mg tablets twice daily (BID) All 3 medications will be over-encapsulated in identical opaque capsules

Celecoxib, Then Meloxicam, Then Naproxen, Then A, Then B; Celecoxib, Then Meloxicam, Then Naproxen, Then B, Then A; Celecoxib, Then Naproxen, Then Meloxicam, Then A, Then B; Celecoxib, Then Naproxen, Then Meloxicam, Then B, Then A; Meloxicam, Then Celecoxib, Then Naproxen, Then A, Then B; Meloxicam, Then Celecoxib, Then Naproxen, Then B, Then A; Meloxicam, Then Naproxen, Then Celecoxib, Then A, Then B; Meloxicam, Then Naproxen, Then Celecoxib, Then B, Then A; Naproxen, Then Celecoxib, Then Meloxicam, Then A, Then B; Naproxen, Then Celecoxib, Then Meloxicam, Then B, Then A; Naproxen, Then Meloxicam, Then Celecoxib, Then A, Then B; Naproxen, Then Meloxicam, Then Celecoxib, Then B, Then A

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead
• National Center for Advancing Translational Sciences (NCATS): collaborator

Study Sites (1)

The University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Hwang MC, Kim S, Assassi S, Chavez R, Samuel J, Green C, Tyson J, Reveille J. Individualizing NSAID therapy in axial spondyloarthritis: N-of-1 trials with Bayesian analysis. Rheumatology (Oxford). 2025 Dec 1;64(12):6114-6121. doi: 10.1093/rheumatology/keaf393.

  PMID: 40676732 DERIVED

MeSH Terms

Conditions

Axial Spondyloarthritis; Spondylitis

Interventions

Celecoxib; Naproxen; Meloxicam

Condition Hierarchy (Ancestors)

Spondylarthropathies; Spondylarthritis; Spinal Diseases; Bone Diseases; Musculoskeletal Diseases; Ankylosis; Joint Diseases; Arthritis; Bone Diseases, Infectious; Infections

Intervention Hierarchy (Ancestors)

Benzenesulfonamides; Sulfonamides; Amides; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Sulfones; Sulfur Compounds; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Naphthaleneacetic Acids; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Thiazines; Thiazoles

Limitations and Caveats

Terminated due to lack of recruitment

Results Point of Contact

• Title: Mark C. Hwang, MD
• Organization: The University of Texas Health Science Center at Houston

Mark.C.Hwang@uth.tmc.edu

(713) 500-6597

Study Officials

• Mark C Hwang, MD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: October 2, 2019
• First Posted: October 3, 2019
• Study Start: June 25, 2020
• Primary Completion: August 11, 2023
• Study Completion: August 11, 2023
• Last Updated: August 13, 2025
• Results First Posted: September 4, 2024

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)